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Här samlar vi ett antal av de vetenskapliga artiklar som CPF:s forskare har publicerat 2017. Listorna baseras på bibliometrisökningar i databasen PubMed och är därför inte fullständiga och kan innehålla fel. Samtliga länkar leder till PubMed.
Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples. An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
Gray matter; Mega-analysis; Social anxiety disorder; Striatum; Structural MRI; Voxel-based morphometry
Child anxiety disorders are highly prevalent and cause significant impairment. Cognitive behavioral therapy (CBT) is recommended for child anxiety disorders, but access to CBT is limited, particularly in rural areas. Internet-delivered CBT (ICBT) can help increase the availability of evidence-based interventions and evidence is beginning to accumulate to indicate that ICBT is efficacious for children with anxiety disorders. However, whether the results of controlled trials are transferrable to real-world clinical settings is unclear. The objective of this study was to evaluate whether therapist-guided ICBT is feasible and potentially effective when implemented in an outpatient clinic in rural Sweden. Children (N = 19) aged 8-12 with anxiety disorders underwent a 12-week ICBT program called BiP Anxiety. Feasibility measures included treatment satisfaction, compliance and feedback from clinicians. Clinical outcome measures were clinician-, parent- and child ratings of anxiety symptoms and functional impairment. Overall, participants and clinicians were satisfied with the treatment content and format. There were statistically significant changes from pre- to post-treatment on the primary outcome measure (t = - 4.371, p < 0.001), as well as on all secondary outcome measures. Therapeutic gains were maintained for up to three months from the post-treatment assessment. At follow-up, 68% were no longer in need of treatment and could be discharged from the clinic. The study suggests the feasibility of implementing ICBT in regular health care. Implementation of ICBT could dramatically increase access to evidence based treatment for children with anxiety disorders who live far away from specialist clinics.
Anxiety disorders; Behavior therapy; Child; Implementation; Rural health services; eHealth
Fully automated self-help interventions can serve as highly cost-effective mental health promotion tools for massive amounts of people. However, these interventions are often characterised by poor adherence. One way to address this problem is to mimic therapy support by a conversational agent. The objectives of this study were to assess the effectiveness and adherence of a smartphone app, delivering strategies used in positive psychology and CBT interventions via an automated chatbot (Shim) for a non-clinical population - as well as to explore participants' views and experiences of interacting with this chatbot. A total of 28 participants were randomized to either receive the chatbot intervention (n = 14) or to a wait-list control group (n = 14). Findings revealed that participants who adhered to the intervention (n = 13) showed significant interaction effects of group and time on psychological well-being (FS) and perceived stress (PSS-10) compared to the wait-list control group, with small to large between effect sizes (Cohen's d range 0.14-1.06). Also, the participants showed high engagement during the 2-week long intervention, with an average open app ratio of 17.71 times for the whole period. This is higher compared to other studies on fully automated interventions claiming to be highly engaging, such as Woebot and the Panoply app. The qualitative data revealed sub-themes which, to our knowledge, have not been found previously, such as the moderating format of the chatbot. The results of this study, in particular the good adherence rate, validated the usefulness of replicating this study in the future with a larger sample size and an active control group. This is important, as the search for fully automated, yet highly engaging and effective digital self-help interventions for promoting mental health is crucial for the public health.
As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.
machine learning; quality control; shape analysis
Obsessive-compulsive disorder (OCD) is associated with increased mortality, but the causes of this increase are poorly understood. This study examined whether OCD is associated with an increased risk of metabolic and cardiovascular complications.
Individuals diagnosed with OCD (n = 25,415) were identified from a cohort of 12,497,002 individuals living in Sweden between 1973 and 2013. Cox proportional hazard regression analyses were used to investigate the risk of metabolic and cardiovascular complications in OCD patients compared with the general population and unaffected full siblings of OCD individuals. Exploratory analyses were used to examine the effect of treatment with serotonin reuptake inhibitors, with or without antipsychotics, on the outcomes of interest.
Individuals with OCD had a higher risk of any metabolic or cardiovascular complications compared with the general population (adjusted hazard ratio = 1.45; 95% confidence interval = 1.42-1.49) and their unaffected full siblings (adjusted hazard ratio = 1.47; 95% confidence interval = 1.40-1.54). In the fully adjusted sibling comparison models, patients had higher risks of obesity, type 2 diabetes mellitus, and circulatory system diseases. The risks were already evident from the beginning of the follow-up period and remained largely unchanged when excluding different groups of psychiatric comorbidities. Compared with patients who were not taking serotonin reuptake inhibitors, patients taking higher doses of serotonin reuptake inhibitors and who had a longer duration of treatment had significantly lower risks of metabolic and cardiovascular complications, regardless of whether they were also taking antipsychotics.
OCD is associated with an increased risk of metabolic and cardiovascular complications. Our results underscore the importance of carefully monitoring metabolic and cardiovascular health in patients with OCD early in the course of the disorder.
Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Antidepressants; Antipsychotics; Cardiovascular complications; Metabolic syndrome; Neuroleptics; Serotonin reuptake inhibitors
Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.
We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls).
Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15).
Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.
Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ADHD; Epidemiology; GWAS; Neurodevelopmental disorders; Polygenic risk score analysis; Sex bias
Nonsuicidal self-injury (NSSI) is a serious health risk behavior that forms the basis of a tentative diagnosis in DSM-5, NSSI Disorder (NSSID). To date, established treatments specific to NSSI or NSSID are scarce. As a first step in evaluating the feasibility, acceptability, and utility of a novel treatment for adolescents with NSSID, we conducted an open trial of emotion regulation individual therapy for adolescents (ERITA): a 12-week, behavioral treatment aimed at directly targeting both NSSI and its proposed underlying mechanism of emotion regulation difficulties.
Seventeen girls (aged 13-17; mean = 15.31) with NSSID were enrolled in a study adopting an uncontrolled open trial design with self-report and clinician-rated assessments of NSSI and other self-destructive behaviors, emotion regulation difficulties, borderline personality features, and global functioning administered at pre-treatment, post-treatment, and 6-month follow-up. Measures of NSSI and emotion regulation difficulties were also administered weekly during treatment.
Ratings of treatment credibility and expectancy and the treatment completion rate (88%) were satisfactory, and both therapeutic alliance and treatment attendance were strong. Intent-to-treat analyses revealed significant improvements associated with large effect sizes in past-month NSSI frequency, emotion regulation difficulties, self-destructive behaviors, and global functioning, as well as a medium effect size in past-month NSSI versatility, from pre- to post-treatment. Further, all of these improvements were either maintained or further improved upon at 6-month follow-up. Finally, change in emotion regulation difficulties mediated improvements in NSSI over the course of treatment.
Results suggest the acceptability, feasibility, and utility of this treatment for adolescents with NSSID.
ClinicalTrials.gov (NCT02326012, December 22, 2014, retrospectively registered).
Emotion regulation; Emotion regulation individual therapy; Mediation; Nonsuicidal self-injury disorder; Self-harm
The evidence base to assess the efficacy and effectiveness of alcohol brief interventions (ABI) is weakened by variation in the outcomes measured and by inconsistent reporting. The 'Outcome Reporting in Brief Intervention Trials: Alcohol' (ORBITAL) project aims to develop a core outcome set (COS) and reporting guidance for its use in future trials of ABI in a range of settings.
An international Special Interest Group was convened through INEBRIA (International Network on Brief Interventions for Alcohol and Other Drugs) to inform the development of a COS for trials of ABI. ORBITAL will incorporate a systematic review to map outcomes used in efficacy and effectiveness trials of ABI and their measurement properties, using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. This will support a multi-round Delphi study to prioritise outcomes. Delphi panellists will be drawn from a range of settings and stakeholder groups, and the Delphi study will also be used to determine if a single COS is relevant for all settings. A consensus meeting with key stakeholder representation will determine the final COS and associated guidance for its use in trials of ABI.
ORBITAL will develop a COS for alcohol screening and brief intervention trials, with outcomes stratified into domains and guidance on outcome measurement instruments. The standardisation of ABI outcomes and their measurement will support the ongoing development of ABI studies and a systematic synthesis of emerging research findings. We will track the extent to which the COS delivers on this promise through an exploration of the use of the guidance in the decade following COS publication.
Alcohol; Alcohol brief intervention; Brief intervention; Consensus methods; Core outcome set; Delphi technique; Measurement; Outcomes standardisation; Screening; Trial
Alcohol intoxication among spectators at sporting events and related problems, such as violence, are of great concern in many countries around the world. However, knowledge is scarce about whether or not alcohol is served to obviously intoxicated spectators at licensed premises inside and outside the sporting arenas, and if obviously intoxicated spectators are allowed entrance to these events. The objective of this study was therefore to examine the occurrences of overserving at licensed premises inside and outside arenas, and of allowed entry of obviously intoxicated spectators into arenas.
An observational study assessing the rate of denied alcohol service and denied entry to arenas of trained professional actors portraying a standardized scene of obvious alcohol intoxication (i.e., pseudo-patrons) was conducted. The scene was developed by an expert panel, and each attempt was monitored by an observer. The settings were 2 arenas hosting matches in the Swedish Premier Football League in the largest city in Sweden and 1 arena in the second largest city, including entrances and licensed premises inside and outside the arenas.
The rates of denied alcohol service were 66.9% at licensed premises outside the arenas (n = 151) and 24.9% at premises inside the arenas (n = 237). The rate of denied entry to the arenas (n = 102) was 10.8%.
Overserving and allowed entry of obviously alcohol-intoxicated spectators are problematic at sporting events in Sweden and may contribute to high overall intoxication levels among spectators. The differences in server intervention rates indicate that serving staff at licensed premises inside the arenas and entrance staff are not likely to have been trained in responsible beverage service. This result underscores the need for server training among staff at the arenas.
Copyright © 2017 by the Research Society on Alcoholism.
Alcohol Prevention; Community-Based Intervention; Football; Pseudo-Patron; Sporting Events
Social anxiety disorder (SAD) is one of the most common psychiatric disorders in youth, with a prevalence of about 3%-4% and increased risk of adverse long-term outcomes, such as depression. Cognitive-behavioural therapy (CBT) is considered the first-line treatment for youth with SAD, but many adolescents remain untreated due to limited accessibility to CBT. The aim of this study was to develop and evaluate the feasibility and preliminary efficacy of a therapist-guided internet-delivered CBT treatment, supplemented with clinic-based group exposure sessions (BIP SOFT).
A proof-of-concept, open clinical trial with 6-month follow-up.
The trial was conducted at a child and adolescent psychiatric research clinic, and participants (n=30) were 13-17 years old (83% girls) with a principal diagnosis of SAD.
12 weeks of intervention, consisting of nine remote therapist-guided internet-delivered CBT sessions and three group exposure sessions at the clinic for the adolescents and five internet-delivered sessions for the parents.
Adolescents were generally satisfied with the treatment, and the completion rate of internet modules, as well as attendance at group sessions, was high. Post-treatment assessment showed a significant decrease in clinician-rated, adolescent-rated and parent-rated social anxiety (d=1.17, 0.85 and 0.79, respectively), as well as in general self-rated and parent-rated anxiety and depression (d=0.76 and 0.51), compared with pretreatment levels. Furthermore, 47% of participants no longer met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for SAD at post-treatment. At a 6-month follow-up, symptom reductions were maintained, or further improved, and 57% of participants no longer met criteria for SAD.
Therapist-guided and parent-guided internet-delivered CBT, supplemented with a limited number of group exposure sessions, is a feasible and promising intervention for adolescents with SAD.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
anxiety disorders; mental health
This is the third in a series of four empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Autism Spectrum Disorder (ASD). The present study aimed to describe functioning in ASD (as operationalized by the ICF) derived from the perspectives of diagnosed individuals, family members, and professionals. A qualitative study using focus groups and semi-structured interviews were conducted with 19 stakeholder groups (N = 90) from Canada, India, Saudi Arabia, South Africa, and Sweden. Meaningful concepts from the focus groups and individual interviews were linked to ICF categories using a deductive qualitative approach with standardized linking procedures. The deductive qualitative content analysis yielded meaningful functioning concepts that were linked to 110 ICF categories across all four ICF components. Broad variation of environmental factors and activities and participation categories were identified in this study, while body functions consisted mainly of mental functions. Body structures were sparsely mentioned by the participants. Positive aspects of ASD included honesty, attention to detail, and memory. The experiences provided by international stakeholders support the need to understand individuals with ASD in a broader perspective, extending beyond diagnostic criteria into many areas of functioning and environmental domains. This study is part of a larger systematic effort that will provide the basis to define ICF Core Sets for ASD, from which assessment tools can be generated for use in clinical practice, research, and health care policy making. Autism Res 2018, 11: 463-475. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.
The study findings support the need to understand the living experiences of individuals with Autism Spectrum Disorder (ASD) from a broader perspective, taking into account many areas of an individual's functioning and environment. The ICF can serve as foundation for exploring these living experiences more extensively by offering tools that enable wide variety of individual difficulties and strengths to be captured along with important environmental influences. As such, these tools can facilitate interventions that meet the needs and goals of the individual.
© 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.
ICF; assessment; autism spectrum disorder; clinical practice; functioning; qualitative study; strength
The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a widespread measure of disability and functional impairment, which is bundled with the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) for use in psychiatry. Administering psychometric scales via the Internet is an effective way to reach respondents and allow for convenient handling of data.
The aim was to study the psychometric properties of the 12-item self-report WHODAS 2.0 when administered online to individuals with anxiety and stress disorders. The WHODAS 2.0 was hypothesized to exhibit high internal consistency and be unidimensional. We also expected the WHODAS 2.0 to show high 2-week test-retest reliability, convergent validity (correlations approximately .50 to .90 with other self-report measures of functional impairment), that it would differentiate between patients with and without exhaustion disorder, and that it would respond to change in primary symptom domain.
We administered the 12-item self-report WHODAS 2.0 online to patients with anxiety and stress disorders (N=160) enrolled in clinical trials of cognitive behavior therapy, and analyzed psychometric properties within a classical test theory framework. Scores were compared with well-established symptom and disability measures, and sensitivity to change was studied from pretreatment to posttreatment assessment.
The 12-item self-report WHODAS 2.0 showed high internal consistency (Cronbach alpha=.83-.92), high 2-week test-retest reliability (intraclass correlation coefficient=.83), adequate construct validity, and was sensitive to change. We found preliminary evidence for a three-factorial structure, but one strong factor accounted for a clear majority of the variance.
We conclude that the 12-item self-report WHODAS 2.0 is a psychometrically sound instrument when administered online to individuals with anxiety and stress disorders, but that it is probably fruitful to also report the three subfactors to facilitate comparisons between studies.
Clinicaltrials.gov NCT02540317; https://clinicaltrials.gov/ct2/show/NCT02540317 (Archived by WebCite at http://www.webcitation.org/6vQEdYAem); Clinicaltrials.gov NCT02314065; https://clinicaltrials.gov/ct2/show/NCT02314065 (Archived by WebCite at http://www.webcitation.org/6vQEjlUU8).
©Erland Axelsson, Elin Lindsäter, Brjánn Ljótsson, Erik Andersson, Erik Hedman-Lagerlöf. Originally published in JMIR Mental Health (http://mental.jmir.org), 08.12.2017.
Internet; WHODAS; disability; psychometrics; questionnaire; validity
Minor physical anomalies (MPAs) are subtle anatomical deviations in one's appearance and may suggest altered embryogenesis. MPAs have been shown to be more common in neurodevelopmental disorders (NDDs) compared with typical development. Still, further studies are needed on MPAs in NDDs, especially using twins to adjust for confounding familial factors.
Clinical assessments were conducted on 116 twins (61 NDD, 55 controls) from 51 monozygotic and 7 dizygotic pairs to examine MPAs and their association with DSM-5 defined NDDs. Additionally, the relationship between the number of MPAs within twins by zygosity was investigated.
Within the cohort sample, a specific association was found between MPAs and autism spectrum disorder (ASD) diagnosis (crude odds ratio = 1.29, p = .047; adjusted odds ratios = 1.26-1.33, adjusted p values = .032-.073) and autistic traits (crude β = 3.02, p = .002; adjusted β = 2.28, p = .019), but not NDDs in general or ADHD, nor within-pairs. Identified MPAs in ASD included overweight, hypermobility, pes planus, straight eyebrows, vision impairment, arachnodactyly/long toes, long eyelashes, and microtia. The number of MPAs within all monozygotic pairs was highly correlated (r = .88, p < .001).
MPAs are more frequent in participants with ASD and may be influenced by genetics. The value of MPAs for (early) detection should be further explored, as they might index individuals at increased risk for ASD in particular.
ADHD; ASD; Autism; Minor physical anomalies; Neurodevelopmental disorders
GPR44 expression has recently been described as highly β-cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes. A radiolabeled small-molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of β-cells in pigs and nonhuman primates by positron emission tomography as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from subjects without and with diabetes, in combination with insulin staining, was performed to assess β-cell selectivity of the radiotracer. Proof of principle of in vivo targeting of human islets by [11C]AZ12204657 was shown in the immunodeficient mouse transplantation model. Furthermore, [11C]AZ12204657 bound by a GPR44-mediated mechanism in pancreatic sections from humans and pigs without diabetes, but not those with diabetes. In vivo [11C]AZ12204657 bound specifically to GPR44 in pancreas and spleen and could be competed away dose-dependently in nondiabetic pigs and nonhuman primates. [11C]AZ12204657 is a first-in-class surrogate imaging biomarker for pancreatic β-cells by targeting the protein GPR44.
A 25% reduction of weekly work hours for full-time employees has been shown to improve sleep and alertness and reduce stress during both workdays and days off. The aim of the present study was to investigate how employees use their time during such an intervention: does total workload (paid and non-paid work) decrease, and recovery time increase, when work hours are reduced?
Full-time employees within the public sector (n=636; 75% women) were randomised into intervention group and control group. The intervention group (n=370) reduced worktime to 75% with preserved salary during 18 months. Data were collected at baseline, after 9 months and 18 months. Time-use was reported every half-hour daily between 06:00 and 01:00 during 1 week at each data collection. Data were analysed with multilevel mixed modelling.
Compared with the control group, the intervention group increased the time spent on domestic work and relaxing hobby activities during workdays when worktime was reduced (P≤0.001). On days off, more time was spent in free-time activities (P=0.003). Total workload decreased (-65 min) and time spent in recovery activities increased on workdays (+53 min). The pattern of findings was similar in subgroups defined by gender, family status and job situation.
A worktime reduction of 25% for full-time workers resulted in decreased total workload and an increase of time spent in recovery activities, which is in line with the suggestion that worktime reduction may be beneficial for long-term health and stress.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
gender; recovery; total workload; worktime reduction
The primary objective was to evaluate 6-month outcomes for brief and extensive automated telephony interventions targeting problematic alcohol use, in comparison to an assessment-only control group. The secondary objective was to compare levels of problematic alcohol use (hazardous, harmful or probable dependence), gender and age among study participants from clinical psychiatric and addiction outpatient settings and from population-based telephone helpline users and Internet help-seeker samples.
The Alcohol Use Disorders Identification Test (AUDIT) was used for screening of problematic alcohol use and 6-month follow-up assessment. A total of 248 of help-seekers with at least hazardous use (AUDIT scores of ≥ 6/≥ 8 for women/men) were recruited from clinical and general population settings. Minor recruitment group differences were identified with respect to AUDIT scores and age at baseline. One hundred and sixty persons (64.5%) did not complete the follow-up assessment. The attrition group had a higher proportion of probable dependence (71% vs. 56%; p = 0.025), and higher scores on the total AUDIT, and its subscales for alcohol consumption and alcohol problems. At follow up, within-group problem levels had declined across all three groups, but there were no significant between-group differences. Trial registration ClinicalTrials.gov NCT01958359, Registered October 9, 2013. Retrospectively registered.
Addiction; Alcohol; Automated; Dependence; Hazardous; Help seekers; Intervention; Outpatient; Psychiatry; Randomized; Telephone
Neuroimaging has evolved into a widely used method to investigate the functional neuroanatomy, brain-behaviour relationships, and pathophysiology of brain disorders, yielding a literature of more than 30,000 papers. With such an explosion of data, it is increasingly difficult to sift through the literature and distinguish spurious from replicable findings. Furthermore, due to the large number of studies, it is challenging to keep track of the wealth of findings. A variety of meta-analytical methods (coordinate-based and image-based) have been developed to help summarise and integrate the vast amount of data arising from neuroimaging studies. However, the field lacks specific guidelines for the conduct of such meta-analyses. Based on our combined experience, we propose best-practice recommendations that researchers from multiple disciplines may find helpful. In addition, we provide specific guidelines and a checklist that will hopefully improve the transparency, traceability, replicability and reporting of meta-analytical results of neuroimaging data.
Guidelines; Meta-analysis; Neuroimaging; PET; Ten simple rules; fMRI
Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) are often comorbid and share similarities across some cognitive phenotypes, including certain aspects of attention. However, no functional magnetic resonance imaging studies have compared the underlying neural mechanisms contributing to these shared phenotypes.
Age- and IQ-matched boys (11-17 years old) with ASD (n = 20), boys with OCD (n = 20), and healthy control boys (n = 20) performed a parametrically modulated psychomotor vigilance functional magnetic resonance imaging task. Brain activation and performance were compared among adolescents with OCD, adolescents with ASD, and control adolescents.
Whereas boys with ASD and OCD were not impaired on task performance, there was a significant group by attention load interaction in several brain regions. With increasing attention load, left inferior frontal cortex/insula and left inferior parietal lobe/pre/post-central gyrus were progressively less activated in boys with OCD relative to the other two groups. In addition, boys with OCD showed progressively increased activation with increasing attention load in rostromedial prefrontal/anterior cingulate cortex relative to boys with ASD and control boys. Shared neurofunctional abnormalities between boys with ASD and boys with OCD included increased activation with increasing attention load in cerebellum and occipital regions, possibly reflecting increased default mode network activation.
This first functional magnetic resonance imaging study to compare boys with ASD and OCD showed shared abnormalities in posterior cerebellar-occipital brain regions. However, boys with OCD showed a disorder-specific pattern of reduced activation in left inferior frontal and temporo-parietal regions but increased activation of medial frontal regions, which may potentially be related to neurobiological mechanisms underlying cognitive and clinical phenotypes of OCD.
ASD; Adolescence; Attention; OCD; Vigilance; fMRI
Alcohol use and alcohol-related problems, including accidents, vandalism and violence, at sporting events are of increased concern in Sweden and other countries. The relationship between alcohol use and violence has been established and can be explained by the level of intoxication. Given the occurrence of alcohol use and alcohol-related problems at sporting events, research has assessed intoxication levels measured through biological sampling among spectators. This cross-sectional study aimed to assess the level of alcohol intoxication among spectators at football matches in the Swedish Premier Football League. Spectators were randomly selected and invited to participate in the study. Alcohol intoxication was measured with a breath analyser for Blood Alcohol Concentration levels, and data on gender, age, and recent alcohol use were gathered through a face-to-face interview. Blood Alcohol Concentration samples from 4420 spectators were collected. Almost half (46.8%) had a positive Blood Alcohol Concentration level, with a mean value of 0.063%, while 8.9% had a Blood Alcohol Concentration level ≥ 0.1%, with a mean value of 0.135%. Factors that predicted a higher Blood Alcohol Concentration level included male gender (p = 0.005), lower age (p < 0.001), attending a local derby (p < 0.001), alcohol use prior to having entered the arena (p < 0.001), attending a weekend match (p < 0.001), and being a spectator at supporter sections (p < 0.001). About half of all spectators at football matches in the Swedish Premier Football League drink alcohol in conjunction with the match. Approximately one tenth have a high level of alcohol intoxication.
The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.Molecular Psychiatry advance online publication, 14 November 2017; doi:10.1038/mp.2017.215.
Where one looks within their environment constrains one's visual experiences, directly affects cognitive, emotional, and social processing [1-4], influences learning opportunities , and ultimately shapes one's developmental path. While there is a high degree of similarity across individuals with regard to which features of a scene are fixated [6-8], large individual differences are also present, especially in disorders of development [9-13], and clarifying the origins of these differences is essential to understand the processes by which individuals develop within the complex environments in which they exist and interact. Toward this end, a recent paper  found that "social visual engagement"-namely, gaze to eyes and mouths of faces-is strongly influenced by genetic factors. However, whether genetic factors influence gaze to complex visual scenes more broadly, impacting how both social and non-social scene content are fixated, as well as general visual exploration strategies, has yet to be determined. Using a behavioral genetic approach and eye tracking data from a large sample of 11-year-old human twins (233 same-sex twin pairs; 51% monozygotic, 49% dizygotic), we demonstrate that genetic factors do indeed contribute strongly to eye movement patterns, influencing both one's general tendency for visual exploration of scene content, as well as the precise moment-to-moment spatiotemporal pattern of fixations during viewing of complex social and non-social scenes alike. This study adds to a now growing set of results that together illustrate how genetics may broadly influence the process by which individuals actively shape and create their own visual experiences.
autism; behavioral genetics; development; dynamic systems; evocative effects; eye gaze; eye tracking; gene environment correlation; neurodevelopmental disorders; selective attention
Environmental exposures to essential and toxic elements may alter health trajectories, depending on the timing, intensity, and mixture of exposures. In epidemiologic studies, these factors are typically analyzed as a function of elemental concentrations in biological matrices measured at one or more points in time. Such an approach, however, fails to account for the temporal cyclicity in the metabolism of environmental chemicals, which if perturbed may lead to adverse health outcomes. Here, we conceptualize and apply a non-linear method-recurrence quantification analysis (RQA)-to quantify cyclical components of prenatal and early postnatal exposure profiles for elements essential to normal development, including Zn, Mn, Mg, and Ca, and elements associated with deleterious health effects or narrow tolerance ranges, including Pb, As, and Cr. We found robust evidence of cyclical patterns in the metabolic profiles of nutrient elements, which we validated against randomized twin-surrogate time-series, and further found that nutrient dynamical properties differ from those of Cr, As, and Pb. Furthermore, we extended this approach to provide a novel method of quantifying dynamic interactions between two environmental exposures. To achieve this, we used cross-recurrence quantification analysis (CRQA), and found that elemental nutrient-nutrient interactions differed from those involving toxicants. These rhythmic regulatory interactions, which we characterize in two geographically distinct cohorts, have not previously been uncovered using traditional regression-based approaches, and may provide a critical unit of analysis for environmental and dietary exposures in epidemiological studies.
This study describes 1-year treatment outcomes from a large sample of cognitive-behavioral therapy (CBT) responders, investigates age as a possible moderator of these treatment outcomes, and evaluates clinical relapse at the 1-year follow-up.
This study is the planned follow-up to the Nordic Long-term OCD [obsessive-compulsive disorder] Treatment Study (NordLOTS), which included 177 children and adolescents who were rated as treatment responders following CBT for OCD. Participants were assessed with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) at 6- and 12-month follow-up. Treatment response and remission were defined as CY-BOCS total scores ≤15 and ≤10, respectively. Linear mixed-effects models were used to analyze all outcomes.
At 1 year, a total of 155 children and adolescents (87.6%) were available for follow-up assessment, with 142 of these (91.6%) rated below a total score of ≤15 on the CY-BOCS. At 1-year follow-up, 121 (78.1%) were in remission. On average, CY-BOCS total scores dropped by 1.72 points during the first year after terminating treatment (p = .001). A total of 28 participants (15.8%) relapsed (CY-BOCS ≥ 16) at either the 6- or 12-month assessment; only 2 patients required additional CBT.
Results suggest that manualized CBT in a community setting for pediatric OCD has durable effects for those who respond to an initial course of treatment; children and adolescents who respond to such treatment can be expected to maintain their treatment gains for at least 1 year following acute care. Clinical trial registration information- Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119.
Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
cognitive-behavioral therapy; follow-up; obsessive-compulsive disorder; pediatric; treatment
This paper is the first in a planned series of papers studying the effectiveness of psychotherapy and counselling in Nairobi. It describes a method for checking the effectiveness of psychotherapy and improving service quality in a Kenyan context. Rather than prematurely imposing psychotherapy protocols developed in Western countries in another cultural context, we believe that first studying psychological interventions as they are practised may generate understanding of which psychological problems are common, what interventions therapists use, and what seems to be effective in reducing psychiatric problems. The initial step is to assess outcome of psychological treatments as they are conducted. This is followed by statistical analyses aimed at identifying patient groups who are not improving at acceptable rates. Therapists will then be trained in a 'best practice' approach, and controlled trials are used in a final step, testing new interventions specifically targeted at patient groups with sub-optimal outcomes.
In published clinical and autobiographical accounts of eating disorders, patients often describe their disorder in personified ways, that is, relating to the disorder as if it were an entity, and treatment often involves techniques of externalization. By encouraging patients to think about their eating disorder as a relationship, this study aimed to examine how young female patients experience their eating disorder as acting towards them, how they react in response, and whether these interactions are associated with symptoms, illness duration, and self-image.
Structural Analysis of Social Behavior (SASB) was used to operationalize how patients experience the actions of their eating disorder and their own reactions to the disorder.
The relationship between patients (N = 150) and their eating disorders was examined with respect to symptoms, duration of illness, and self-image. Patients were also compared on their tendency to react with affiliation in relation to their disorder.
Patients' responses on the SASB indicated that they tended to conceptualize their eating disorders as blaming and controlling, and they themselves as sulking and submitting in response. Greater experience of the eating disorder as being controlling was associated with higher levels of symptomatology. Patients reacting with more negative affiliation towards their disorder were less symptomatic.
When encouraging patients to think about their eating disorder as a relationship, comprehensible relationship patterns between patients and their eating disorders emerged. The idea that this alleged relationship may resemble a real-life relationship could have theoretical implications, and its exploration may be of interest in treatment.
Patients were able to conceptualize their eating disorder as a significant other to whom they relate when encouraged to do so. Patients tended to experience their disorder as controlling and domineering. Exploring the hypothetical patient-eating disorder relationship may prove helpful in understanding dysfunctional relational patterns. Helping patients to rebel against their eating disorder could potentially aid in symptom reduction.
© 2017 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of British Psychological Society.
control; eating disorders; intrapersonal relationship; self-image; submission
Targeting of the human ribosome is an unprecedented therapeutic modality with a genome-wide selectivity challenge. A liver-targeted drug candidate is described that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small molecules. Key to the concept was the identification of pharmacologically active zwitterions designed to be retained in the liver. Oral delivery of the poorly permeable zwitterions was achieved by prodrugs susceptible to cleavage by carboxylesterase 1. The synthesis of select tetrazole prodrugs was crucial. A cell-free in vitro translation assay containing human cell lysate and purified target mRNA fused to a reporter was used to identify active zwitterions. In vivo PCSK9 lowering by oral dosing of the candidate prodrug and quantification of the drug fraction delivered to the liver utilizing an oral positron emission tomography 18 F-isotopologue validated our liver-targeting approach.
PCSK9; prodrugs; ribosome; tetrazoles; zwitterions
Positron emission tomography (PET), together with a suitable radioligand, is one of the more prominent methods for measuring changes in synaptic neurotransmitter concentrations in vivo. The radioligand of choice for such measurements on the cholinergic system is the muscarinic receptor antagonist N-[1-11C]propyl-3-piperidyl benzilate (PPB). In an effort to overcome the shortcomings with the technically cumbersome synthesis of [11C]PPB, we designed and synthesized four structurally related analogues of PPB, of which (S,R)-1-methylpiperidin-3-yl)2-cyclopentyl-2-hydroxy-2-phenylacetate (1) was found to bind muscarinic receptors with similar affinity as PPB (3.5 vs 7.9 nM, respectively). (S,R)-1 was radiolabeled via N-11C-methylation at high radiochemical purity (>99%) and high specific radioactivity (>130 GBq/μmol). In vitro studies by autoradiography on human brain tissue and in vivo studies by PET in nonhuman primates demonstrated excellent signal-to-noise ratios and a kinetic profile in brain comparable to that of [11C]PBB. (S,R)-[11C]1 is a promising candidate for measuring changes in endogenous acetylcholine concentrations.
PET; acetylcholine; carbon-11; muscarinic; radioligand; receptor
Allergy is associated with non-specific symptoms such as fatigue, sleep problems and impaired cognition. One explanation could be that the allergic inflammatory state includes activation of immune cells in the brain, but this hypothesis has not been tested in humans. The aim of the present study was therefore to investigate seasonal changes in the glial cell marker translocator protein (TSPO), and to relate this to peripheral inflammation, fatigue and sleep, in allergy. We examined 18 patients with severe seasonal allergy, and 13 healthy subjects in and out-of pollen season using positron emission tomography (n = 15/13) and the TSPO radioligand [11C]PBR28. In addition, TNF-α, IL-5, IL-6, IL-8 and IFN-γ were measured in peripheral blood, and subjective ratings of fatigue and sleepiness as well as objective and subjective sleep were investigated. No difference in levels of TSPO was seen between patients and healthy subjects, nor in relation to pollen season. However, allergic subjects displayed both increased fatigue, sleepiness and increased percentage of deep sleep, as well as increased levels of IL-5 and TNF-α during pollen season, compared to healthy subjects. Allergic subjects also had shorter total sleep time, regardless of season. In conclusion, allergic subjects are indicated to respond to allergen exposure during pollen season with a clear pattern of behavioral disruption and peripheral inflammatory activation, but not with changes in brain TSPO levels. This underscores a need for development and use of more specific markers to understand brain consequences of peripheral inflammation that will be applicable in human subjects.
Allergy; Cytokines; Fatigue; Immune-to-brain signaling; Positron emission tomography; Sickness behavior; Sleep
Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers.
Autism Spectrum Disorder; computational modeling; decision-making; fMRI; obsessive-compulsive disorder
To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations.
Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010-December 2014) period were prospectively included. Repeated-measures t-tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after.
After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P=0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P=0.00005). These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed. No pre-post differences were detected in the number of exacerbations not requiring admission.
Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA. Clinical trials with a larger number of patients are needed in order to confirm these results.
COPD; bronchiectasis; colistin; nebulized antibiotics
Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 × 10-11) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with symptoms including intrusive thoughts and time-consuming repetitive behaviors. Here Noh and colleagues identify genes enriched for functional variants associated with increased risk of OCD.
The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Mental disorders have become a major health issue, and a substantial number of afflicted individuals do not get appropriate treatment. Web-based interventions are promising supplementary tools for improving health care for patients with mental disorders, as they can be delivered at low costs and used independently of time and location. Although psychodynamic treatments are used frequently in the face-to-face setting, there has been a paucity of studies on psychodynamic Web-based self-help interventions.
The objective of this study was to determine the feasibility and preliminary efficacy of a transdiagnostic affect-focused psychodynamic Web-based self-help intervention designed to increase emotional competence of patients with mental disorders.
A total of 82 psychotherapy inpatients with mixed diagnoses were randomized into two groups. Following discharge, the intervention group (IG) got access to a guided version of the intervention for 10 weeks. After a waiting period of 10 weeks, the wait-list control group (WLCG) got access to an unguided version of the intervention. We reported the assessments at the beginning (T0) and at the end of the intervention, resp. the waiting period (T1). The primary outcome was satisfaction with the treatment at T1. Secondary outcome measures included emotional competence, depression, anxiety, and quality of life. Statistical analyses were performed with descriptive statistics (primary outcome) and analysis of covariance; a repeated measurement analysis of variance was used for the secondary outcomes. Effect sizes were calculated using Cohen d and data were analyzed as per protocol, as well as intention-to-treat (ITT).
Patients were chronically ill, diagnosed with multiple diagnoses, most frequently with depression (84%, 58/69), anxiety (68%, 47/69), personality disorder (38%, 26/69), and depersonalization-derealization disorder (22%, 15/69). A majority of the patients (86%, 36/42) logged into the program, of which 86% (31/36) completed the first unit. Satisfaction with the units mastered was rated as good (52%, 16/31) and very good (26%, 9/31). However, there was a steady decline of participation over the course of the program; only 36% of the participants (13/36) participated throughout the trial completing at least 50% of the sessions. According to the ITT analysis, participants improved statistically significantly and with moderate effect sizes (Cohen d) compared with the WLCG regarding depression (d=0.60), quality of life (d=0.53), and emotional competence (d=0.49). Effects were considerably stronger for the completers with respect to depression (d=1.33), quality of life (d=0.83), emotional competence (d=0.68), and general anxiety (d=0.62).
Although overall program satisfaction and benefit of the program were favorable with respect to the indicators of emotional disorders, the rate of completion was low. Our findings point to the need to target the intervention more specifically to the needs and capabilities of participants and to the context of the intervention.
©Rüdiger Zwerenz, Jan Becker, Robert Johansson, Ronald J Frederick, Gerhard Andersson, Manfred E Beutel. Originally published in JMIR Mental Health (http://mental.jmir.org), 16.10.2017.
Internet; aftercare; clinical trial; emotion-focused therapy; inpatients; psychoanalytic psychotherapy
Interest has increased in programs offering self-admission to inpatient treatment for patients with severe psychiatric illness, whereby patients who are well-known to a service are afforded the opportunity to admit themselves at will for a brief period of time. The aim of the present study was to examine patient experiences of practical considerations during the start-up phase of a self-admission program in an eating disorder service.
Sixteen adult participants in a self-admission program at a specialist eating disorders service were interviewed at 6 months about their experiences during the implementation phase. A qualitative content analysis approach was applied in order to identify recurring themes.
Six subcategories regarding implementation and logistics of self-admission were identified: "Start-up problems", "Problems associated with reserving a bed", "Lack of staff continuity", "Not enough emphasis on long-term goals", "Too demanding in terms of freedom and responsibility", and "Suggestions for alternative models".
Practical recommendations can be offered for the implementation of future self-admission programs, such as thoroughly informing all participants about the rationale behind self-admission with particular emphasis on patient accountability, establishing a waiting list procedure for occasions when all designated beds are occupied, and assigning an individual contact staff member responsible for each self-admitted patient.
The study protocol is retrospectively registered at ClinicalTrials.gov as ID: NCT02937259 .
Inpatients; Patient admissions; Patient participation; Psychiatry; Voluntary admissions
The Hypersexual Disorder Screening Inventory (HDSI) was developed by the American Psychiatric Association for clinical screening of hypersexual disorder (HD).
To examine the distribution of the proposed diagnostic entity HD according to the HDSI in a sample of men and women seeking help for problematic hypersexuality and evaluate some psychometric properties.
Data on sociodemographics, the HDSI, the Sexual Compulsivity Scale (SCS), and the Cognitive and Behavioral Outcomes of Sexual Behavior were collected online from 16 women and 64 men who self-identified as hypersexual. Respondents were recruited by advertisements offering psychological treatment for hypersexual behavior.
The HDSI, covering the proposed criteria for HD.
Of the entire sample, 50% fulfilled the criteria for HD. Compared with men, women scored higher on the HDSI, engaged more often in risky sexual behavior, and worried more about physical injuries and pain. Men primarily used pornography, whereas women had sexual encounters. The HD group reported a larger number of sexual specifiers, higher scores on the SCS, more negative effects of sexual behavior, and more concerns about consequences compared with the non-HD group. Sociodemographics had no influence on HD. The HDSI's core diagnostic criteria showed high internal reliability for men (α = 0.80) and women (α = 0.81). A moderate correlation between the HDSI and the SCS was found (0.51). The vast majority of the entire sample (76 of 80, 95%) fulfilled the criteria for sexual compulsivity according to the SCS.
The HDSI could be used as a screening tool for HD, although further explorations of the empirical implications regarding criteria are needed, as are refinements of cutoff scores and specific sexual behaviors. Hypersexual problematic behavior causes distress and impairment and, although not included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, HD should be endorsed as a diagnosis to develop evidence-based treatment and future studies on its etiology. Öberg KG, Hallberg J, Kaldo V, et al. Hypersexual Disorder According to the Hypersexual Disorder Screening Inventory in Help-Seeking Swedish Men and Women With Self-Identified Hypersexual Behavior. Sex Med 2017;5:e229-e236.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Gender; Hypersexual Disorder; Hypersexual Disorder Screening Inventory; Screening Inventory; Sexual Compulsivity
Psychopathy comprises interpersonal, affective, lifestyle and antisocial facets that vary dimensionally in the population and are associated with criminal offending and adverse psychosocial outcomes. Evidence associating these facets with white matter microstructure of the uncinate fasciculus and the cingulum tracts is inconsistent and derives principally from studies of male offenders. In a sample of 99 young women presenting a range of scores on the Psychopathy Checklist: Screening Version, we used Diffusion Tensor Imaging, tractography and Tract-Based Spatial Statistics to investigate microstructure across the brain and of the uncinate fasciculus and cingulum. Right uncinate fasciculus microstructure was negatively associated with the interpersonal facet, while cingulum integrity was not associated with any facet of psychopathy. Whole-brain analyses revealed that both affective and lifestyle facets were negatively correlated with white matter microstructure adjacent to the fusiform gyrus, and the interpersonal facet correlated negatively with the integrity of the fornix. Findings survived adjustment for the other facet scores, and age, verbal and performance IQ. A similar negative association between the interpersonal facet and uncinate fasciculus integrity was previously observed in male offenders. Thus, previous evidence showing that psychopathic traits are associated with functional and structural abnormalities within limbic networks may also apply to females.
TBSS; cingulum; fornix; fusiform gyrus; tractography; uncinate fasciculus
Electroconvulsive therapy (ECT) is effective in bipolar depression, but relapse is common. The aim of the study was (i) to identify prognostic factors (ii) and to determine the impact of pharmacological approaches on the risk for rehospitalization or suicide.
This register study analyzed data from individuals treated with inpatient ECT for bipolar depression. Subjects were identified using the Swedish National Patient Register between 2011 and 2014 and the Swedish National Quality Register for ECT. Other national registers provided data on psychopharmacotherapy, socio-demographic factors, and causes of death. The endpoint was the composite of rehospitalization for any psychiatric disorder, suicide attempt or completed suicide (RoS). Cox regression was used to calculate hazard ratios in univariate and multivariate models.
Data from 1255 patients were analyzed. The mean period of follow-up was 346 days. A total of 29%, 41%, and 52% of patients reached RoS at 3, 6, and 12 months post-discharge. A history of multiple psychiatric admissions, lower age, and post-discharge treatment with antipsychotics or benzodiazepines was associated with RoS.
Indication bias may have affected the results.
A history of multiple hospital admissions and lower age are key predictors of the composite of rehospitalization or suicide in patients treated with ECT for bipolar depression. Lithium might be effective. By contrast, antipsychotics and benzodiazepines were associated with increased risk, but possibly this finding was influenced by indication bias.
Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Depression can negatively impact work capacity, but treatment effects on sick leave and employment are unclear. This study evaluates if internet-based cognitive behavioural therapy (ICBT) or physical exercise (PE), with already reported positive effects on clinical outcome and short-term work ability, has better effects on employment, sick leave and long-term work ability compared with treatment as usual (TAU) for depressed primary care patients (German clinical trials: DRKS00008745).
After randomisation and exclusion of patients not relevant for work-related analysis, patients were divided into two subgroups: initially unemployed (total n=118) evaluated on employment, and employed (total n=703) evaluated on long-term sick leave. Secondary outcomes were self-rated work ability and average number of sick days per month evaluated for both subgroups. Assessments (self-reports) were made at baseline and follow-up at 3 and 12 months.
For the initially unemployed subgroup, 52.6% were employed after 1 year (response rate 82%). Both PE (risk ratio (RR)=0.44; 95% CI 0.23 to 0.87) and ICBT (RR=0.37; 95% CI 0.16 to 0.84) showed lower rates compared with TAU after 3 months, but no difference was found after 1 year (PE: RR=0.97; 95% CI 0.69 to 1.57; ICBT: RR=1.23; 95% CI 0.72 to 2.13). For those with initial employment, long-term sick leave (response rate 75%) decreased from 7.8% to 6.5%, but neither PE (RR=1.4; 95% CI 0.52 to 3.74) nor ICBT (RR=0.99; 95% CI 0.39 to 2.46) decreased more than TAU, although a temporary positive effect for PE was found. All groups increased self-rated work ability with no differences found.
No long-term effects were found for the initially unemployed on employment status or for the initially employed on sick leave. New types of interventions need to be explored.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
cognitive behavioral therapy; depression; internet therapy; physical exercise; return to work
Blood; Cognition; Cytokine; Schizophrenia
The serotonergic system is widely present in all regions of the central nervous system (CNS) and plays a key modulatory role in many of its functions. Positron emission tomography (PET) is used to study several serotonin receptors in CNS in vivo. The G-protein coupled receptor 5-HT1B is mostly present in the occipital cortex and in midbrain and is linked to several psychiatric disorders. There is evidence that agonist PET radioligands for neuroreceptors are more sensitive to endogenous neurotransmitters than antagonists. Our previously developed 5-HT1B receptor PET radioligand, [11C]AZ10419369, is now considered a partial agonist. In this work we are aiming to develop a full antagonist PET radioligand for imaging brain 5-HT1B receptors, and evaluate its sensitivity to increased endogenous serotonin concentration.
[11C]AZ10419096 was synthesized by rapid methylation of the prepared corresponding N-desmethyl precursor with [11C]methyl triflate. Five PET measurements were performed in cynomolgus monkeys, consisting of two at baseline, one after treatment of a monkey with a 5-HT1B antagonist, AR-A000002, and two in which fenfluramine was administered during scanning to induce endogenous serotonin release.
[11C]AZ10419096 was synthesized in high yield and purity within 30 min, including purification, formulation and sterile filtration. The baseline PET measurements demonstrated [11C]AZ10419096 to have favorable radioligand characteristics, including high specific binding in brain regions that have high 5-HT1B density, such as occipital cortex and globus pallidus, as well as subsequent rapid elimination from brain and a minor abundance of lipophilic radiometabolites in plasma. AR-A00002 completely blocked radioligand receptor-specific binding. Fenfluramine produced a distinct displacement of radioligand consistent with an expected increase of synaptic endogenous serotonin concentration.
[11C]AZ10419096, a full 5-HT1B antagonist PET radioligand, demonstrates high specific binding in monkey brain that is sensitive to competition from a known 5-HT1B antagonist as well as to putatively increased endogenous serotonin levels.
Published by Elsevier Inc.
5-HT(1B) receptor; Antagonist; Carbon-11; PET; Radioligand
Clinical supervision is a central part of psychotherapist training but the empirical support for specific supervision theories or features is unclear. The aims of this study were to systematically review the empirical research literature regarding the effects of clinical supervision on therapists' competences and clinical outcomes within Cognitive Behavior Therapy (CBT). A comprehensive database search resulted in 4103 identified publications. Of these, 133 were scrutinized and in the end 5 studies were included in the review for data synthesis. The five studies were heterogeneous in scope and quality and only one provided firm empirical support for the positive effects of clinical supervision on therapists' competence. The remaining four studies suffered from methodological weaknesses, but provided some preliminary support that clinical supervision may be beneficiary for novice therapists. No study could show benefits from supervision for patients. The research literature suggests that clinical supervision may have some potential effects on novice therapists' competence compared to no supervision but the effects on clinical outcomes are still unclear. While bug-in-the-eye live supervision may be more effective than standard delayed supervision, the effects of specific supervision models or features are also unclear. There is a continued need for high-quality empirical studies on the effects of clinical supervision in psychotherapy.
Clinical supervision; Cognitive Behavior Therapy; empirical research; review; training
Employing national registers for research purposes depends on a high diagnostic validity. The aim of the present study was to examine the diagnostic validity of recorded diagnoses of early-onset obsessive-compulsive disorder (OCD) in the Danish Psychiatric Central Register (DPCR).
Review of patient journals selected randomly through the DPCR.
One hundred cases of OCD were randomly selected from DPCR. Using a predefined coding scheme based on the Children's Yale Brown Obsessive Compulsive Scale (CYBOCS), experienced research nurse or child and adolescent psychiatrists assessed each journal to determine the presence/absence of OCD diagnostic criteria. The detailed assessments were reviewed by two senior child and adolescent psychiatrists to determine if diagnostic criteria were met.
Positive predictive value (PPV) was used as the primary outcome measurement.
A total of 3462 children/adolescents received an OCD diagnosis as the main diagnosis between 1 January 1995 and 31 December 2015. The average age at diagnosis was 13.21±2.89 years. The most frequent registered OCD subcode was the combined diagnosis DF42.2. Of the 100 cases we examined, 35 had at least one registered comorbidity. For OCD, the PPV was good (PPV 0.85). Excluding journals with insufficient information, the PPV was 0.96. For the subcode F42.2 the PPV was 0.77. The inter-rater reliability was 0.94. The presence of the CYBOCS in the journal significantly increased the PPV for the OCD diagnosis altogether and for the subcode DF42.2.
The validity and reliability of International Classification of Disease 10th revision codes for OCD in the DPCR is generally high. The subcodes for predominant obsessions/predominant compulsions are less certain and should be used with caution. The results apply for both children and adolescents and for both older and more recent cases. Altogether, the study suggests that there is a high validity of the OCD diagnosis in the Danish National Registers.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
OCD; Obsessive-Compulsive Disorder; early-onset; register study; validation study
Few studies have addressed the relationship between dementia and crime. We conducted a study of persons who got a primary or secondary diagnosis of dementia or cognitive disorder in a forensic psychiatric examination.
In Sweden, annually about 500 forensic psychiatric examinations are carried out. All cases from 2008 to 2010 with the diagnoses dementia or cognitive disorder were selected from the database of the Swedish National Board of Forensic Medicine. Out of 1471 cases, there were 54 cases of dementia or cognitive disorder. Case files were scrutinized and 17 cases of dementia and 4 cases of cognitive disorder likely to get a dementia diagnosis in a clinical setting were identified and further studied.
There were 18 men and 3 women; Median age 66 (n = 21; Range 35-77) years of age. Eleven men but no women had a previous criminal record. There were a total of 38 crimes, mostly violent, committed by the 21 persons. The crimes were of impulsive rather that pre-meditated character. According to the forensic psychiatric diagnoses, dementia was caused by cerebrovascular disorder (n = 4), alcohol or substance abuse (n = 3), cerebral haemorrhage and alcohol (n = 1), head trauma and alcohol (n = 2), Alzheimer's disease (n = 2), Parkinson's disease (n = 1), herpes encephalitis (n = 1) and unspecified (3). Out of four persons diagnosed with cognitive disorder, one also had delusional disorder and another one psychotic disorder and alcohol dependence. An alcohol-related diagnosis was established in ten cases. There were only two cases of Dementia of Alzheimer's type, one of whom also had alcohol intoxication. None was diagnosed with a personality disorder. All but one had a history of somatic or psychiatric comorbidity like head traumas, stroke, other cardio-vascular disorders, epilepsy, depression, psychotic disorders and suicide attempts. In this very ill group, the suggested verdict was probation in one case and different forms of care in the remaining 20 cases instead of prison.
Few cases of dementia or cognitive disorder were identified by forensic psychiatric examinations. All but one suffered from a variety of serious mental and medical conditions affecting the brain. Alcohol abuse was prevalent.
Co-morbidity-alcohol-elderly; Cognitive disorder; Dementia; Forensic psychiatric examination
Pediatric Acute Neuropsychiatric Syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are conditions marked by sudden onset of obsessive-compulsive disorder (OCD), tics, or avoidant/restrictive food intake in combination with multiple psychiatric symptoms. A diagnosis of PANS or PANDAS may be supported by the Cunningham Panel, a commercially available set of immunologic assays currently in clinical use. However, the relationship between Cunningham Panel results and patient symptoms remains unclear. This study was done to assess the diagnostic accuracy of the Cunningham Panel in patients with suspected PANS or PANDAS.
All Swedish patients who had taken the Cunningham Panel prior to June 2014 (n=154) were invited and 53 patients participated in the study. Based on comprehensive psychiatric assessment (the reference standard of diagnosis), subjects were classified as PANS, PANDAS, or neither. Prior Cunningham Panel test results were collected from patient records, and new blood samples were similarly analyzed within the scope of this study. In addition, results were compared to healthy controls (n=21) and a test-retest reliability analysis was performed.
Sensitivities of individual biomarkers in the Cunningham Panel ranged from 15 to 60%, and specificities from 28 to 92%. Positive predictive values ranged from 17 to 40%, and negative predictive values from 44 to 74%. A majority of the healthy controls had pathological Cunningham Panel results and test-retest reliability proved insufficient.
Clinical use of the Cunningham Panel in diagnosing PANS or PANDAS is not supported by this study.
Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Antibodies; Biomarkers; Calcium/calmodulin kinase II; Obsessive-compulsive disorder; PANDAS; PANS; Sensitivity and specificity
Family-based treatments are first-line treatments for adolescents with restrictive eating disorders (ED) but have to be improved since outcome is poor for some. We have investigated the one-year outcome of a family-based intervention programme with defined and decisive interventions at the start of treatment.
Data pertaining 201 adolescents with restrictive ED with features of anorexia nervosa but not fulfilling the weight criterion starting treatment 2010-2015, had a wide range of body mass index (BMI) and of weight loss at presentation, and completed a one-year follow-up was analysed. Recovery from the ED was defined as an Eating Disorder Examination-questionnaire (EDE-Q) score < 2.0 or as not fulfilling criteria for an ED at a clinical interview.
By EDE-Q 130 (65%) had recovered at 1 year and by clinical interview 106 (53%). According to the EDE-Q criterion recovery was independently associated with lower EDE-Q score at presentation, higher weight gain after 3 months of treatment and lower weight suppression at follow-up, weight suppression being defined as the difference between premorbid and current BMI. Not fulfilling criteria for an ED was associated with the same factors and also by higher BMI at presentation.
The observations that low weight and high ED cognitions confer a poor prognosis but that rapid weight gain at the start of treatment predicts a better prognosis are presently extended to adolescents with restrictive ED with a wide range of BMI at presentation. High weight suppression at follow-up is associated with a poor prognosis and indicates the importance of taking premorbid BMI into account when setting weight targets for treatment.
Adolescents; Anorexia nervosa; Early treatment response; Eating disorder; Family-based intervention; Weight suppression
Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre- and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.
Atypical gaze processing has been reported in children with autism spectrum disorders (ASD). Here we explored how infants at risk for ASD respond behaviorally to others' direct gaze. We assessed 10-month-olds with a sibling with ASD (high risk group; n = 61) and a control group (n = 18) during interaction with an adult. Eye-tracking revealed less looking at the adult in the high risk group during 300-1000 ms after the adult initiated direct gaze: a short alteration that is likely to go unnoticed by the naked eye. Data aggregated over longer segments (the traditional eye-tracking approach) showed no group differences. Although findings are limited by lack of outcome data, they are in line with theories linking atypical eye processing to the emergence of ASD.
Autism; Eye tracking; Neurodevelopmental disorders; Risk assessment; Sensorimotor development
Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting.
Depressed patients who underwent ECT in 2011-2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Åsberg Depression Rating Scale scores of 0-10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics.
Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus≥0.50ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission.
This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication.
Copyright © 2017 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.
ECT; Mania and bipolar disorder; Unipolar depression
The use of anabolic-androgenic steroids has increased among gym-goers, and it has been proposed that this may be part of a polysubstance use pattern that includes the use of illicit drugs. Still, epidemiological data on illicit drug use among gym-goers of both genders are meager. The aim of the present study was thus to examine the use of illicit drugs and its correlates in a large sample of men and women who engaged in weight training at gyms across Sweden.
In this cross-sectional study, a total of 1969 gym-goers who engaged in weight training in 54 gyms across Sweden were invited to fill in a questionnaire. The questionnaire included 25 items on background variables, weight training frequency, use of illicit drugs and doping substances, and non-medical use of benzodiazepines.
Of the gym-goers, 19.6% reported having ever used illicit drugs, 6.5% reported use during the past 12 months, and 2.1% during the past 30 days. The most commonly used drug was cannabis, followed by cocaine, amphetamine, and ecstasy. Almost 40% of those who reported drug use had used more than one drug. Male participants and participants between 20 and 39 years of age made up the majority of users. Furthermore, 5.1% of the reported drug users had ever used a doping substance. There was an almost threefold higher odds (OR = 2.99, 95% CI = 1.16-7.66, p < 0.023) of doping use among people who had reported drug use as compared to non-users.
Training at gyms is typically considered a health-promoting behavior. However, our results revealed a slightly higher prevalence of illicit drug use among gym attendees as compared to the general population. Our findings may have captured an underrecognized group of young adult males who engage in weightlifting and use illicit drugs recreationally and/or as training aids. Developing knowledge is imperative in orientating preventive efforts among at-risk gym-goers.
Anabolic-androgenic steroids; Cross-sectional study; Drug prevalence; Gym-goers; Illicit drug use
Being sensitive and responsive to others' internal states is critical for social life. One reliable cue to what others might be feeling is pupil dilation because it is linked to increases in arousal. When adults view an individual with dilated pupils, their pupils dilate in response, suggesting not only sensitivity to pupil size, but a corresponding response as well. However, little is known about the origins or mechanism underlying this phenomenon of pupillary contagion. Here we show that 4- to 6-month-old infants show pupillary contagion when viewing photographs of eyes with varying pupil sizes: their pupils dilate in response to others' large, but not small or medium pupils. The results suggest that pupillary contagion is likely driven by a transfer of arousal and that it is present very early in life in human infants, supporting the view that it could be an adaptation fundamental for social and emotional development.
Cognitive behavioral therapies have been shown to be effective for a variety of psychiatric and somatic disorders, but some obstacles can be noted in regular psychiatric care; for example, low adherence to treatment protocols may undermine effects. Treatments delivered via the Internet have shown promising results, and it is an open question if the blend of Internet-delivered and conventional face-to-face cognitive behavioral therapies may help to overcome some of the barriers of evidence-based treatments in psychiatric care.
We evaluated the feasibility of an Internet-based support system at an outpatient psychiatric clinic in Sweden. For instance, the support system made it possible to send messages and share information between the therapist and the patient before and after therapy sessions at the clinic.
Nine clinical psychologists participated and 33 patients were enrolled in the current study. We evaluated the usability and technology acceptance after 12 weeks of access. Moreover, clinical data on common psychiatric symptoms were assessed before and after the presentation of the support system.
In line with our previous study in a university setting, the Internet-based support system has the potential to be feasible also when delivered in a regular psychiatric setting. Notably, some components in the system were less frequently used. We also found that patients improved on common outcome measures for depressive and anxious symptoms (effect sizes, as determined by Cohen d, ranged from 0.20-0.69).
This study adds to the literature suggesting that modern information technology could be aligned with conventional face-to-face services.
©Kristoffer NT Månsson, Hugo Klintmalm, Ragnar Nordqvist, Gerhard Andersson. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 24.08.2017.
Internet-treatment; blended therapy; cognitive behavioral therapy; psychiatry
Chronic drug abuse leads to sex-specific changes in drug cue and stress physiologic and neuroendocrine reactivity as well as in neural responses to stress and cue-related challenges and in executive function such as inhibitory control, cognitive flexibility and self control. Importantly, these functions have been associated with high risk of relapse and treatment. Alpha-2 agonism may enhance inhibitory cognitive processes in the face of stress with sex-specific effects, however this has not been previously assessed in cocaine dependence.
Forty inpatient treatment-seeking cocaine dependent individuals (13F/27M) were randomly assigned to receive either placebo or up to 3mgs of Guanfacine. Three laboratory sessions were conducted following 3-4 weeks of abstinence, where patients were exposed to three 10-min personalized guided imagery conditions (stress, drug cue, combined stress/cue), one per day, on consecutive days in a random, counterbalanced order. The Stroop task was administered at baseline and immediately following imagery exposure.
Guanfacine treated women improved their performance on the Stroop task following exposure to all 3 imagery conditions compared with placebo women (p=0.02). This improvement in cognitive inhibitory performance was not observed in the men.
Enhancing the ability to cognitively regulate in the face of stress, drug cues and combined stress and drug cue reactivity may be key targets for medications development in cocaine dependent women.
Copyright © 2017 Elsevier B.V. All rights reserved.
Cocaine dependence; Cognitive inhibitory performance; Gender; Guanfacine; Stress
Reference tissue-based quantification of brain PET data does not typically include correction for signal originating from blood vessels, which is known to result in biased outcome measures. The bias extent depends on the amount of radioactivity in the blood vessels. In this study, we seek to revisit the well-established Logan plot and derive alternative formulations that provide estimation of distribution volume ratios (DVRs) that are corrected for the signal originating from the vasculature.
New expressions for the Logan plot based on arterial input function and reference tissue were derived, which included explicit terms for whole blood radioactivity. The new methods were evaluated using PET data acquired using [11C]raclopride and [18F]MNI-659. The two-tissue compartment model (2TCM), with which signal originating from blood can be explicitly modeled, was used as a gold standard. DVR values obtained for [11C]raclopride using the either blood-based or reference tissue-based Logan plot were systematically underestimated compared to 2TCM, and for [18F]MNI-659, a proportionality bias was observed, i.e., the bias varied across regions. The biases disappeared when optimal blood-signal correction was used for respective tracer, although for the case of [18F]MNI-659 a small but systematic overestimation of DVR was still observed.
The new method appears to remove the bias introduced due to absence of correction for blood volume in regular graphical analysis and can be considered in clinical studies. Further studies are however required to derive a generic mapping between plasma and whole-blood radioactivity levels.
Blood volume; Kinetic modeling; Logan plot; PDE10A; PET; [18F]MNI-659
Pain-related functional gastrointestinal disorders (P-FGIDs; eg, irritable bowel syndrome) are highly prevalent in children and associated with low quality of life, anxiety, and school absence. Treatment options are scarce, and there is a need for effective and accessible treatments. Internet-delivered cognitive behavior therapy (Internet-CBT) based on exposure exercises is effective for adult and adolescent irritable bowel syndrome, but it has not been evaluated for younger children.
The objective of this study was to assess acceptability, feasibility, and potential clinical efficacy of Internet-CBT for children with P-FGIDs.
This was a feasibility study with a within-group design. We included 31 children aged 8-12 years and diagnosed with P-FGID, according to the ROME III criteria. Mean duration of abdominal symptoms at baseline was 3.8 years (standard deviation [SD] 2.6). The treatment was therapist-guided and consisted of 10 weekly modules of exposure-based Internet-CBT. The children were instructed to provoke abdominal symptoms in a graded manner and to engage in previously avoided activities. The parents were taught to decrease their attention to their children's pain behaviors and to reinforce and support their work with the exposures. Assessments included treatment satisfaction, subjective treatment effect, gastrointestinal symptoms, quality of life, pain intensity, anxiety, depression, and school absence. Data were collected at pretreatment, posttreatment, and 6-month follow-up. Means, standard errors (SEs), and Cohen d effect sizes were estimated based on multi-level linear mixed models.
Most children 25/31 (81%) completed 9 or 10 of the 10 treatment modules. Almost all children, 28/31 (90%), reported that the treatment had helped them to deal more effectively with their symptoms, and 27/31 (87%) children declared that their symptoms had improved during the treatment. Assessments from the parents were in accordance with the children's reports. No child or parent reported that the symptoms had worsened. We observed a large within-group effect size on the primary outcome measure, child-rated gastrointestinal symptoms from pretreatment to posttreatment (Cohen d=1.14, P<.001, 95% CI 0.69-1.61), and this effect size was maintained at 6-month follow-up (Cohen d=1.40, P<.001, 95% CI 1.04-1.81). We also observed significant improvements from pretreatment to posttreatment on a wide range of child- and parent-rated measures including quality of life, pain intensity, anxiety, depression, and school absence. All results remained stable or were further improved at 6-month follow-up.
This study shows that children with longstanding P-FGIDs, and their parents, perceive exposure-based Internet-CBT as a helpful and feasible treatment. The included children improved significantly despite a long duration of abdominal symptoms before the intervention. The treatment shows potential to be highly effective for P-FGIDs. The results need to be confirmed in a randomized controlled trial (RCT).
©Maria Lalouni, Brjánn Ljótsson, Marianne Bonnert, Erik Hedman-Lagerlöf, Jens Högström, Eva Serlachius, Ola Olén. Originally published in JMIR Mental Health (http://mental.jmir.org), 10.08.2017.
abdominal pain; behavior therapy; cognitive therapy; functional gastrointestinal disorders; irritable bowel syndrome
The aim of the study was to objectively examine how sleep patterns were affected in a short- and long-term perspective after auricular acupuncture (AA) and cognitive behavioral therapy for insomnia (CBT-i). Sixty participants with insomnia disorders (men/women 9/51; mean age of 60.5 years, (SD 9.4)), were randomized to group treatment with AA or CBT-i. Actigraphy recordings were made at baseline, post-treatment and 6-month follow-up. The CBT-i group reduced their time in bed, their actual sleeping time, their sleep latency and their actual time awake. The AA group slept longer, increased their time in bed and decreased their sleep latency post-treatment. The between-groups results differed in wake-up time, rising, time in bed, actual sleep time and actual wake time. The differences were not maintained six months later. In accordance with previous findings the results support the notion that the objective sleep time does not necessarily affect the subjective perception of insomnia.
Actigraphy; Auricular acupuncture; Cognitive-behavioral therapy; Insomnia disorder; Non-pharmacological; Treatment
Autism spectrum disorder (ASD) has been found to be associated with alterations in resting state (RS) functional connectivity, including areas forming the default mode network (DMN) and salience network (SN). However, insufficient control for confounding genetic and environmental influences and other methodological issues limit the generalizability of previous findings. Moreover, it has been hypothesized that ASD might be marked by early hyper-connectivity followed by later hypo-connectivity. To date, only a few studies have explicitly tested age-related influences on RS connectivity alterations in ASD. Using a within-twin pair design (N=150 twins; 8-23 years), we examined altered RS connectivity between core regions of the DMN and SN in relation to autistic trait severity and age in a sample of monozygotic (MZ) and dizygotic (DZ) twins showing typical development, ASD or other neurodevelopmental conditions. Connectivity between core regions of the SN was stronger in twins with higher autistic traits compared to their co-twins. This effect was significant both in the total sample and in MZ twins alone, highlighting the effect of non-shared environmental factors on the link between SN-connectivity and autistic traits. While this link was strongest in children, we did not identify differences between age groups for the SN. In contrast, connectivity between core hubs of the DMN was negatively correlated with autistic traits in adolescents and showed a similar trend in adults but not in children. The results support hypotheses of age-dependent altered RS connectivity in ASD, making altered SN and DMN connectivity promising candidate biomarkers for ASD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.160.
There are no consistent predictors of treatment outcome in paediatric obsessive-compulsive disorder (OCD). One reason for this might be the use of suboptimal statistical methodology. Machine learning is an approach to efficiently analyse complex data. Machine learning has been widely used within other fields, but has rarely been tested in the prediction of paediatric mental health treatment outcomes.
To test four different machine learning methods in the prediction of treatment response in a sample of paediatric OCD patients who had received Internet-delivered cognitive behaviour therapy (ICBT).
Participants were 61 adolescents (12-17 years) who enrolled in a randomized controlled trial and received ICBT. All clinical baseline variables were used to predict strictly defined treatment response status three months after ICBT. Four machine learning algorithms were implemented. For comparison, we also employed a traditional logistic regression approach.
Multivariate logistic regression could not detect any significant predictors. In contrast, all four machine learning algorithms performed well in the prediction of treatment response, with 75 to 83% accuracy.
The results suggest that machine learning algorithms can successfully be applied to predict paediatric OCD treatment outcome. Validation studies and studies in other disorders are warranted.
Copyright © 2017 John Wiley & Sons, Ltd.
cognitive behaviour therapy; internet; machine-learning; obsessive-compulsive disorder; prediction
A significant number of Swedish practitioners are offered workshop trainings in motivational interviewing through community-based implementation programs. The objective of this randomized controlled trial was to evaluate to what extent the practitioners acquire and retain skills from additional supervision consisting of feedback based on monitoring of practice.
A total of 174 practitioners in five county councils across Sweden were randomized to one of the study's two groups: 1) Regular county council workshop training, 2) Regular county council workshop training followed by six sessions of supervision. The participant's mean age was 43.3 years, and the majority were females (88.1%).
Recruiting participants proved difficult, which may have led to a biased sample of practitioners highly motivated to learn the method. Although slightly different in form and content, all the workshop trainings increased the participants' skills to the same level. Also, consistent with previous research, the additional supervision group showed larger gains in proficiency compared to the group who received workshop training only at the six-month follow-up. However, analyses showed generally maintained levels of skills for all the participants at the follow-up assessment, and the majority of participants did not attain beginning proficiency levels at either post-workshop or follow-up.
The results of this study address the real-life implications of dissemination of evidence-based practices. The maintained level of elevated skills for all participants is a promising finding. However, the low interest for obtaining additional supervision among the Swedish practitioners is problematic. In addition, neither the workshop trainings nor the additional supervision, although improving skills, were sufficient for most of the participants to reach beginning proficiency levels. This raises questions regarding the most efficient form of training to attain and sustain adequate practice standards, and how to create incentive and interest among practitioners to participate in such training.
Kinetic modelling with metabolite-corrected arterial plasma is considered the gold standard for quantification of [11C]PBR28 binding to the translocator protein (TSPO), since there is no brain region devoid of TSPO that can serve as reference. The high variability in binding observed using this method has motivated the use of simplified ratio-based approaches such as standardised uptake value ratios (SUVRs) and distribution volume (VT) ratios (DVRs); however, the reliability of these measures and their relationship to VT have not been sufficiently evaluated.
Data from a previously published [11C]PBR28 test-retest study in 12 healthy subjects were reanalysed. VT was estimated using a two-tissue compartment model. SUVR and DVR values for the frontal cortex were calculated using the whole brain and cerebellum as denominators. Test-retest reliability was assessed for all measures. Interregional correlations were performed for SUV and VT, and principal component analysis (PCA) was applied. Lastly, correlations between ratio-based outcomes and VT were assessed.
Reliability was high for VT, moderate to high for SUV and SUVR, and poor for DVR. Very high interregional correlations were observed for both VT and SUV (all R 2 > 85%). The PCA showed that almost all variance (>98%) was explained by a single component. Ratio-based methods correlated poorly with VT (all R 2 < 34%, divided by genotype).
The reliability was good for SUVR, but poor for DVR. Both outcomes showed little to no association with VT, questioning their validity. The high interregional correlations for VT and SUV suggest that after dividing by a denominator region, most of the biologically relevant signal is lost. These observations imply that results from TSPO PET studies using SUVR or DVR estimates should be interpreted with caution.
DVR; PET; SUVR; TSPO; [11C]PBR28
Body dysmorphic disorder (BDD) is a relatively common and disabling psychiatric disorder characterised by excessive and persistent preoccupation with perceived defects or flaws in one's appearance, which are unnoticeable to others, and associated repetitive behaviours (eg, mirror checking). The disorder generally starts in adolescence, but often goes unnoticed and is severely underdiagnosed. Left untreated, BDD typically persists and causes marked functional impairment in multiple domains. This clinical review considers recent advances in the epidemiology and classification of BDD, including its reclassification in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders under the new 'Obsessive-Compulsive and Related Disorders' chapter. Key issues in assessment are outlined including the use of validated screening instruments to minimise misdiagnosis and the importance of risk assessment in this population given the high rates of suicidality and inappropriate use of cosmetic treatments. In addition, current knowledge regarding the causes and mechanisms underlying BDD are summarised. The recommended treatments for BDD are outlined, namely cognitive behavioural therapy (CBT) and antidepressants, such as selective serotonin reuptake inhibitors. Both CBT and pharmacotherapy have been shown to be efficacious treatments for BDD in adult populations, and evidence is emerging to support their use in young people. Although the majority of patients improve with existing evidence-based treatment, a large proportion are left with clinically significant residual symptoms. Priorities for future research are therefore discussed including the need to further refine and evaluate existing interventions with the goal of improving treatment outcomes and to increase their availability.
antidepressants; body dysmorphic disorder; cognitive behavioural therapy; diagnosis; treatment
Instruments have been developed to facilitate suicide risk assessment. We aimed to evaluate the evidence for these instruments including assessment of risk of bias and diagnostic accuracy for suicide and suicide attempt.
PubMed (NLM), PsycInfo, Embase, Cinahl and the Cochrane Library databases were searched until December 2014. We assessed risk of bias with QUADAS-2. The average sensitivity and specificity of each instrument was estimated and the certainty of the evidence was assessed with GRADE. We considered instruments with a sensitivity > 80% and a specificity > 50% to have sufficient diagnostic accuracy.
Thirty-five relevant studies were identified but 14 were considered to have high risk of bias, leaving 21 studies evaluating altogether 15 risk assessment instruments. We could carry out meta-analyses for five instruments. For the outcome suicide attempt SAD PERSONS Scale had a sensitivity of 15% (95% CI 8-24) and specificity of 97% (96-98), and the Manchester Self-Harm Rule (MSHR) a sensitivity of 97% (97-97) and a specificity of 20% (20-21). ReACT, which is a modification of MSHR, had a similar low specificity, as did the Sodersjukhuset Self Harm Rule. For the outcome suicide, the Beck Hopelessness Scale had a sensitivity of 89% (78-95) and specificity of 42% (40-43).
Most suicide risk assessment instruments were supported by too few studies to allow for evaluation of accuracy. Among those that could be evaluated, none fulfilled requirements for sufficient diagnostic accuracy.
The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.
While behavioural difficulties in facial emotion recognition (FER) have been observed in individuals with Autism Spectrum Disorder (ASD), behavioural studies alone are not suited to elucidate the specific nature of FER challenges in ASD. Eye tracking (ET) and electroencephalography (EEG) provide insights in to the attentional and neurological correlates of performance, and may therefore provide insight in to the mechanisms underpinning FER in ASD. Given that these processes develop over the course of the developmental trajectory, there is a need to synthesise findings in regard to the developmental stages to determine how the maturation of these systems may impact FER in ASD. We conducted a systematic review of fifty-four studies investigating ET or EEG meeting inclusion criteria. Findings indicate divergence of visual processing pathways in individuals with ASD. Altered function of the social brain in ASD impacts the processing of facial emotion across the developmental trajectory, resulting in observable differences in ET and EEG outcomes.
Affect; Asperger syndrome; Autism; EEG; Electrophysiology; Emotion recognition; Eye tracking
Craving is a clinically important feature of alcohol use disorders (AUD), representing a diagnostic criterion as well as a target for treatment. The Desire for Alcohol Questionnaire (DAQ) is a widely used scale to measure craving. The aim of the current study was to evaluate the psychometric properties of a Swedish version of the Shortened-DAQ.
The English DAQ was translated into Swedish and back translated to English. Individuals with a diagnosis of AUD (n=118) participated in a laboratory experiment comprising presentation of alcohol and non-alcohol cues, as well as consumption of an alcoholic drink, with the aim of exploring changes in the craving responses following pharmacological treatment for AUD. Subjective craving across the experimental conditions was recorded using Shortened-DAQ and a Visual Analogue Scale (VAS). The psychometric analysis of the Shortened-DAQ investigated some important aspects of reliability, validity and the factor solution using principal components analysis.
Cronbach's alphas were above 0.8 across all sessions, the test-retest correlations were statistically significant. In the alcohol cue session the Shortened-DAQ total score was significantly greater compared to the non-alcohol cue session, and correlated significantly with the VAS craving item across all sessions. The principal component analysis resulted in two significant factors comprised of (1) Alcohol desire and reinforcement and (2) Ability to control drinking. No difference in psychometric properties between treatment and placebo groups were found.
In future clinical studies on alcohol craving responses in Swedish patients with AUD, we suggest the use of the Swedish Shortened-DAQ, due to its comparably swift administration and overall acceptable psychometric properties.
Copyright © 2017 Elsevier Inc. All rights reserved.
Alcohol craving; Cue-induced craving; Desires for Alcohol Questionnaire; Psychometric evaluation
Twin studies of hoarding symptoms indicate low to moderate heritability during adolescence and considerably higher heritability in older samples, suggesting dynamic developmental etiological effects. The aim of the current study was to estimate the relative contribution of additive genetic and environmental effects to hoarding symptoms during adolescence and young adulthood and to estimate the sources of stability and change of hoarding symptoms during adolescence.
Univariate model-fitting was conducted in three cohorts of twins aged 15 (n = 7,905), 18 (n = 2,495) and 20-28 (n = 6,218). Longitudinal analyses were conducted in a subsample of twins for which data on hoarding symptoms was available at both age 15 and 18 (n = 1,701).
Heritability estimates for hoarding symptoms at ages 15, 18 and 20-28 were 41% (95% confidence interval [CI]: 36-45%), 31% (95% CI: 22-39%) and 29% (95% CI: 24-34%) respectively. Quantitative sex-differences emerged in twins aged 15 at which point the heritability in boys was 33% (95% CI: 22-41%) and 17% (95% CI: 0-36%) in girls. Shared environmental effects played a negligible role across all samples with the exception of girls aged 15 where they accounted for a significant proportion of the variance (22%; 95% CI 6-36%). The longitudinal bivariate analyses revealed a significant phenotypic correlation of hoarding symptoms between ages 15 and 18 (0.40; 95% CI: 0.36-0.44) and a strong but imperfect genetic correlation (0.75; 95% CI: 0.57-0.94). The bivariate heritability was estimated to 65% (95% CI: 50-79%).
Hoarding symptoms are heritable from adolescence throughout young adulthood, although heritability appears to slightly decrease over time. Shared environmental effects contribute to hoarding symptoms only in girls at age 15. The stability of hoarding symptoms between ages 15 and 18 is largely explained by genetic factors, while non-shared environmental factors primarily have a time-specific effect. The findings indicate that dynamic developmental etiological effects may be operating across the life span.
This 3-year follow-up compared insomnia treatment to depression treatment for patients with both diagnoses. Forty-three participants were randomized to either treatment, in the form of Internet-delivered therapist-guided cognitive behavior therapy (CBT), and 37 (86%) participants provided primary outcome data at the 3-year follow-up. After 3 years, reductions on depression severity were similar in both groups (between-group effect size, d = 0.33, p = .45), while the insomnia treatment had superior effects on insomnia severity (d = 0.66, p < .05). Overall, insomnia treatment was thus more beneficial than depression treatment. The implication for practitioners, supported by previous research, is that patients with co-occurring depression and insomnia should be offered CBT for insomnia, in addition to medication or psychological treatment for depression.
Cognitive behavioral therapy; Depression; Insomnia; Insomnia–comorbid; Long-term follow-up
Social skills group training (SSGT) for children and adolescents with autism spectrum disorder (ASD) is widely applied, but effectiveness in real-world practice has not yet been properly evaluated. This study sought to bridge this gap.
This 12-week pragmatic randomized controlled trial of SSGT compared to standard care alone was conducted at 13 child and adolescent psychiatry outpatient units in Sweden. Twelve sessions of manualized SSGT ("KONTAKT") were delivered by regular clinical staff. Participants (N = 296; 88 females and 208 males) were children (n = 172) and adolescents (n = 124) aged 8 to 17 years with ASD without intellectual disability. The primary outcome was the Social Responsiveness Scale rating by parents and blinded teachers. Secondary outcomes included parent- and teacher-rated adaptive behaviors, trainer-rated global functioning and clinical severity, and self-reported child and caregiver stress. Assessments were made at baseline, posttreatment, and 3-month follow-up. Moderator analyses were conducted for age and gender.
Significant treatment effects on the primary outcome were limited to parent ratings for the adolescent subgroup (posttreatment: -8.3; 95% CI = -14.2 to -1.9; p = .012, effect size [ES] = 0.32; follow-up: -8.6; 95% CI = -15.4 to -1.8; p = .015, ES = 0.33) and females (posttreatment: -8.9; 95% CI = -16.2 to -1.6; p = .019, ES = 0.40). Secondary outcomes indicated moderate effects on adaptive functioning and clinical severity.
SSGT for children and adolescents with ASD in regular mental health services is feasible and safe. However, the modest and inconsistent effects underscore the importance of continued efforts to improve SSGT beyond current standards.
Social Skills Group Training ("KONTAKT") for Children and Adolescent With High-functioning Autism Spectrum Disorders; https://clinicaltrials.gov/; NCT01854346.
Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
adolescence; autism spectrum disorder; gender; intervention; treatment
To examine the feasibility, efficacy, and effectiveness of PEGASUS, a group-based structured psychoeducation for adults with ADHD and their significant others.
A pragmatic parallel group add-on design multicenter randomized controlled trial was conducted, comparing an 8-session treatment with PEGASUS (allocated n=97; 48 with ADHD and 49 with significant others) to treatment as usual (TAU, allocated n=82; 39 with ADHD and 43 significant others). Participants (individuals with ADHD and significant others) were recruited from five psychiatric outpatient departments and block randomized to PEGASUS or TAU. Knowledge about ADHD was measured using the ADHD 20 scale pre- and post-intervention and served as primary outcome.
Knowledge about ADHD (d=0.97 [95% CI: 0.61-1.31]) increased following PEGASUS participation compared to TAU. Improvements were also observed in secondary outcomes e.g. global life satisfaction (d=0.25 [95% CI: from -0.09 to 0.59]). Overall treatment satisfaction was good. Over 90% of the participants completed the program. Post-intervention data was obtained from n=89 in PEGASUS group and n=70 in TAU group and analyses were conducted per protocol. No important adverse effects or side effects were observed.
Group-based structured psychoeducation PEGASUS for adults with ADHD and their significant others is a feasible, efficacious, and effective treatment option to increase ADHD knowledge and general life satisfaction in psychiatric outpatient care.
Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Attention deficit disorder with hyperactivity; Attitudes; Awareness; Health knowledge; Pedagogies; Practice; Randomized clinical trial (RCT)
[11C]-L-deprenyl-D2 is a positron emission tomography (PET) radioligand for measurement of the monoamine oxidase B (MAO-B) activity in vivo brain. The estimation of the test-retest reproducibility is important for accurate interpretation of PET studies.
We performed two [11C]-L-deprenyl-D2 scans for six healthy subjects and evaluated the test-retest variability of this radioligand. MAO-B binding was quantified by two tissue compartment model (2TCM) with three rate constants (K 1, k 2, k 3) using metabolite-corrected plasma radioactivity. The λk 3defined as (K 1/k 2) × k 3 was also calculated. The correlation between MAO-B binding and age, and the effect of partial volume effect correction (PVEc) for the reproducibility were also estimated. %difference of k 3 was 2.6% (medial frontal cortex) to 10.3% (hippocampus), and that of λk 3 was 5.0% (thalamus) to 9.2% (cerebellum). Mean %difference of all regions were 5.3 and 7.0% in k 3 and λk 3, respectively. All regions showed below 10% variabilities except the hippocampus in k 3 (10.3%). Intraclass correlation coefficient (ICC) of k 3 was 0.78 (hippocampus) to 0.98 (medial frontal cortex), and that of λk 3 was 0.78 (hippocampus) to 0.95 (thalamus). Mean ICC were 0.94 and 0.89 in k 3 and λk 3, respectively. The highest positive correlation with age was observed in the hippocampus, as r = 0.75 in k 3 and 0.76 in λk 3. After PVEc, mean %difference were 5.6 and 7.2% in k 3 and λk 3, respectively. Mean ICC were 0.92 and 0.90 for k 3 and λk 3, respectively. These values were almost the same as those before PVEc.
The present results indicate that k 3 and λk 3 of [11C]-L-deprenyl-D2 are reliable parameters for test-retest reproducibility with healthy subjects both before and after PVEc. The studies with patients of larger sample size are required for further clinical applications.
Age effect; Monoamine oxidase B; Partial volume effect correction; Positron emission tomography; Test-retest variability; [11C]-L-deprenyl-D2
Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group.
To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence DESIGN: Randomised controlled trial.
Online and telephone.
Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder.
42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care.
The primary outcome was depressive symptoms measured with the Montgomery-Åsberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed.
The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g =1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression.
Small sample size and no long-term evaluation.
Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.
Copyright © 2017. Published by Elsevier B.V.
Antenatal depression; Cognitive behavior therapy; Depression; Internet; Online; Perinatal mental health; Pregnancy; Psychotherapy; ehealth
We aimed to assess the extent to which adherence to, and recreational use of, psychotropic medications influence the risk of homicide offending and victimization.
We conducted a population-based case-control study by way of linking a nationwide registry of dispensed prescriptions with a forensic-toxicological database. Homicide victims (n = 200) and offenders (n = 105) were identified for the years 2007-2009 and vehicle-accident controls (n = 1,643) for the years 2006-2013. The occurrence of congruence and incongruence between dispensed prescriptions and toxicology was used as a measure of adherence and recreational use.
For antidepressants, incongruence-but not congruence-between dispensed prescriptions and toxicology was associated with a significantly increased risk of homicide offending (odds ratio adjusted for age and sex [aOR] = 6.2; 95% confidence interval [CI], 3.3-11.6) but not homicide victimization (aOR = 0.8; 95% CI, 0.3-2.0). For antipsychotics and mood stabilizers, a significantly increased risk of homicide offending was associated with incongruence between prescriptions and toxicology (aOR = 7.0; 95% CI, 2.8-17.7), whereas risk estimates for congruence were not significantly elevated for either homicide offending or victimization. For GABAergic hypnotics, congruence and incongruence were significantly associated with increased risks of both homicide offending (aOR = 5.4; 95% CI, 2.6-11.0 and aOR = 4.9; 95% CI, 2.6-9.3, respectively) and homicide victimization (aOR = 2.1; 95% CI, 1.1-4.2 and aOR = 3.2; 95% CI, 1.7-6.1, respectively). Sensitivity analyses with a subset of controls yielded similar estimates.
Nonadherence to medications used to treat affective and psychotic disorders appears to elevate the risk of homicide offending. Both medicinal and recreational use of GABAergic hypnotics appears to elevate the risk of homicide offending and victimization. In summary, vigilance regarding adherence to medications prescribed for mood disorders and psychosis, as well as restrictiveness regarding licit and illicit access to addictive hypnotics, might contribute to a reduction of homicidal violence.
© Copyright 2017 Physicians Postgraduate Press, Inc.
The proposed criteria of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition for hypersexual disorder (HD) included symptoms reported by patients seeking help for excessive and out-of-control non-paraphilic sexual behavior, including sexual behaviors in response to dysphoric mood states, impulsivity, and risk taking. Although no prior studies of cognitive-behavioral therapy (CBT) for the treatment of HD have been performed, CBT has been found effective for dysphoric mood states and impulsivity.
To investigate the feasibility of a CBT manual developed for HD explored through symptom decrease, treatment attendance, and clients' treatment satisfaction.
Ten men with a diagnosis of HD took part in the CBT group program. Measurements were taken before, during, and at the end of treatment and 3 and 6 months after treatment.
The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD:CAS) score that measured the severity of problematic hypersexual symptoms and secondary outcomes were the Hypersexual Disorder Screening Inventory (HDSI) score, the proportion of attended sessions, and the Client Satisfaction Questionnaire (CSQ-8) score.
Main results were significant decreases of HD symptoms from before to after treatment on HD:CAS and HDSI scores and a decrease in the number of problematic sexual behaviors during the course of therapy. A high attendance rate of 93% and a high treatment satisfaction score on CSQ-8 also were found.
The CBT program seemed to ameliorate the symptoms of HD and therefore might be a feasible treatment option.
This study provides data from a CBT program for the treatment of the specific proposed criteria of HD. Because of the small sample and lack of a control group, the results can be considered only preliminary.
Although participants reported decreased HD symptoms after attending the CBT program, future studies should evaluate the treatment program with a larger sample and a randomized controlled procedure to ensure treatment effectiveness. Hallberg J, Kaldo V, Arver S, et al. A Cognitive-Behavioral Therapy Group Intervention for Hypersexual Disorder: A Feasibility Study. J Sex Med 2017;14:950-958.
Copyright © 2017. Published by Elsevier Inc.
Client Satisfaction Questionnaire; Cognitive-Behavioral Therapy; Hypersexual Disorder; Hypersexual Disorder Screening Inventory; Hypersexual Disorder: Current Assessment Scale; Sexual Addiction; Treatment Satisfaction
Conclusions regarding lithium's antisuicidal effect for bipolar disorder have been limited due to nonrepresentative subjects and potential confounding factors, including varying severity of illness. Findings regarding the effect of valproate, the most common alternative to lithium, are inconsistent for suicidal behavior. This study investigated the associations of these two drugs with the risk of suicide-related events, and possible differences between drugs, by using within-individual designs in a register-based longitudinal cohort.
Through linkage of multiple Swedish national registers, 51,535 individuals with bipolar disorder were followed from 2005 to 2013 for treatment with lithium and valproate. Stratified Cox regression was used to estimate the hazard ratios of suicide-related events during treated periods compared with untreated periods. For significant associations between medication and suicide-related events, the population attributable fraction was estimated to assess the public health impact for patients with bipolar disorder.
During follow-up, 10,648 suicide-related events occurred. The incidence rate was significantly decreased by 14% during lithium treatment (hazard ratio 0.86, 95% confidence interval [CI] 0.78-0.95) but not during valproate treatment (hazard ratio 1.02, 95% CI 0.89-1.15). The difference in hazard ratios of suicide-related events between lithium and valproate was statistically significant. Estimates of the population attributable fraction suggested that 12% (95% CI 4%-20%) of suicide-related events could have been avoided if patients had taken lithium during the entire follow-up.
The results suggest that lithium should be considered for patients with bipolar disorder with suspected suicidal intentions, although risk for suicide is only one of the considerations when providing clinical care.
Anticonvulsants; Epidemiology; Lithium; Mood Disorders-Bipolar; Suicide
Eating disorders (ED) are prevalent, serious illnesses with elevated mortality, mainly attributable to suicide. Predictors of suicidality include binge/purge symptomatology, impulsivity, and psychiatric comorbidity, as well as personality factors. Recent research has also shown self-image (the Structural Analysis of Social Behavior, SASB, model) to predict manifest suicide attempts in ED, and the study explored suicide risk prediction to increase knowledge of warning signs and intervention targets.
Participants were adult ED patients registered in the Stepwise clinical database (N = 1537) with anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), or other specified feeding and eating disorder (OSFED). The SASB self-image questionnaire was used in stepwise regressions to predict 12-month suicidal ideation, both self- and clinician-rated, in models both excluding and including baseline clinical variables.
Validation analyses showed fair correspondence between outcome variables as well as with suicide attempts. Different variables predicted suicidality in different diagnoses, over and above baseline clinical variables in all but one regression model. Low Self-protection was important in AN and BN, high Self-control in AN, and high Letting go of the self in BN. For BED, self-blame explained variance, and in OSFED, lack of self-love.
Findings are in line with research showing differential self-image-based prediction of important outcomes in ED, with noteworthy consistencies across diagnoses and suicidality variables. Strengths included the large sample, and limitations pertained to measures, attrition and Type II error risk. Replication is needed, but findings are consistent with some previous work and offers clinical and research implications.
© 2017 Wiley Periodicals, Inc.
Although the Eating Disorder Examination Questionnaire (EDE-Q) is perhaps the single most widely used self-report measure of eating disorder (ED) symptoms, important questions remain about its validity and applicability in relation to particular groups of individuals, especially adolescents of both genders.
The present study investigated the factor structure of the adolescent version of the Eating Disorder Examination Questionnaire (EDE-Q) in samples of Swedish girls and boys from the general population and girls with a diagnosed eating disorder. Girls (N = 239) and boys (N = 248) aged between 13 and 15 years who were attending school, and girls (N = 570) aged between 12 and 14 years who were in treatment for an eating disorder at a specialist eating disorder clinic were assessed on the adolescent version of the EDE-Q.
The adolescent version of the EDE-Q demonstrated satisfactory levels of internal consistency. However, confirmatory factor analysis (CFA) failed to support the four-factor model of the EDE-Q. Parallel analysis (PA) and subsequent exploratory factor analysis (EFA) suggested that the adolescent version of the EDE-Q comprises one underlying factor in young adolescent girls (both clinical and general population), centred on Dissatisfaction with Shape and Weight. In boys three factors were found: Weight-related Concerns, Body Discomfort and Restraint.
The EDE-Q appears to measure different underlying aspects of eating disorder psychopathology in young teenagers compared to adults. The dimensions underlying disordered eating in young girls may become increasingly differentiated with time. There appear to be important gender-based differences in the dimensions underlying the EDE-Q in young teenagers. Therapists should be alert to beliefs that girls have about the importance of shape and weight, while in boys it may be more important to be attentive to how they feel about their bodies in relation to weight.
Adolescent; Assessment; Eating Disorder Examination Questionnaire; Eating disorders; Factor analysis; Measurement
Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
Cross-sectional studies have indicated impaired neurodevelopment with elevated drinking water manganese concentrations (W-Mn), but potential susceptible exposure windows are unknown.
We prospectively evaluated the effects of W-Mn, from fetal life to school age, on children's cognitive abilities and behavior.
We assessed cognitive abilities and behavior in 1,265 ten-year-old children in rural Bangladesh using the Wechsler Intelligence Scale for Children (WISC-IV) and the Strengths and Difficulties Questionnaire (SDQ), respectively. Manganese in drinking water used during pregnancy and by the children at 5 y and 10 y was measured using inductively coupled plasma mass spectrometry.
The median W-Mn was 0.20 mg/L (range 0.001–6.6) during pregnancy and 0.34mg/L (<0.001–8.7) at 10 y. In multivariable-adjusted linear regression analyses, restricted to children with low arsenic (As) exposure, none of the W-Mn exposures was associated with the children’s cognitive abilities. Stratifying by gender (p for interaction in general <0.081) showed that prenatal W-Mn (3 mg/L) was positively associated with cognitive ability measures in girls but not in boys. W-Mn at all time points was associated with an increased risk of conduct problems, particularly in boys (range 24–43% per mg/L). At the same time, the prenatal W-Mn was associated with a decreased risk of emotional problems [odds ratio (OR)=0.39 (95% CI: 0.19, 0.82)] in boys. In girls, W-Mn was mainly associated with low prosocial scores [prenatal W-Mn: OR=1.48 (95% CI: 1.06, 1.88)].
Elevated prenatal W-Mn exposure was positively associated with cognitive function in girls, whereas boys appeared to be unaffected. Early life W-Mn exposure appeared to adversely affect children's behavior. https://doi.org/10.1289/EHP631.
Preclinical and clinical research suggest that the α1 receptor antagonist prazosin reduces alcohol consumption. Furthermore, clinical studies indicate a role for prazosin in treating Post-Traumatic Stress Disorder (PTSD) symptoms and a recent trial suggested that pre-treatment blood pressure (BP) predicts therapeutic response for prazosin in PTSD patients. Whether pre-treatment BP may predict response to α1 blockers in alcohol-dependent (AD) patients is unknown. We previously reported a randomized controlled trial (RCT) where doxazosin, an α1 receptor antagonist with a more favorable pharmacokinetic profile than prazosin, reduced drinks per week (DPW) and heavy drinking days (HDD) in AD patients with a high family history density of alcoholism. In this study, we tested pre-treatment BP as another potentially valuable clinical moderator of doxazosin's response on alcohol consumption.
This was a double-blind placebo-controlled RCT testing doxazosin up to 16mg/day in AD treatment-seeking patients (N=41). The hypothesized moderator effect of baseline standing systolic and diastolic BP on DPW and HDD was tested.
With pre-treatment standing diastolic BP as a moderator, there were significant BP x medication interactions for both DPW [**p=0.009, d=0.80] and HDD [*p=0.018, d=1.11]. Post-hoc analyses indicated significant doxazosin effects in patients with higher standing BP in reducing both DPW and HDD.
These findings suggest that higher standing diastolic BP at baseline (pre-treatment) may represent a predictor of doxazosin's response on alcohol consumption in AD patients. These results further elucidate the possible efficacy and mechanisms of action of α1 receptor antagonism in AD individuals.
Copyright © 2017 Elsevier B.V. All rights reserved.
Alcohol use disorder; Aldosterone; Blood pressure; Cortisol; Doxazosin; α(1) Adrenoreceptor
A large proportion of individuals with alcohol problems do not seek psychological treatment, but access to such treatment could potentially be increased by delivering it over the Internet. Cognitive behavior therapy (CBT) is widely recognized as one of the psychological treatments for alcohol problems for which evidence is most robust. This study evaluated a new, therapist-guided internet-based CBT program (entitled ePlus) for individuals with alcohol use disorders.
Participants in the study (n = 13) were recruited through an alcohol self-help web site ( www.alkoholhjalpen.se ) and, after initial internet screening, were diagnostically assessed by telephone. Eligible participants were offered access to the therapist-guided 12-week program. The main outcomes were treatment usage data (module completion, treatment satisfaction) as well as glasses of alcohol consumed the preceding week, measured with the self-rated Timeline Followback (TLFB). Participant data were collected at screening (T0), immediately pre-treatment (T1), post-treatment (T2) and 3 months post-treatment (T3).
Most participants were active throughout the treatment and found it highly acceptable. Significant reductions in alcohol consumption with a large within-group effect size were found at the three-month follow-up. Secondary outcome measures of craving and self-efficacy, as well as depression and quality of life, also showed significant improvements with moderate to large within-group effect sizes.
Therapist-guided internet-based CBT may be a feasible and effective alternative for people with alcohol use disorders. In view of the high acceptability and the large within-group effect sizes found in this small pilot, a randomized controlled trial investigating treatment efficacy is warranted.
ClinicalTrials.gov ( NCT02384278 , February 26, 2015).
Alcohol dependence; Alcohol use disorders; Cognitive behavior therapy; Internet-based psychotherapy
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Cortical thickness; ENIGMA; FreeSurfer; MRI; PANSS; SANS; medial orbitofrontal cortex; negative symptoms; schizophrenia
The risk of certain psychiatric disorders is elevated among immigrants. To date, no population studies on immigrant health have addressed eating disorders. We examined whether risk of eating disorders in first- and second-generation immigrants differs from native-born Danes and Swedes.
All individuals born 1984-2002 (Danish cohort) and 1989-1999 (Swedish cohort) and residing in the respective country on their 10th birthday were included. They were followed up for the development of eating disorders based on out-patient and in-patient data.
The risks of all eating disorder types were lower among first-generation immigrants compared to the native populations: Incidence-rate ratio (95% confidence interval) was 0.39 (0.29, 0.51) for anorexia nervosa, 0.60 (0.42, 0.83) for bulimia nervosa, and 0.62 (0.47, 0.79) for other eating disorders in Denmark and 0.27 (0.21, 0.34) for anorexia nervosa, 0.30 (0.18, 0.51) for bulimia nervosa, and 0.39 (0.32, 0.47) for other eating disorders in Sweden. Likewise, second-generation immigrants by both parents were at lower risk, whereas those with only one foreign-born parent were not.
The decreased risk of eating disorders among immigrants is opposite to what has been observed for other psychiatric disorders, particularly schizophrenia. Possible explanations include buffering sociocultural factors and underdetection in health care.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
anorexia nervosa; bulimia nervosa; eating disorders; epidemiology; immigrants
Autism spectrum disorder (ASD) has been associated with gastrointestinal (GI) problems, but the nature of this association is unclear. Parents to siblings, concordant or discordant for ASD (N = 217), participated in a web survey covering mother's weight gain during pregnancy, maternal viral/bacterial infection and use of antibiotics, duration of breastfeeding, mode of delivery, birth weight and child GI problems. ASD was associated with GI problems and perinatal environmental risk, based on a summation of maternal infection and antibiotic use during pregnancy and/or the breastfeeding period. The association between GI problems and ASD remained within the sibling pairs (β = 1.23; p < .001) in the adjusted model. Our results indicate non-shared environmental effects on the ASD/GI association, but none of the factors examined explained the link.
Autism spectrum disorder; Breastfeeding; Cesarean section; Gastrointestinal problems; Infections; Siblings
Typically, early (pre-diagnostic) development in individuals later diagnosed with Rett syndrome (RTT) has been investigated retrospectively using parent reports, medical records and analysis of home videos. In recent years, prospective research designs have been increasingly applied to the investigation of early development in individuals with late phenotypical onset disorders, for example, autism spectrum disorder.
In this study, data collected by the Danish National Birth Cohort lent itself to prospective exploration of the early development of RTT, in particular early motor-, speech-language, and socio-communicative behaviors, mood, and sleep.
Despite limitations, this quasi prospective methodology proved promising. In order to add substantially to the body of knowledge, however, specific questions relating to peculiarites in early development could usefully be added to future cohort studies. As this involves considerable work, it may be more realistic to consider a set of indicators which point to a number of developmental disorders rather than to one.
Birth cohort; Rett syndrome; early development; longitudinal study; parent interviews; prodrome
Exposure-based cognitive behavior therapy (CBT) has been shown to be effective in the treatment of severe health anxiety, but little is known about mediators of treatment effect. The aim of the present study was to investigate mindful non-reactivity as a putative mediator of health anxiety outcome using data from a large scale randomized controlled trial. We assessed mindful non-reactivity using the Five Facets Mindfulness Questionnaire-Non-Reactivity scale (FFMQ-NR) and health anxiety with the Short Health Anxiety Inventory (SHAI). Participants with severe health anxiety (N=158) were randomized to internet-delivered exposure-based CBT or behavioral stress management (BSM) and throughout the treatment, both the mediator and outcome were measured weekly. As previously reported, exposure-based CBT was more effective than BSM in reducing health anxiety. In the present study, latent process growth modeling showed that treatment condition had a significant effect on the FFMQ-NR growth trajectory (α-path), estimate=0.18, 95% CI [0.04, 0.32], p=.015, indicating a larger increase in mindful non-reactivity among participants receiving exposure-based CBT compared to the BSM group. The FFMQ-NR growth trajectory was significantly correlated with the SHAI trajectory (β-path estimate=-1.82, 95% CI [-2.15, -1.48], p<.001. Test of the indirect effect, i.e. the estimated mediation effect (αβ) revealed a significant cross product of -0.32, which was statistically significant different from zero based on the asymmetric confidence interval method, 95% CI [-0.59, -0.06]. We conclude that increasing mindful non-reactivity may be of importance for achieving successful treatment outcomes in exposure-based CBT for severe health anxiety.
Cognitive behavior therapy; Exposure; Mediator; Mindful non-reactivity; Severe health anxiety
To evaluate the cost-effectiveness of a therapist-guided internet-delivered cognitive behaviour therapy (ICBT) intervention for adolescents with obsessive-compulsive disorder (OCD) compared with untreated patients on a waitlist.
Single-blinded randomised controlled trial.
A research clinic within the regular child and adolescent mental health service in Stockholm, Sweden.
Sixty-seven adolescents (12-17 years) with a Diagnostic and Statistical Manual of Mental Disorders Fifth Edition diagnosis of OCD.
Either a 12-week, therapist-guided ICBT intervention or a wait list condition of equal duration.
Cost data were collected at baseline and after treatment, including healthcare use, supportive resources, prescription drugs, prescription-free drugs, school absence and productivity loss, as well as the cost of ICBT. Health outcomes were defined as treatment responder rate and quality-adjusted life years gain. Bootstrapped mixed model analyses were conducted comparing incremental costs and health outcomes between the groups from the societal and healthcare perspectives.
Compared with waitlist control, ICBT generated substantial societal cost savings averaging US$-144.98 (95% CI -159.79 to -130.16) per patient. The cost reductions were mainly driven by reduced healthcare use in the ICBT group. From the societal perspective, the probability of ICBT being cost saving compared with waitlist control was approximately 60%. From the healthcare perspective, the cost per additional responder to ICBT compared with waitlist control was approximately US$78.
The results suggest that therapist-guided ICBT is a cost-effective treatment and results in societal cost savings, compared with patients who do not receive evidence-based treatment. Since, at present, most patients with OCD do not have access to evidence-based treatments, the results have important implications for the increasingly strained national and healthcare budgets. Future studies should compare the cost-effectiveness of ICBT with regular face-to-face CBT.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Internet; Obsessive-compulsive disorder; cognitive behavior therapy; cost-effectiveness; pediatric
Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.
Previous research has found strong associations between adolescents' hazardous alcohol use and their perception of peer behavior, as well as own spending money and a range of antisocial behaviors. However, there is insufficient evidence of gender-specific predictors among adolescents with elevated antisocial behavior and alcohol use to design effective selective interventions. The aims of this study were to test short-term predictors of Heavy Episodic Drinking (HED) and risk-use of alcohol among 12-18-year-old females and males with elevated externalizing and delinquent behavior, and alcohol use.
Eighty-five females, 77 males, and their parents, originally recruited for a parent intervention, were assessed at baseline and 6 months later with several validated instruments measuring externalizing and internalizing behavior, alcohol use, psychosocial distress, and delinquency.
The perception of peer drinking significantly predicted both genders' HED and risk-use, and also externalizing behavior predicted female risk-use. Rule-breaking behavior and social problems predicted both HED and risk-use among males, while rule-breaking predicted female HED and social problems predicted female risk-use. The parents' ratings of externalizing behavior predicted only their sons' risk-use. Lastly, no differences in prediction strength were found to be statistically significant differences between genders.
Females and males shared several predictors of hazardous alcohol use, and perception of peer drinking emerged as a strong predictor. This suggests that interventions may target both genders' hazardous use of alcohol, and should address peer-resisting skills.
Adolescents; Externalizing behavior; Heavy episodic drinking; Peers; Problem-behavior theory; Risk-use of alcohol
Clinical supervision by a senior therapist is a very common practice in psychotherapist training and psychiatric care settings. Though clinical supervision is advocated by most educational and governing institutions, the effects of clinical supervision on the supervisees' competence, e.g., attitudes, behaviors, and skills, as well as on treatment outcomes and other patient variables are debated and largely unknown. Evidence-based practice is advocated in clinical settings but has not yet been fully implemented in educational or clinical training settings. The aim of this systematic review is to synthesize and present the empirical literature regarding effects of clinical supervision in cognitive-behavioral therapy.
This study will include a systematic review of the literature to identify studies that have empirically investigated the effects of supervision on supervised psychotherapists and/or the supervisees' patients. A comprehensive search strategy will be conducted to identify published controlled studies indexed in the MEDLINE, EMBASE, PsycINFO, and Cochrane Library databases. Data on supervision outcomes in both psychotherapists and their patients will be extracted, synthesized, and reported. Risk of bias and quality of the included studies will be assessed systematically.
This systematic review will rigorously follow established guidelines for systematic reviews in order to summarize and present the evidence base for clinical supervision in cognitive-behavioral therapy and may aid further research and discussion in this area.
Clinical supervision, psychotherapy; Systematic review; Training
In 2016, the International Network on Brief Interventions for Alcohol & Other Drugs convened a meeting titled "Rethinking alcohol interventions in health care". The aims of the meeting were to synthesize recent evidence about screening and brief intervention and to set directions for research, practice, and policy in light of this evidence. Screening and brief intervention is efficacious in reducing self-reported alcohol consumption for some with unhealthy alcohol use, but there are gaps in evidence for its effectiveness. Because screening and brief intervention is not known to be efficacious for individuals with more severe unhealthy alcohol use, recent data showing the lack of evidence for referral to treatment as part of screening and brief intervention are alarming. While screening and brief intervention was designed to be a population-based approach, its reach is limited. Implementation in real world care also remains a challenge. This report summarizes practice, research, and policy recommendations and key research developments from our meeting. In order to move the field forward, a research agenda was proposed to (1) address evidence gaps in screening, brief intervention, and referral to treatment, (2) develop innovations to address severe unhealthy alcohol use within primary care, (3) describe the stigma of unhealthy alcohol use, which obstructs progress in prevention and treatment, (4) reconsider existing conceptualizations of unhealthy alcohol use that may influence health care, and (5) identify efforts needed to improve the capacity for addressing unhealthy alcohol consumption in all world regions.
Alcohol; Alcohol dependence; Brief intervention; Harmful alcohol use; Hazardous alcohol use; Health care; International; Referral to treatment; Research agenda; Screening
This study assessed the comparability of estimates of alcohol's harm to others across different administration modes in Swedish general population surveys. Harm was categorised as harm from strangers' drinking and harm from heavy drinkers known to the respondent.
Three surveys were conducted in 2011/2012 (n = 6841), including identical questions. One was based on self-administered postal or Web questionnaires, and two were based on computer-assisted telephone interviews of which one included a more ambitious procedure in terms of for example monetary incentives to the respondents. Pearson χ2 -tests were used to compare differences in the prevalence of harm. To estimate potential effects of survey mode, the samples were pooled, and multivariate Poisson regression models with mode as explanatory variable were used, adjusting for socio-demographic and behavioural factors.
Respondents in the two computer-assisted telephone interviews were more likely to report harm from strangers' drinking compared with respondents in the self-administered postal or Web questionnaires. However, no significant differences were found between survey modes concerning reports of harm from known people's drinking.
A survey mode based on interviews seems to facilitate reports of harm from strangers' drinking. This does not apply to reports of harm from known people's drinking. Therefore, the comparability of estimates of alcohol's harm to others between survey modes depends on the type of harm being studied. [Sundin E, Landberg J, Galanti MR, Room R, Ramstedt M. Are differences in population prevalence of alcohol's harmto others related to survey administration mode?
© 2017 Australasian Professional Society on Alcohol and other Drugs.
Sweden; administration mode; alcohol's harm to others; general population survey; prevalence
Alcohol-related problems at professional sporting events are of increasing concern and alarming reports are often reported in international media. Although alcohol consumption increases the risk for interpersonal violence, it is viewed as a focal element of large football events. Sweden has a long tradition of high public support for strict alcohol-control policies. However, little is known about public opinions on alcohol intoxication and the support for interventions to decrease intoxication at football events. The current study explored the public opinion towards alcohol use, intoxication and alcohol policies at professional football matches in Sweden.
A cross-sectional design was utilized and a random general population sample of 3503 adult Swedish residents was asked to participate in a web survey during 2016 (response rate 68%).
In total, 26% of the respondents supported alcohol sales at football events. Over 90% reported that obviously intoxicated spectators should be denied entrance or evicted from arenas. The support for regulations limiting alcohol availability varied with background factors such as gender, alcohol use and frequency of football event attendance.
There is a strong public consensus for strategies and policies to reduce alcohol sales and intoxication levels at football matches. This public support has implications for our preventive efforts and will facilitate the implementation of strategies and policy changes.
Public opinion Alcohol intoxication Football Sporting events AUDIT-C
The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that naltrexone would diminish the striatal dopamine release induced by amphetamine, which is considered an important mechanism behind many of its stimulant properties. We used positron emission tomography and the dopamine D2-receptor radioligand [11C]raclopride in healthy subjects to study the dopaminergic effects of an amphetamine injection after pretreatment with naltrexone or placebo. In a rat model, we used microdialysis to study the modulatory effects of naltrexone on dopamine levels after acute and chronic amphetamine exposure. In healthy humans, naltrexone attenuated the subjective effects of amphetamine, confirming our previous results. Amphetamine produced a significant reduction in striatal radioligand binding, indicating increased levels of endogenous dopamine. However, there was no statistically significant effect of naltrexone on dopamine release. The same pattern was observed in rats, where an acute injection of amphetamine caused a significant rise in striatal dopamine levels, with no effect of naltrexone pretreatment. However, in a chronic model, naltrexone significantly attenuated the dopamine release caused by reinstatement of amphetamine. Collectively, these data suggest that the opioid system becomes engaged during the more chronic phase of drug use, evidenced by the modulatory effect of naltrexone on dopamine release following chronic amphetamine administration. The importance of opioid-dopamine interactions in the reinforcing and addictive effects of amphetamine is highlighted by the present findings and may help to facilitate medication development in the field of stimulant dependence.
A relatively large number of studies have investigated the power of structural magnetic resonance imaging (sMRI) data to discriminate patients with schizophrenia from healthy controls. However, very few of them have also included patients with bipolar disorder, allowing the clinically relevant discrimination between both psychotic diagnostics. To assess the efficacy of sMRI data for diagnostic prediction in psychosis we objectively evaluated the discriminative power of a wide range of commonly used machine learning algorithms (ridge, lasso, elastic net and L0 norm regularized logistic regressions, a support vector classifier, regularized discriminant analysis, random forests and a Gaussian process classifier) on main sMRI features including grey and white matter voxel-based morphometry (VBM), vertex-based cortical thickness and volume, region of interest volumetric measures and wavelet-based morphometry (WBM) maps. All possible combinations of algorithms and data features were considered in pairwise classifications of matched samples of healthy controls (N = 127), patients with schizophrenia (N = 128) and patients with bipolar disorder (N = 128). Results show that the selection of feature type is important, with grey matter VBM (without data reduction) delivering the best diagnostic prediction rates (averaging over classifiers: schizophrenia vs. healthy 75%, bipolar disorder vs. healthy 63% and schizophrenia vs. bipolar disorder 62%) whereas algorithms usually yielded very similar results. Indeed, those grey matter VBM accuracy rates were not even improved by combining all feature types in a single prediction model. Further multi-class classifications considering the three groups simultaneously made evident a lack of predictive power for the bipolar group, probably due to its intermediate anatomical features, located between those observed in healthy controls and those found in patients with schizophrenia. Finally, we provide MRIPredict (https://www.nitrc.org/projects/mripredict/), a free tool for SPM, FSL and R, to easily carry out voxelwise predictions based on VBM images.
Parametric voxelwise analysis is a commonly used tool in neuroimaging, as it allows for identification of regions of effects in the absence of a strong a-priori regional hypothesis by comparing each voxel of the brain independently. Due to the inherent imprecision of single voxel measurements, spatial smoothing is performed to increase the signal-to-noise ratio of single-voxel estimates. In addition, smoothing compensates for imprecisions in anatomical registration, and allows for the use of cluster-based statistical thresholding. Smoothing has traditionally been applied in three dimensions, without taking the tissue types of surrounding voxels into account. This procedure may be suitable for subcortical structures, but is problematic for cortical regions for which grey matter often constitutes only a small proportion of the smoothed signal. New methods have been developed for cortical analysis in which voxels are sampled to a surface, and smoothing is restricted to neighbouring regions along the cortical grey matter in two dimensions. This procedure has recently been shown to decrease intersubject variability and bias of PET data. The aim of this study was to compare the variability, bias and test-retest reliability of volumetric and surface-based methods as they are applied in practice. Fifteen healthy young males were each measured twice using the dopamine D1 receptor radioligand [11C]SCH-23390, and analyses were performed at the level of individual voxels and vertices within the cortex. We found that surface-based methods yielded higher BPND values, lower coefficient of variation, less bias, better reliability and more precise estimates of parametric binding. All in all, these results suggest that surface-based methods exhibit superior performance to volumetric approaches for voxelwise analysis of PET data, and we advocate for their use when a ROI-based analysis is not appropriate.
This paper reports expert opinion on e-health intervention characteristics that enable effective communication of characteristics across the diverse field of e-health interventions. The paper presents a visualization tool to support communication of the defining characteristics.
An initial list of e-health intervention characteristics was developed through an iterative process of item generation and discussion among the 12 authors. The list was distributed to 123 experts in the field, who were emailed an invitation to assess and rank the items. Participants were asked to evaluate these characteristics in three separate ways.
A total of 50 responses were received for a response rate of 40.7%. Six respondents who reported having little or no expertise in e-health research were removed from the dataset. Our results suggest that 10 specific intervention characteristics were consistently supported as of central importance by the panel of 44 e-intervention experts. The weight and perceived relevance of individual items differed between experts; oftentimes, this difference is a result of the individual theoretical perspective and/or behavioral target of interest.
The first iteration of the visualization of salient characteristics represents an ambitious effort to develop a tool that will support communication of the defining characteristics for e-health interventions aimed to assist e-health developers and researchers to communicate the key characteristics of their interventions in a standardized manner that facilitates dialog.
Behavior; Guideline; Standardized reporting; Technology; e-Health intervention
Compulsive exercise (CE) has been proposed as significant in the etiology, development and maintenance of eating disorders (EDs), resulting in more severe and enduring pathology. However, few studies have investigated CE longitudinally in adolescents with EDs. We aimed to test if adolescents show the same associations between CE and other clinical variables as previous research has found in adults.
Three thousand one hundred sixteen girls and 139 boys from a clinical ED database were investigated regarding prevalence and frequency of CE and its relation to psychiatric symptoms, associated features and outcome. Denial of illness is common among adolescents and was therefore adjusted for.
Adjusted CE prevalence in girls was 44%, and CE was most prevalent in bulimia nervosa. As previously found in adults, those with CE scored significantly higher than non-CE on total ED severity, level of restriction and negative perfectionism. However, there were only minor differences between CE and non-CE patients on emotional distress, hyperactivity, suicidality and self-esteem. Among boys, adjusted CE prevalence was 38%, and CE boys scored significantly higher than non-CE on total ED severity. Initial CE did not influence 1-year outcome, although cessation of CE was associated with remission.
CE is a common clinical feature in adolescents with EDs and cessation is associated with remission. When controlling for denial of illness, CE had less detrimental impact than predicted. We recommend controlling for denial in studies on ED adolescents and further exploration of classification and treatment implications of CE.
Adolescents; Behavioral addiction; Compulsive exercise; Denial; Eating disorder
The purpose of this article is to explore learners' perceptions of using virtual patients in a behavioral medicine Massive Open Online Course (MOOCs) and thereby describe innovative ways of disseminating knowledge in health-related areas.
A 5-week MOOC on behavioral medicine was hosted on the edX platform. The authors developed two branched virtual patients consisting of video recordings of a live standardized patient, with multiple clinical decision points and narration unfolding depending on learners' choices. Students interacted with the virtual patients to treat stress and sleep problems. Answers to the exit survey and participant comments from the discussion forum were analyzed qualitatively and quantitatively.
In total, 19,236 participants enrolled in the MOOC, out of which 740 received the final certificate. The virtual patients were completed by 2317 and 1640 participants respectively. Among survey respondents (n = 442), 83.1% agreed that the virtual patient exercise was helpful. The qualitative analysis resulted in themes covering what it was like to work with the virtual patient, with subthemes on learner-centered education, emotions/eustress, game comparisons, what the participants learned, what surprised them, how confident participants felt about applying interventions in practice, suggestions for improvement, and previous experiences of virtual patients.
Students were enthusiastic about interacting with the virtual patients as a means to apply new knowledge about behavioral medicine interventions. The most common suggestion was to incorporate more interactive cases with various levels of complexity. Further research should include patient outcomes and focus on interprofessional aspects of learning with virtual patients in a MOOC.
Behavioral medicine; Case-based learning; Evaluation; MOOC; Qualitative content analysis; Virtual patient
Individuals who self-harm may have an increased risk of aggression toward others, but this association has been insufficiently investigated. More conclusive evidence may affect assessment, treatment interventions, and clinical guidelines.
To investigate the association between nonfatal self-harm and violent crime.
This population-based longitudinal cohort study, conducted from January 1, 1997, through December 31, 2013, studied all Swedish citizens born between 1982 and 1998 who were 15 years and older (N = 1 850 252). Individuals who emigrated from Sweden before the age of 15 years (n = 104 051) or immigrated to Sweden after the age of 13 years (ie, <2 years before the beginning of the follow-up; n = 22 009) were excluded. Data analysis was performed from April 21, 2016, to June 4, 2016.
Receipt of self-harm-associated clinical care.
Conviction of a violent crime according to the Swedish penal code.
The study cohort consisted of 1 850 525 individuals (950 382 males and 900 143 females), and the mean (SD) follow-up time was 8.1 (4.7) years (range, 0-17.0 years; minimum age, 15 years; maximum age, 32 years). During a mean follow-up period of 8.1 years, 55 185 individuals (3.0%) received clinical care for self-harm. The crude hazard ratio was 4.9 (95% CI, 4.8-5.0) for violent crime conviction in exposed individuals compared with the unexposed group. Women who self-harm were at particularly high risk for expressing violent behaviors. After adjustment for relevant psychiatric comorbidities and socioeconomic status, an almost doubled hazard of violent offense remained (hazard ratio, 1.8; 95% CI, 1.8-1.9).
Self-harm is associated with an increased risk of conviction for a violent offense in both sexes. The risk of violence, as well as the risk of suicide and self-harm, should be assessed among offending and self-harming individuals.
Alterations in the dopamine system are hypothesized to influence the expression of social anxiety disorder (SAD) symptoms. However, molecular imaging studies comparing dopamine function between patients and control subjects have yielded conflicting results. Importantly, while all previous investigations focused on the striatum, findings from activation and blood flow studies indicate that prefrontal and limbic brain regions have a central role in the pathophysiology. The objective of this study was to investigate extrastriatal dopamine D2-receptor (D2-R) availability in SAD. We examined 12 SAD patients and 16 healthy controls using positron emission tomography and the high-affinity D2-R radioligand [11C]FLB457. Parametric images of D2-R binding potential were derived using the Logan graphical method with cerebellum as reference region. Two-tailed one-way independent ANCOVAs, with age as covariate, were used to examine differences in D2-R availability between groups using both region-based and voxel-wise analyses. The region-based analysis showed a medium effect size of higher D2-R levels in the orbitofrontal cortex (OFC) in patients, although this result did not remain significant after correction for multiple comparisons. The voxel-wise comparison revealed elevated D2-R availability in patients within OFC and right dorsolateral prefrontal cortex after correction for multiple comparisons. These preliminary results suggest that an aberrant extrastriatal dopamine system may be part of the disease mechanism in SAD.
Dopamine; Dopamine D2; Phobic disorders; Positron-Emission tomography; Prefrontal cortex; Receptors
Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia.
This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness.
Positive symptom severity was negatively related to STG thickness in both hemispheres (left: βstd = -0.052; P = 0.021; right: βstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness.
Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
ENIGMA; FreeSurfer; MRI; cortical thickness; positive and negative syndrome scale; positive symptoms; scale for the assessment of positive symptoms; schizophrenia; superior temporal gyrus
To investigate the risk of suicide, unnatural death and all-cause death in university students compared with non-students, taking previous educational attainment into account.
Open cohort study of all residents aged 18-39 and living in Sweden at any time between 1 January 1993 and 31 December 2011.
We linked data from national registers and calculated person-years during university studies for three time periods (1993-1999, 2000-2005 and 2006-2011). Time as non-student was calculated and categorised according to attained educational level. Incidence rate ratios (IRR) with 95% CIs were calculated with Poisson regression models, controlling for age and period.
The cohort consisted of 5 039 419 individuals, 51% men and 49% women.
Incidence of suicide (International Classification of Diseases (ICD)-9: E950-E959, ICD-10: X60-X84) or death with undetermined intent (ICD-9: E980-E989, ICD-10: Y10-Y34), unnatural death (ICD-9: E800-E999 and ICD-10: V01-Y99) and all-cause death.
A total of 7316 deaths due to suicide were identified, of which 541 were registered among university students. The risk of suicide was twofold during ongoing university studies compared with when having attained university education, IRR 2.37 (95% CI 2.07 to 2.72) in men and IRR 2.15 (95% CI 1.77 to 2.61) in women.
Having ongoing university studies was associated with a higher risk of suicide compared with having attained university-level education. This finding highlights the importance of achieving a deeper understanding of suicidal behaviour during years at university. Further studies should assess risk factors for suicide and suicidal behaviour in university students.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
PUBLIC HEALTH; mortality; university students
Earlier research has investigated the association between parental separation and long-term health outcomes among offspring, but few studies have assessed the potentially moderating role of mental health status in adolescence. The aim of this study was to analyze whether parental separation in childhood predicts depression in adulthood and whether the pattern differs between individuals with and without earlier depression.
A community-based sample of individuals with adolescent depression in 1991-93 and matched non-depressed peers were followed up using a structured diagnostic interview after 15 years. The participation rate was 65% (depressed n = 227; non-depressed controls n = 155). Information on parental separation and conditions in childhood and adolescence was collected at baseline. The outcome was depression between the ages 19-31 years; information on depression was collected at the follow-up diagnostic interview. The statistical method used was binary logistic regression.
Our analyses showed that depressed adolescents with separated parents had an excess risk of recurrence of depression in adulthood, compared with depressed adolescents with non-separated parents. In addition, among adolescents with depression, parental separation was associated with an increased risk of a switch to bipolar disorder in adulthood. Among the matched non-depressed peers, no associations between parental separation and adult depression or bipolar disorder were found.
Parental separation may have long-lasting health consequences for vulnerable individuals who suffer from mental illness already in adolescence.
Adolescence; Bipolar; Depression; Divorce; Family structure; Family type; Prospective
This is the third in a series of four cross-cultural empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF, and Children and Youth version, ICF(-CY) Core Sets for Attention-Deficit Hyperactivity Disorder (ADHD). To explore the perspectives of individuals diagnosed with ADHD, self-advocates, immediate family members and professional caregivers on relevant areas of impairment and functional abilities typical for ADHD across the lifespan as operationalized by the ICF(-CY). A qualitative study using focus group discussions or semi-structured interviews of 76 participants, divided into 16 stakeholder groups. Participants from five countries (Brazil, India, Saudi Arabia, South Africa and Sweden) were included. A deductive qualitative content analysis was conducted to extract meaningful functioning and disability concepts from verbatim material. Extracted concepts were then linked to ICF(-CY) categories by independent researchers using a standardized linking procedure. In total, 82 ICF(-CY) categories were identified, of which 32 were related to activities and participation, 25 to environmental factors, 23 to body functions and 2 to body structures. Participants also provided opinions on experienced positive sides to ADHD. A high level of energy and drive, creativity, hyper-focus, agreeableness, empathy, and willingness to assist others were the most consistently reported strengths associated with ADHD. Stakeholder perspectives highlighted the need to appraise ADHD in a broader context, extending beyond diagnostic criteria into many areas of ability and disability as well as environmental facilitators and barriers. This qualitative study, along with three other studies (comprehensive scoping review, expert survey and clinical study), will provide the scientific basis to define ICF(-CY) Core Sets for ADHD, from which assessment tools can be derived for use in clinical and research setting, as well as in health care administration.
ADHD; Assessment; DSM; ICD; Impairment; Neurodevelopmental disorder; Psychiatry; Qualitative study; Quality of life
Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.
Bereavement after spousal suicide has been linked to mental disorders; however, a comprehensive assessment of the effect of spousal suicide is needed.
To determine whether bereavement after spousal suicide was linked to an excessive risk of mental, physical, and social health outcomes when compared with the general population and spouses bereaved by other manners.
This nationwide, register-based cohort study conducted in Denmark of 6.7 million individuals aged 18 years and older from 1980 to 2014 covered more than 136 million person-years and compared people bereaved by spousal suicide with the general population and people bereaved by other manners of death. Incidence rate ratios were calculated using Poisson regressions while adjusting for sociodemographic characteristics and the presence of mental and physical disorders.
Mental disorders (any disorder, mood, posttraumatic stress disorder, anxiety, alcohol use disorders, drug use disorders, and self-harm); physical disorders (cancers, diabetes, sleep disorder, cardiovascular diseases, chronic lower respiratory tract diseases, liver cirrhosis, and spinal disc herniation); causes of mortality (all-cause, natural, unintentional, suicide, and homicide); social health outcomes; and health care use.
The total study population included 3 491 939 men, 4814 of whom were bereaved by spousal suicide, and 3 514 959 women, 10 793 of whom were bereaved by spousal suicide. Spouses bereaved by a partner's suicide had higher risks of developing mental disorders within 5 years of the loss (men: incidence rate ratio, 1.8; 95% CI, 1.6-2.0; women: incidence rate ratio, 1.7; 95% CI, 1.6-1.8) than the general population. Elevated risks for developing physical disorders, such as cirrhosis and sleep disorders, were also noted as well as the use of more municipal support, sick leave benefits, and disability pension funds than the general population. Compared with spouses bereaved by other manners of death, those bereaved by suicide had higher risks for developing mental disorders (men: incidence rate ratio, 1.7; 95% CI, 1.5-1.9; women: incidence rate ratio, 2.0; 95% CI, 1.9-2.2), suicidal behaviors, mortality, and municipal support. Additionally, a higher level of mental health care use was noted.
Exposure to suicide is stressful and affects the bereaved spouse on a broad range of outcomes. The excess risks of mental, physical, and social health outcomes highlight a need for more support directed toward spouses bereaved by suicide.
Online gambling, encompassing a wide variety of activities and around-the-clock access, can be a potential risk factor for gamblers who tend to gamble excessively. Yet, the advent of online gambling has enabled responsible gambling (RG) features that may help individuals to limit their gambling behaviour. One of these features is RG tools that track gamblers' behaviour, performs risk assessments and provides advice to gamblers. This study investigated users' views and experiences of the RG tool Playscan from a qualitative perspective using a semi-structured interview. The tool performs a risk assessment on a three-step scale (low, medium and high risk). Users from every risk category were included. Twenty interviews were carried out and analysed using thematic analysis. Two main themes with associated sub-themes were identified: "Usage of Playscan and the gambling site" and "Experiences of Playscan". Important experiences in the sub-themes were lack of feedback from the tool and confusion when signing up to use Playscan. These experiences counteracted positive attitudes that should have promoted usage of the tool. Providing more feedback directly to users is a suggested solution to increase usage of the RG tool.
Feedback; Qualitative study; Responsible gambling tool; Thematic analysis; Usage
The serotonin 1B receptor has recently received more interest as a possible new target for pharmacological treatment of psychiatric disorders. However, the exact mechanisms of action remain unclear. This study aimed to examine the binding distribution and levels of the serotonin 1B receptor in-depth in the anterior cingulate cortex (ACC) and provide more insight in its functional role in bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). Serotonin 1B receptor binding distribution was visualized with high resolution autoradiography (ARG), using the radioligand [3H]AZ10419369, in postmortem ACC tissue from patients diagnosed with BD (n=14), MDD (n=12), SZ (n=13) and healthy subjects (n=13). Moreover, a quantification of receptor binding was made with ARG, in relation to patient group, age and gender. In all subject groups a significantly higher specific binding of serotonin 1B receptor was measured in the outer ACC layers compared to the inner ACC layers. Correlation analysis with ARG binding patterns of several radioligands resulted in a significant correlation with glutamatergic N-methyl-D-aspartate receptor binding in the outer layers. No significant difference was found between subject groups in binding levels and distribution. In female subjects a significantly lower receptor binding was found than in male subjects, which was most profound in patients diagnosed with MDD. The binding distribution of the serotonin 1B receptor found in this study supports a role in glutamate transmission in the ACC and was not shown to be significantly altered in BD, MDD or SZ. A gender difference in serotonin 1B receptor binding was found.
Anterior cingulate cortex; Autoradiography; Bipolar disorder; Major depressive disorder; Schizophrenia; Serotonin 1B receptor
The use of biomarkers (BMs) for accurate diagnosis of Alzheimer's disease (AD) has been proposed by recent diagnostic criteria; however, their maturity is not sufficient to grant implementation in the clinical routine. A proper diagnostic process requires not only confirmation of the disease but also the exclusion of similar disorders entering differential diagnosis, like dementia with Lewy bodies (DLB). This review is aimed at evaluating the clinical validity of 123I-ioflupane brain single photon emission tomography and 123I-MIBG cardiac scintigraphy as imaging BMs for DLB. For this purpose, we used an adapted version of the 5-phase oncology framework for BMs development. A review of the literature was conducted using homogenous search criteria with other BMs addressed in parallel reviews. Results of our literature search showed that the rationale for the use of both BMs in the differential diagnosis of DLB and AD is strong (phase 1) and that they allow a good discrimination ability (phase 2), but studies investigating BMs distribution antemortem and postmortem on pathology are lacking. Moreover, thresholds for test positivity have not been defined for 123I-MIBG. The 2 BMs have not been yet assessed in early phases of DLB and AD (phase 3). No phase 4 and phase 5 studies have so far been carried out. This review highlights the priorities to address in future investigations to enable the proper use of 123I-ioflupane and 123I-MIBG for the differential diagnosis of dementia.
(123)I-MIBG; (123)I-ioflupane; Alzheimer's disease; Biomarker-based diagnosis; Dementia with Lewy bodies; Differential diagnosis; Dopaminergic imaging; Noradrenergic imaging
The use of biomarkers has been proposed for diagnosing Alzheimer's disease in recent criteria, but some biomarkers have not been sufficiently investigated to justify their routine clinical use. Here, we evaluate in a literature review the clinical validity of amyloid positron emission tomography (PET) imaging using a structured framework developed for the assessment of oncological biomarkers. Homogenous criteria have been addressed in reviews of other Alzheimer's disease biomarkers. There is adequate evidence that the main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved. The aims of phase 3 (early detection ability) have been partly achieved, while phase 4 studies (performance in representative mild cognitive impairment patients) are currently ongoing. Phase 5 studies (quantification of impact and costs) are still to come. This review highlights the priorities to be pursued to enable the proper use of amyloid PET imaging in a clinical setting. Future investigations will primarily be large, phase 4 studies that will assess the utility of amyloid PET imaging in routine clinical practice.
5-Phases; Alzheimer's disease; Amyloid; Biomarker; Biomarker-based diagnosis; Clinical validity; Development; Early diagnosis; Neuroimaging; Positron emission tomography
The use of Alzheimer's disease (AD) biomarkers is supported in diagnostic criteria, but their maturity for clinical routine is still debated. Here, we evaluate brain fluorodeoxyglucose positron emission tomography (FDG PET), a measure of cerebral glucose metabolism, as a biomarker to identify clinical and prodromal AD according to the framework suggested for biomarkers in oncology, using homogenous criteria with other biomarkers addressed in parallel reviews. FDG PET has fully achieved phase 1 (rational for use) and most of phase 2 (ability to discriminate AD subjects from healthy controls or other forms of dementia) aims. Phase 3 aims (early detection ability) are partly achieved. Phase 4 studies (routine use in prodromal patients) are ongoing, and only preliminary results can be extrapolated from retrospective observations. Phase 5 studies (quantify impact and costs) have not been performed. The results of this study show that specific efforts are needed to complete phase 3 evidence, in particular comparing and combining FDG PET with other biomarkers, and to properly design phase 4 prospective studies as a basis for phase 5 evaluations.
5-Phases; Alzheimer's disease; Biomarker-based diagnosis; Biomarkers development; Early diagnosis; FDG PET
Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.
Phosphodiesterase 10A enzyme (PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington´s disease (HD). PDE10A is expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D2/3 receptors (D2/3 R). The aim of this study was to examine the availability of PDE10A enzyme in relation with age and gender and to compare those changes with those related to D2/3 R and volumes in different regions of the basal ganglia. As a secondary objective we examined the relative distribution of D2/3 R and PDE10A enzyme in the striatum and globus pallidus. Forty control subjects (20F/20M; age: 44±11y, age range 27-69) from an ongoing positron emission tomography (PET) study in HD gene expansion carriers were included. Subjects were examined with PET using the high-resolution research tomograph (HRRT) and with 3T magnetic resonance imaging (MRI). The PDE10A radioligand 18F-MNI-659 and D2/3 R radioligand 11C-raclopride were used. The outcome measure was the binding potential (BPND) estimated with the two-tissue compartment model (18F-MNI-659) and the simplified reference tissue model (11C-raclopride) using the cerebellum as reference region. The PET data were corrected for partial volume effects. In the striatum, PDE10A availability showed a significant age-related decline that was larger compared to the age-related decline of D2/3 R availability and to the age-related decline of volumes measured with MRI. In the globus pallidus, a less pronounced decline of PDE10A availability was observed, whereas D2/3 R availability and volumes seemed to be rather stable with aging. The distribution of the PDE10A enzyme was different from the distribution of D2/3 R, with higher availability in the globus pallidus. These results indicate that aging is associated with a considerable physiological reduction of the availability of PDE10A enzyme in the striatum. Moreover as result of the analysis, in the striatum for both the molecular targets, we observed a gender effect with higher BPND the female group.
Research regarding psychological risk factors for reduced weight loss after bariatric surgery has yielded mixed results, especially for variables measured prior to surgery. More profound personality factors have shown better promise and one such factor that may be relevant in this context is time perspective, i.e., the tendency to focus on present or future consequences. The aim of this study was to investigate the predictive value of time perspective for 12-month weight loss after Roux-en-Y gastric bypass surgery.
A total of 158 patients were included and completed self-report instruments prior to surgery. Weight loss was measured after 12 months by medical staff. Background variables as well as self-reported disordered eating, psychological distress, and time perspective were analyzed with regression analysis to identify significant predictors for 12-month weight loss.
The mean BMI loss at 12 months was 14 units, from 45 to 30 kg/m2. Age, sex, and time perspective could significantly predict weight loss but only male sex and self-reported hedonism were independent risk factors for reduced weight loss in the final regression model.
In this study, self-reported hedonistic time perspective proved to be a better predictor for 12-month weight loss than symptoms of disordered eating and psychological distress. It is possible that a hedonistic tendency of focusing on immediate consequences and rewards is analogous to the impaired delay discounting seen in previous studies of bariatric surgery candidates. Further studies are needed to identify whether these patients may benefit from extended care and support after surgery.
Bariatric surgery; Hedonism; Personality; Risk factors; Time perspective; Weight loss
University students in a study on estimated blood alcohol concentration (eBAC) feedback apps were offered participation in a second study, if reporting continued excessive consumption at 6-week follow-up. This study evaluated the effects on excessive alcohol consumption of offering access to an additional skills training app.
A total of 186 students with excessive alcohol consumption were randomized to an intervention group or a wait list group. Both groups completed online follow-ups regarding alcohol consumption after 6 and 12 weeks. Wait list participants were given access to the intervention at 6-week follow-up. Assessment-only controls (n = 144) with excessive alcohol consumption from the ongoing study were used for comparison.
The proportion of participants with excessive alcohol consumption declined in both intervention and wait list groups compared to controls at first (p < 0.001) and second follow-ups (p = 0.054). Secondary analyses showed reductions for the intervention group in quantity of drinking at first follow-up (-4.76, 95% CI [-6.67, -2.85], Z = -2.09, p = 0.037) and in frequency of drinking at both follow-ups (-0.83, 95% CI [-1.14, -0.52], Z = -2.04, p = 0.041; -0.89, 95% CI [-1.16, -0.62], Z = -2.12, p = 0.034). The odds ratio for not having excessive alcohol consumption among men in the intervention group compared to male controls was 2.68, 95% CI [1.37, 5.25] (Z = 2.88, p = 0.004); the figure for women was 1.71, 95% CI [1.11, 2.64] (Z = 2.41, p = 0.016).
Skills training apps have potential for reducing excessive alcohol use among university students. Future research is still needed to disentangle effects of app use from emailed feedback on excessive alcohol consumption and study participation.
Alcohol abuse; Brief intervention; College; Mobile phone; Problem drinking; Randomized controlled trial; Relapse prevention; Smartphone; University; eHealth; mHealth
Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders.
The study examined the ability of the EDI-2 to classify empirically valid and clinically meaningful change using clinical significance and the Reliable Change Index (CS/RCI), and compared CS/RCI to classification based on diagnostic change. Eating disorder (ED) patients (N=363) were assessed at intake and after 36months on measures of ED and psychiatric symptoms, self-image, interpersonal relationships, treatment satisfaction and general outcome. Patients were categorized using a four-way classification scheme as "Deteriorated", "Unchanged", "Improved" or "No ED"; and using a two-way classification scheme as either in remission or not in remission. Compared to similar two- and four-way classification based on diagnostic change, CS/RCI using the EDI-2 total score demonstrated greatest overall utility in explaining outcome variance. The EDI-2 can generate empirically valid and clinically meaningful classification of change. Systematic application of CS/RCI using the EDI-2 benefits both clinicians and researchers by providing a simple, clinically relevant, scientifically robust, and cost-effective means of classifying outcome. It may be especially relevant in alerting clinicians to problem cases in need of additional or alternative treatment strategies.
Assessment; Classification; Clinical significance; Eating Disorders Inventory version 2; Outcome; Reliable change
Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [11C]PBR28. Gray matter (GM) volume of distribution (VT) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [11C]PBR28 binding, and gender. There was a significant reduction of [11C]PBR28 VT in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM VT and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.
Schizophrenia (SZ) and Bipolar Disorder (BD) are associated with deficits in both timing and cognitive control functions. However, the underlying neurological dysfunctions remain poorly understood. The main goal of this study was to identify brain structures activated both by increases in cognitive activity and during timing tasks in patients with SZ and BD relative to controls. We conducted two signed differential mapping (SDM) meta-analyses of functional magnetic resonance imaging studies assessing the brain response to increasing levels of cognitive difficulty: one concerned SZ, and the other BD patients. We conducted a similar SDM meta-analysis on neuroimaging of timing in SZ (no studies in BD could be included). Finally, we carried out a multimodal meta-analysis to identify common brain regions in the findings of the two previous meta-analyses. We found that SZ patients showed hypoactivation in timing-related cortical-subcortical areas. The dysfunction observed during timing partially coincided with deficits for cognitive control functions. We hypothesize that a dysfunctional temporal/cognitive control network underlies the persistent cognitive impairment observed in SZ.
Bipolar disorder; Cognitive control; Functional neuroimaging; SDM-meta-analysis; Schizophrenia; Timing
The Drinking Motives Questionnaire measures motives for alcohol consumption on four subscales. Coping with negative affect and enhancement of positive affect have been shown to be associated with high levels of alcohol consumption and alcohol-related problems. Few studies exist concerning drinking motives among treatment-seeking patients. The aims of the study were to investigate the factor structure of the shortened-form of the revised Drinking Motives Questionnaire, map main drinking motives, explore group differences in motives due to sex, age, level of drinking problems, and symptoms of depression/anxiety and to investigate whether different drinking motives predict alcohol-related problems in this group. There were 274 treatment-seeking patients recruited from four addiction treatment clinics in Sweden. The shortened-form of the revised Drinking Motives Questionnaire was administered in conjunction with a regular visit to the clinics together with measures of degree of alcohol-related problems, psychiatric symptoms, and demographic factors. Main drinking motives were identified. A confirmatory factor analysis was run to confirm the factor structure of the shortened-form of the revised Drinking Motives Questionnaire. A logistic regression using the Enter method was performed to investigate associations between predictors and Alcohol Use Disorder Identification Test scores. The results confirmed the four-factor structure reported in studies on non-treatment-seeking individuals. Coping was the most commonly expressed motive. Not previously found in a clinical sample, the results showed that coping motives, together with being male and having elevated anxiety scores, were associated to Alcohol Use Disorder Identification Test scores indicative of alcohol dependence. The shortened-form of the revised Drinking Motives Questionnaire is a brief and valid instrument that holds potential for clinical use in mapping drinking motives among treatment seekers.
DMQ-R-SF; Motives for drinking; alcohol dependence; coping; treatment seekers
The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections). First, differences in early medical events were investigated using multisource medical records in pairs qualitatively discordant for ASD. The significant intra-pair differences identified were then tested in relation to autistic traits in the remaining sample of 100 pairs, applying generalized estimating equations analyses. Significant association of the intra-pair differences in the MZ pairs were found for the cumulative load of early medical events and clinical ASD (Z=-2.85, P=0.004) and autistic traits (β=78.18, P=0.002), as well as infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness), when controlling for intelligence quotient and attention deficit hyperactivity disorder comorbidity. The cumulative load of early medical events in general, and infant dysregulation in particular, may index children at risk of ASD owing to non-shared environmental contributions. In clinical practice, these findings may facilitate screening and early detection of ASD.
Adherence to treatment homework is associated with positive outcomes in behavioral psychotherapy but compliance to assignments is still often moderate. Whether adherence can be predicted by different types of motivation for the task and whether motivation plays different roles in face-to-face compared to online psychotherapy is unknown. If models of motivation, such as Self-determination theory, can be used to predict patients' behavior, it may facilitate further research into homework promotion. The aims of this study were, therefore, to investigate whether motivation variables could predict adherence to a prescribed assignment in face-to-face and online interventions using a psychotherapy analog model.
A total of 100 participants were included in this study and randomized to either a face-to-face or online intervention. Participants in both groups received a psychoeducation session and were given an assignment for the subsequent week. The main outcome measurements were self-reported motivation and adherence to the assignment.
Participant in the face-to-face condition reported significantly higher levels of motivation and showed higher levels of adherence compared to participants in the online condition. Adherence to the assignment was positively associated with intrinsic motivation and intervention credibility in the whole sample and especially in the online group.
This study shows that intrinsic motivation and intervention credibility are strong predictors of adherence to assignments, especially in online interventions. The results indicate that intrinsic motivation may be partly substituted with face-to-face contact with a therapist. It may also be possible to identify patients with low motivation in online interventions who are at risk of dropping out. Methods for making online interventions more intrinsically motivating without increasing external pressure are needed.
clinicaltrials.gov NCT02895308 . Retrospectively registered 30 August 2016.
Adherence; Homework assignments; Internet; Motivation; Psychoeducation
Ketamine administration is a well-established approach to mimic experimentally some aspects of schizophrenia. Adult neurogenesis dysregulation is associated with psychiatric disorders, including schizophrenia. The potential role of neurogenesis in the ketamine-induced phenotype is largely unknown. Recent results from human genetic studies have shown the pituitary adenylate cyclase-activating polypeptide (PACAP) gene is a risk factor for schizophrenia. Its potential role on the regulation of neurogenesis in experimental model of schizophrenia remains to be investigated. We aimed to determine whether ketamine affects the viability of adult neural stem cells (NSC). We also investigated whether the detrimental effect mediated by ketamine could be counteracted by PACAP. NSCs were isolated from the subventricular zone of the mouse and exposed to ketamine with/without PACAP. After 24 hours, cell viability, potential involvement of apoptosis, endoplasmic reticulum (ER) stress, mTOR and AMPA pathway activation were assessed by quantitative RT-PCR and Western blot analysis. We show that ketamine impairs NSC viability in correlation with increased apoptosis, ER stress and mTOR activation. The results also suggest that the effect of ketamine occurs via AMPA receptor activation. Finally, we show that PACAP counteracted the decreased NSC viability induced by ketamine via the specific activation of the PAC-1 receptor subtype. Our study shows that the NSC viability may be negatively affected by ketamine with putative importance for the development of a schizophrenia phenotype in the ketamine induced animal model of schizophrenia. The neuroprotective effect via PAC-1 activation suggests a potentially novel pharmacological target for the treatment of schizophrenia, via neurogenesis normalization.
WHAT IS KNOWN ON THE SUBJECT?: The Depression, Anxiety and Stress Scale-21 (DASS-21) is a widely used measurement for psychological symptoms and distress. Some previous studies have shown that the DASS-21 can accurately measure symptoms of anxiety, depression and stress, while other studies have indicated that the DASS-21 mainly measures overall distress. The factor structure of the DASS-21 is important and debated since if affects interpretations of findings. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: In this study, the DASS-21 was translated into Swedish and evaluated in three diverse samples. The DASS-21 subscales of Depression and Anxiety correlated significantly with corresponding criteria instruments. The DASS-21 Stress subscale showed more diverse associations with psychological distress. The analyses supported a bifactor model of the DASS-21 with three specific factors of depression, anxiety and stress as well as a general distress factor. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The results show that the DASS-21 may be used to measure unique symptoms of depression, anxiety and, with some caveat, stress as well as overall psychological distress. This study confirms that the DASS-21 is theoretically sound instrument that is feasible for both research and clinical practice. The DASS-21 can be an accessible tool for screening and evaluation in first-line mental health services.
Introduction There is a constant need for theoretically sound and valid self-report instruments for measuring psychological distress. Previous studies have shown that the Depression, Anxiety and Stress Scale-21 (DASS-21) is theoretically sound, but there have been some inconsistent results regarding its factor structure. Aims The aim of the present study was to investigate and elucidate the factor structure and convergent validity of the DASS-21. Methods A total of 624 participants recruited from student, primary care and psychotherapy populations. The factor structure of the DASS-21 was assessed by confirmatory factor analyses and the convergent validity by investigating its unique correlations with other psychiatric instruments. Results A bifactor structure with depression, anxiety, stress and a general factor provided the best fit indices for the DASS-21. The convergent validity was adequate for the Depression and Anxiety subscales but more ambiguous for the Stress subscale. Discussion The present study overall supports the validity and factor structure of the DASS-21. Implications for practice The DASS-21 can be used to measure symptoms of depression and anxiety as well as overall distress. It can be useful for mental health nurses, and other first-line psychiatric professionals, in need of a short, feasible and valid instrument in everyday care.
© 2017 John Wiley & Sons Ltd.
anxiety; depression; distress; psychometric; screening; stress
The study aimed to validate the Arabic version of the Drug Use Disorders Identification Test (DUDIT) by (1) assessing its factor structure, (2) determining structural validity, (3) evaluating item-total and inter-item correlation, and (4) assessing its predictive validity.
The study population included 169 prison inmates, 51 patients with clinical diagnosis of substance used disorder, and 53 students (N = 273). All participants completed the self-report version of the Arabic DUDIT. After exploratory factor analysis, internal consistency of the Arabic DUDIT was determined and external validation was performed.
Principal factor analysis showed that Arabic DUDIT exhibited only one factor, which explained 66.9% of the variance. Reliability based on Cronbach's alpha was .95. When compared to the DSM-IV substance use disorder diagnosis in a clinical sample, DUDIT had an area under the curve (AUC) of .98, with a sensitivity of .98 and a specificity of .90.
The Arabic version of DUDIT is a valid and reliable tool for screening for drug use in Arabic-speaking countries.
Arabic; DUDIT; Drug use; MeSHe study; Psychometric properties; Screening
Phosphodiesterase 10A (PDE10A) is an enzyme highly enriched in the striatal medium spiny neurons. It is involved in the regulation of cytoplasmic levels of cAMP and cGMP and signaling within the basal ganglia. This study with PDE10A radioligand [18F]MNI-659 was designed to measure the enzyme occupancy of PF-02545920 in 8 healthy male volunteers (48 ± 4 years) after a single oral dose (10 mg or 20 mg) and to evaluate safety and tolerability. Arterial blood sampling was performed to obtain a metabolite-corrected plasma input function for the quantification of [18F]MNI-659 binding to PDE10A. The occupancy of PF-02545920 was calculated with two different methods: In Method 1, [18F]MNI-659 enzyme occupancy was calculated from the estimates of binding potential, using the cerebellum as a reference region; in Method 2, occupancy was estimated from the slope of the revised Lassen's plot. Serum concentrations of PF-02545920 were measured to determine the relationship between concentration and occupancy. Based on Method 1, striatal PDE10A occupancy increased with increasing PF-02545920 dose: 14-27% at 10 mg dose (N = 4) and 45-63% at 20 mg dose (N = 3). Comparable occupancies were observed using Lassen's plot Method 2: 10 mg: 14-37%; 20 mg: 46-55%. The relationship between exposure and occupancy was best described using an Emax model. The serum concentration associated with 50% occupancy was estimated to be 93.2 ng/mL. Single oral doses of 10 mg or 20 mg of PF-02545920 were safe and well tolerated in healthy male volunteers [NCT# 01918202].
Enzyme occupancy; Healthy volunteer; PDE10 inhibitor; PF-02545920; Positron emission tomography; Radioligand [(18)F]MNI-659; Single dose
Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear.
To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables.
PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked.
Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder.
Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies.
Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes.
D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.
Despite meta-analytic evidence for the association between attention-deficit/hyperactivity disorder (ADHD) and overweight/obesity, the mechanisms underlying the association are yet to be fully understood.
By linking multiple Swedish national and regional registers, we identified 472,735 index males born during 1973-1992, with information on body weight and height directly measured before they were conscripted for military service. We further identified 523,237 full siblings born during 1973-2002 for the index males. All individuals were followed up from their third birthday to December 31, 2009 for ADHD diagnosis. Logistic regression models were used to estimate the association between overweight/obesity in index males and ADHD in their full siblings.
Siblings of index males with overweight/obesity had increased risk for ADHD (overweight: OR = 1.14, 95% CI = 1.05-1.24; obesity: OR = 1.42, 95% CI = 1.24-1.63), compared with siblings of index males with normal weight. The results were adjusted for birth year of the index male and sex of the sibling. After further adjustment for ADHD status of the index male, the familial coaggregation remained significant (overweight: OR = 1.13, 95% CI = 1.04-1.22; obesity: OR = 1.38, 95% CI = 1.21-1.57). The results were similar across sex of the siblings.
Attention-deficit/hyperactivity disorder and overweight/obesity share familial risk factors, which are not limited to those causing overweight/obesity through the mediation of ADHD. Future research aiming at identifying family-wide environmental risk factors as well as common pleiotropic genetic variants contributing to both traits is warranted.
© 2017 Association for Child and Adolescent Mental Health.
Attention-deficit/hyperactivity disorder; family factors; genetics; obesity
The aim of the present study was to explore patients' experiences of participating in a self-admission program at a specialist eating disorders clinic. Sixteen adult program participants with a diagnosis of anorexia nervosa were interviewed at 6 months about their experiences in the self-admission program. A qualitative content analysis approach was applied to identify recurring themes. Four themes were identified: Agency and Flexibility, Functions, Barriers, and Applicability. Participants used self-admission to boost healthy behaviors, to prevent deterioration, to forestall the need for longer periods of hospitalizations, and to get a break from overwhelming demands. Quick access to brief admissions provides a safety net that can increase feelings of security in everyday life, even for patients who do not actually make use of the opportunity to self-admit. It also provided relief to participants' relatives. Furthermore, participants experienced that self-admission may foster agency and motivation. However, the model also requires a certain level of maturity and an encouraging environment to overcome barriers that could otherwise hinder optimal use, such as ambivalence in asking for help. Informants experienced that self-admission could allow them to gain greater insight into their disease process, take greater responsibility for their recovery, and transform their health care from crisis-driven to proactive. By offering a shift in perspective on help-seeking and participation, self-admission may potentially strengthen participants' internal responsibility for their treatment and promote partnership in treatment.
anorexia nervosa; eating disorders; inpatients; patient admissions; patient participation; patient-centered care; voluntary admissions
Very little is known about the prevalence of ADHD symptoms in Bulimia Nervosa and Binge Eating Disorder and even less in other eating disorders. This knowledge gap is of clinical importance since stimulant treatment is proven effective in Binge Eating Disorder and discussed as a treatment possibility for Bulimia Nervosa. The objective of this study was to explore the prevalence and types of self-reported ADHD symptoms in an unselected group of eating disorder patients assessed in a specialized eating disorder clinic.
In total 1165 adults with an eating disorder were assessed with a battery of standardized instruments, for measuring inter alia ADHD screening, demographic variables, eating disorder symptoms and psychiatric comorbidity. Chi-square tests were used for categorical variables and Kruskal-Wallis tests for continuous variables.
Almost one third (31.3 %) of the patients scored above the screening cut off indicating a possible ADHD. The highest prevalence rates (35-37 %) were found in Bulimia Nervosa and Anorexia Nervosa bingeing/purging subtype, while Eating Disorder Not Otherwise Specified type 1-4 and Binge Eating Disorder patients reported slightly below average (26-31 %), and Anorexia Nervosa restricting subtype patients even lower (18 %). Presence of binge eating, purging, loss of control over eating and non-anorectic BMI were related to results indicating a possible ADHD. Psychiatric comorbidity correlated to ADHD symptoms without explaining the differences between eating disorder diagnoses.
There is a high frequency of ADHD symptoms in patients with binge eating/purging eating disorders that motivates further studies, particularly concerning the effects of ADHD medication. The finding that the frequency of ADHD symptoms in anorexia nervosa with binge eating/purging is as high as in bulimia nervosa highlights the need also for this group.
ADHD; Anorexia nervosa; Binge eating disorder; Bulimia nervosa; Comorbidity; Eating disorders; Prevalence; Purging
Prior research based on self-reports has proven sexual abuse to be a risk factor for pain and psychiatric disorders. However, less is known about how this is reflected within the healthcare system. The aim of this study was to study the 2-year prevalence of diagnosis of sexual abuse and concomitant conditions.
Using data from VAL, the study population included all living persons in Stockholm County, Sweden, between 1 January 2008 and 31 December 2014 (N=2 549 496). Diagnoses of sexual abuse were identified during 2013-2014, with information on the concomitant conditions somatic pain, depression, anxiety, psychotic disorders and bipolar disorders, stress disorders and alcohol and substance abuse. All diagnoses were prospectively registered. Age and neighbourhood socioeconomic status-adjusted ORs with 95% CIs for individuals with a diagnosis of sexual abuse, using individuals without sexual abuse as referents, were calculated.
Girls at the ages 13-17 years had the highest 2-year prevalence (0.69%) of sexual abuse followed by girls 5-12 years (0.11%), and girls 0-4 years (0.04%). For women 45 years and older the 2-year prevalence rates were substantially lower (0.008-0.004%). The highest 2-year prevalence of sexual abuse in men was seen in boys 5-12 (0.03%) years. The total 2-year prevalence of diagnoses of sexual abuse among the population in the material was 0.04%. The highest ORs of comorbidities for girls (ages 0-17 years) with sexual abuse versus those without sexual abuse were: Stress disorder; 15.7 (13.1 to 18.9), drug abuse; 10.0 (7.7 to 13.0), and alcohol abuse; 9.7(7.8 to 12.0). For boys (ages 0-17 years), the highest ORs of comorbidities were: Stress disorder 12.4 (6.0 to 25.7), anxiety disorders; 5.5 (2.6 to 11.5), and alcohol abuse; 3.9 (1.4 to 11.3). The highest ORs of comorbidities for women (18-) with sexual abuse versus those without sexual abuse were: alcohol abuse; 19.3 (12.6 to 29.6), drug abuse; 16.7 (10.7 to 26.1) and psychotic disorders; 15.3 (8.0 to 29.4). For men (18-) the highest ORs of comorbidities were: alcohol abuse; 25.8 (15.2 to 43.9), anxiety disorders; 14.3 (8.5 to 24.2) stress disorder; 12.9 (7.5 to 22.1) and drug abuse; 12.9 (6.9 to 24.1).
Diagnoses of drug and alcohol abuse, psychotic, bipolar, stress anxiety disorders, depression and somatic pain are more common among individuals with a diagnosis of sexual abuse than among individuals without a diagnosis of sexual abuse.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
DRUG MISUSE; Epidemiology of chronic non communicable diseases; PRIMARY CARE; PSYCHIATRY; Social and life-course epidemiology
This study investigated the long-term outcomes of internet-delivered cognitive behavior therapy (ICBT) for children with anxiety disorders, and potential pre-treatment predictors of treatment outcome.
The sample included eighty-four children (8-12 years old) with anxiety disorders, from both a treatment group and a waitlist control (after participants had crossed over to treatment) of a previous randomized controlled study. Participants were assessed at post-treatment and three- and twelve-months after treatment using a semi-structured interview and parent ratings. Pre-treatment data were used to investigate predictors of treatment outcome at three-month follow-up.
Intention-to-treat analysis showed that treatment gains were maintained at twelve-month follow-up, including clinician rated severity of the principal anxiety disorder, parent rated anxiety symptoms and global functioning, with mainly large effect sizes (Cohen's d = 0.63-2.35). Completer analyses showed that suspected autism spectrum disorder was associated with less change in symptom severity. No other pre-treatment measures significantly predicted treatment outcome.
This study suggests that internet-delivered CBT can have long-term beneficial effects for children with anxiety disorders. Predictors of treatment outcome need to be evaluated further.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Anxiety disorders; CBT; Children; Internet-delivered treatment
Autism spectrum disorder (ASD) and social anxiety disorder (SAD) have partly overlapping symptoms. Gaze avoidance has been linked to both SAD and ASD, but little is known about differences in social attention between the two conditions. We studied eye movements in a group of treatment-seeking adolescents with SAD (N = 25), assessing SAD and ASD dimensionally. The results indicated a double dissociation between two measures of social attention and the two symptom dimensions. Controlling for social anxiety, elevated autistic traits were associated with delayed orienting to eyes presented among distractors. In contrast, elevated social anxiety levels were associated with faster orienting away from the eyes, when controlling for autistic traits. This distinction deepens our understanding of ASD and SAD.
Attention; Autism spectrum disorder (ASD); Avoidance; Broader autism phenotype; Eye tracking; Gaze avoidance; Orienting; Social anxiety disorder (SAD)
Cognitive-behavioral therapy (CBT) is the first-line treatment for young people with obsessive-compulsive disorder (OCD), but most patients do not have access to this treatment. Thus, innovative ways to increase the accessibility of CBT are needed. The objective of this trial was to evaluate the efficacy of therapist-guided internet-based CBT (ICBT) for adolescents with OCD.
Sixty-seven adolescents (12-17 years old) with OCD were randomly assigned to a 12-week clinician- and parent-supported ICBT program (BiP OCD) or a waitlist condition. The primary outcome was the Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS) administered by blinded assessors before and after the intervention. All patients were followed up 3 months after the intervention.
In intention-to-treat analyses, BiP OCD was superior to waitlist on the CY-BOCS (time-by-group interaction, B = -4.53, z = -3.74, p < .001; Cohen's d = 0.69; 95% CI 0.19-1.18) and on most secondary outcome measurements. Patients randomized to BiP OCD also showed further improvement from post-treatment to 3-month follow-up, with a within-group pretreatment to follow-up effect size (Cohen's d) equal to 1.68 (95% CI 1.00-2.36). Patient satisfaction with BiP OCD was high. There were no relevant adverse events. Average clinician support time was 17.5 minutes per patient per week.
Therapist-guided ICBT is a promising low-intensity intervention for adolescents with OCD and has the potential to increase access to CBT. It might be particularly useful in a stepped-care approach, in which a large proportion of patients with moderately severe OCD could first be offered ICBT, thus freeing limited resources for more complex cases. Clinical trial registration information-Internet-Delivered CBT for Adolescents With OCD: A Randomized Controlled Study (BiPOCD); http://clinicaltrials.gov; NCT02191631.
Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
cognitive-behavioral therapy; internet; obsessive-compulsive disorder
This study tested whether including objects perceived as highly interesting by children with autism during a gaze following task would result in increased first fixation durations on the target objects. It has previously been found that autistic children differentiate less between an object another person attends to and unattended objects in terms of this measure. Less differentiation between attended and unattended objects in ASD as compared to control children was found in a baseline condition, but not in the high interest condition. However, typically developing children differentiated less between attended and unattended objects in the high interest condition than in the baseline condition, possibly reflecting reduced influence of gaze cues on object processing when objects themselves are highly interesting.
Circumscribed interests; Communication; Gaze following; Joint attention; Social cognition
Norepinephrine transporter (NET) in the brain plays important roles in human cognition and the pathophysiology of psychiatric disorders. Two radioligands, (S,S)-11C-MRB and (S,S)-18F-FMeNER-D2, have been used for imaging NETs in the thalamus and midbrain (including locus coeruleus) using PET in humans. However, NET density in the equally important cerebral cortex has not been well quantified because of unfavorable kinetics with (S,S)-11C-MRB and defluorination with (S,S)-18F-FMeNER-D2, which can complicate NET quantification in the cerebral cortex adjacent to the skull containing defluorinated 18F radioactivity. In this study, we have established analysis methods of quantification of NET density in the brain including the cerebral cortex using (S,S)-18F-FMeNER-D2 PET. Methods: We analyzed our previous (S,S)-18F-FMeNER-D2 PET data of 10 healthy volunteers dynamically acquired for 240 min with arterial blood sampling. The effects of defluorination on the NET quantification in the superficial cerebral cortex was evaluated by establishing a time stability of NET density estimations with an arterial input 2-tissue-compartment model, which guided the less-invasive reference tissue model and area under the time-activity curve methods to accurately quantify NET density in all brain regions including the cerebral cortex. Results: Defluorination of (S,S)-18F-FMeNER-D2 became prominent toward the latter half of the 240-min scan. Total distribution volumes in the superficial cerebral cortex increased with the scan duration beyond 120 min. We verified that 90-min dynamic scans provided a sufficient amount of data for quantification of NET density unaffected by defluorination. Reference tissue model binding potential values from the 90-min scan data and area under the time-activity curve ratios of 70- to 90-min data allowed for the accurate quantification of NET density in the cerebral cortex. Conclusion: We have established methods of quantification of NET densities in the brain including the cerebral cortex unaffected by defluorination using (S,S)-18F-FMeNER-D2 These results suggest that we can accurately quantify NET density with a 90-min (S,S)-18F-FMeNER-D2 scan in broad brain areas.
(S,S)-18F-FMeNER-D2; cerebral cortex; norepinephrine transporter; positron emission tomography
This observational study examined user characteristics, intervention use patterns, and variables associated with reductions in alcohol consumption for anonymous Internet help-seekers using a Web-based self-help program.
A Web-based cognitive behavioral therapy (CBT) program with eight modules delivered over 10 weeks was offered to participants with at least hazardous use of alcohol according to the Alcohol Use Disorders Identification Test (AUDIT) (n = 4165). At baseline and 10-week follow-up, participants completed the Timeline-followback (TLFB), AUDIT, Drug Use Disorders Identification Test (DUDIT), Hospital Anxiety and Depression Scale (HADS), EuroQol-5 dimension (EQ-5D), World Health Organization Quality of Life Scale-abbreviated version (WHOQOL-BREF), Readiness to Change Questionnaire (RCQ), and Readiness Ruler. Follow-up completers and non-completers were compared at baseline, and follow-up completer outcomes were reported. Predictors of change in drinking behavior were evaluated at follow-up.
Registered users were 41.88 years old on average (SD = 12.36), and 52 % were women; the mean baseline number of drinks during the past week was 27.27 (SD = 17.92) with 62 % in the AUDIT category of probable dependence and only 7 % having low-risk consumption according to public health guidelines. At follow-up (n = 1043), 53 % showed a clinically significant change to a lower level of alcohol use (χ2 = 254.403, p < 0.001); the mean alcohol consumption fell (t = 22.841, p < 0.001) and the proportion with low-risk consumption rose to 40 %. Being male, scoring higher on baseline readiness, completing the program, and accessing other support predicted low-risk drinking and clinically significant change to a lower level of alcohol use at follow-up.
A publicly available Web-based program for managing problematic alcohol use attracted users with considerable alcohol- and health-related problems, which were changed to lower severity for follow-up completers.
Alcohol; Cognitive behavioral; Harmful drinking; Internet; Substance use disorders; Treatment program; eHealth
Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share inhibitory control deficits possibly underlying poor control over stereotyped and repetitive and compulsive behaviors, respectively. However, it is unclear whether these symptom profiles are mediated by common or distinct neural profiles. This comparative multimodal meta-analysis assessed shared and disorder-specific neuroanatomy and neurofunction of inhibitory functions.
A comparative meta-analysis of 62 voxel-based morphometry and 26 functional magnetic resonance imaging (fMRI) studies of inhibitory control was conducted comparing gray matter volume and activation abnormalities between patients with ASD (structural MRI: 911; fMRI: 188) and OCD (structural MRI: 928; fMRI: 247) and control subjects. Multimodal meta-analysis compared groups across voxel-based morphometry and fMRI.
Both disorders shared reduced function and structure in the rostral and dorsomedial prefrontal cortex including the anterior cingulate. OCD patients had a disorder-specific increase in structure and function of left basal ganglia (BG) and insula relative to control subjects and ASD patients, who had reduced right BG and insula volumes versus OCD patients. In fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal activation and reduced posterior cingulate deactivation, whereas OCD patients showed temporoparietal underactivation.
The multimodal comparative meta-analysis shows shared and disorder-specific abnormalities. Whereas the rostrodorsomedial prefrontal cortex was smaller in structure and function in both disorders, this was concomitant with increased structure and function in BG and insula in OCD patients, but a reduction in ASD patients, presumably reflecting a disorder-specific frontostriatoinsular dysregulation in OCD in the form of poor frontal control over overactive BG, and a frontostriatoinsular maldevelopment in ASD with reduced structure and function in this network. Disorder-differential mechanisms appear to drive overlapping phenotypes of inhibitory control abnormalities in patients with ASD and OCD.
Copyright © 2016. Published by Elsevier Inc.
Autism; Cognitive control; Meta-analysis; OCD; VBM; fMRI
Few treatments have been able to effectively manage pediatric irritable bowel syndrome (IBS). Internet-delivered cognitive behavior therapy (Internet-CBT) based on exposure for abdominal symptoms is effective for adult IBS. The objective of this study was to evaluate the efficacy of Internet-CBT based on behavioral exposure for adolescents with IBS.
Adolescents with IBS fulfilling the Rome III criteria were randomized to either Internet-CBT or a wait-list control. The Internet-CBT was a 10-week intervention where the main component was exposure to IBS symptoms by reduction of avoidance of abdominal symptoms and instead stepwise provocation of symptoms. The primary outcome was total score on Gastrointestinal Symptoms Rating Scale for IBS (GSRS-IBS). Secondary outcomes included adolescent- and parent-rated quality of life and parent-rated gastrointestinal symptoms. Difference between groups was assessed from pretreatment to posttreatment and the Internet-CBT group was also evaluated at 6 months after treatment completion.
A total of 101 adolescents with IBS (13-17 years of age) were included in this study. Dropout rates were low (6%) and all randomized patients were included in intent-to-treat analyses based on mixed effects models. Analyses showed a significant larger pretreatment to posttreatment change on the primary outcome GSRS-IBS (B=-6.42, P=0.006, effect size Cohen's d=0.45, 95% confidence interval (0.12, 0.77)) and on almost all secondary outcomes for the Internet-CBT group compared with the control group. After 6 months, the results were stable or significantly improved.
Internet-CBT based on exposure exercises for adolescents with IBS can effectively improve gastrointestinal symptoms and quality of life.
Persons with neuropsychiatric disorders are at increased risk of suicide, but there is little data concerning Tourette's and chronic tic disorders (TD/CTD). We aimed to quantify the risk of suicidal behavior in a large nationwide cohort of patients with TD/CTD, establish the contribution of psychiatric comorbidity to this risk, and identify predictors of suicide.
Using a validated algorithm, we identified 7736 TD/CTD cases in the Swedish National Patient Register during a 44-year period (1969-2013). Using a matched case-cohort design, patients were compared with general population control subjects (1:10 ratio). Risk of suicidal behavior was estimated using conditional logistic regressions. Predictors of suicidal behavior in the TD/CTD cohort were studied using Cox regression models.
In unadjusted models, TD/CTD patients, compared with control subjects, had an increased risk of both dying by suicide (odds ratio: 4.39; 95% confidence interval [CI]: 2.89-6.67) and attempting suicide (odds ratio: 3.86; 95% CI: 3.50-4.26). After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial. Persistence of tics beyond young adulthood and a previous suicide attempt were the strongest predictors of death by suicide in TD/CTD patients (hazard ratio: 11.39; 95% CI: 3.71-35.02, and hazard ratio: 5.65; 95% CI: 2.21-14.42, respectively).
TD/CTD are associated with substantial risk of suicide. Suicidal behavior should be monitored in these patients, particularly in those with persistent tics, history of suicide attempts, and psychiatric comorbidities. Preventive and intervention strategies aimed to reduce the suicidal risk in this group are warranted.
Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Chronic tic disorder; Premature mortality; Psychiatric epidemiology; Suicide; Suicide attempt; Tourette’s disorder
The Greater Stockholm HIV Cohort Study is an initiative to provide longitudinal information regarding the health of people living with HIV.
Our aim was to explore the prevalence of HIV and its association with psychiatric co-morbidities.
All patients with a recorded diagnosis of HIV (any position of the ICD-10 codes B20-B24) were identified during the period 2007-2014 and related to the total population in Stockholm by January 1, 2015, N = 2.21 million. The age at diagnosis, gender, and first occurrence of an HIV diagnosis was recorded. Analyses were done by age and gender. Prevalence of psychiatric co-morbidities amongst HIV patients were recorded.
Age-adjusted odds ratios with 95% confidence intervals were calculated with logistic regression for prevalent psychiatric co-morbidities in HIV infected individuals compared to the prevalence in the general population.
The total prevalence of HIV was 0.16%; females 0.10% (n = 1134) and males 0.21% (n = 2448). HIV-infected people were more frequently diagnosed with psychiatric illnesses and drug abuse. In females and males with HIV-diagnosis respectively, drug dependence disorder was 7.5 (7.76% vs 1.04%) and 5.1 (10.17% vs 1.98%) times higher, psychotic disorders were 6.3 (2.65% vs 0.42%) and 2.9 (1.43% vs 0.49%) times higher, bipolar disorder was 2.5 (1.41% vs 0.57%) and 3 (1.02% vs 0.34%) times higher, depression diagnosis was 1.5 (8.47% vs 5.82%) and 3.4 (10.17% vs 2.97%) higher, trauma-related disorder was 1.5 (6.00% vs 4.10%) respectively 2.9 (4.45% vs 1.56%) times higher, anxiety disorder was 1.2 (6.88% vs 5.72%) and 2.2 (6.54% vs 2.93%) times higher than in their non-infected peers.
Despite effective ART, many individuals with HIV have an impaired mental health and a history of drug abuse that may threaten the vision of a contained epidemic.
Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Administrative databases; Anxiety disorders; Bipolar disorders; Depression; Drug dependence disorders; Epidemiology; Gender; General population; Psychotic disorders; Trauma-related disorders
The gateway hypothesis posits that initial exposure to legal drugs promotes subsequent addiction to illicit drugs. However, epidemiological studies are correlational and cannot rule out the alternative hypothesis of shared addiction vulnerability to legal and illegal drugs. We tested the gateway hypothesis using established rat alcohol exposure procedures and cocaine self-administration and reinstatement (relapse) procedures. We gave Wistar or alcohol-preferring (P) rats intermittent access to water or 20% alcohol in their homecage for 7 weeks (three 24-h sessions/week). We also exposed Wistar rats to air or intoxicating alcohol levels in vapor chambers for 14-h/day for 7 weeks. We then tested the groups of rats for acquisition of cocaine self-administration using ascending cocaine doses (0.125, 0.25, 0.5, 1.0 mg/kg/infusion) followed by a dose-response curve after acquisition of cocaine self-administration. We then extinguished lever pressing and tested the rats for reinstatement of drug seeking induced by cocaine-paired cues and cocaine priming (0, 2.5, 5, 10 mg/kg, i.p.). Wistar rats consumed moderate amounts of alcohol (4.6 g/kg/24 h), P rats consumed higher amounts of alcohol (7.6 g/kg/24 h), and Wistar rats exposed to alcohol vapor had a mean blood alcohol concentration of 176.2 mg/dl during the last week of alcohol exposure. Alcohol pre-exposure had no effect on cocaine self-administration, extinction responding, and reinstatement of drug seeking. Pre-exposure to moderate, high, or intoxicating levels of alcohol had no effect on cocaine self-administration and relapse to cocaine seeking. Our data do not support the notion that alcohol is a gateway drug to cocaine.
To evaluate associations between binge-eating disorder (BED) and somatic illnesses and determine whether medical comorbidities are more common in individuals who present with BED and comorbid obesity.
Cases (n = 850) were individuals with a BED diagnosis in the Swedish eating disorders quality registers. Ten community controls were matched to each case on sex, and year, month, and county of birth. Associations of BED status with neurologic, immune, respiratory, gastrointestinal, skin, musculoskeletal, genitourinary, circulatory, and endocrine system diseases were evaluated using conditional logistic regression models. We further examined these associations by adjusting for lifetime psychiatric comorbidity. Amongst individuals with BED, we explored whether comorbid obesity was associated with risk of somatic disorders.
BED was associated with most classes of diseases evaluated; strongest associations were with diabetes [odds ratio (95% confidence interval) = 5.7 (3.8; 8.7)] and circulatory systems [1.9 (1.3; 2.7)], likely indexing components of metabolic syndrome. Amongst individuals with BED, those with comorbid obesity were more likely to have a lifetime history of respiratory [1.5 (1.1; 2.1)] and gastrointestinal [2.6 (1.7; 4.1)] diseases than those without comorbid obesity. Increased risk of some somatic disease classes in individuals with BED was not simply due to obesity or other lifetime psychiatric comorbidity.
The association of BED with many somatic illnesses highlights the morbidity experienced by individuals with BED. Clinicians treating patients with BED should be vigilant for medical comorbidities. Nonpsychiatric providers may be the first clinical contact for those with BED underscoring the importance of screening in primary care. © 2016 The Authors International Journal of Eating Disorders Published by Wiley Periodicals, Inc. (Int J Eat Disord 2017; 50:58-65).
© 2016 The Authors International Journal of Eating Disorders Published by Wiley Periodicals, Inc.
binge-eating disorder; cardiovascular; gastrointestinal; medical comorbidity; metabolic syndrome; physical; somatic
Attention-deficit/hyperactivity disorder (ADHD) aggregates in families. To date, the strength, pattern, and characteristics of the familial aggregation have not been thoroughly assessed in a population-based family sample.
In this cohort study, we identified relative pairs of twins, full and half-siblings, and full and half cousins from 1,656,943 unique individuals born in Sweden between 1985 and 2006. The relatives of index persons were followed from their third birthday to 31 December 2009 for ADHD diagnosis. Birth year adjusted hazard ratio (HR), that is, the rate of ADHD in relatives of ADHD-affected index persons compared with the rate of ADHD in relatives of unaffected index persons, was estimated in the different types of relatives using Cox proportional hazards model.
During the follow-up, 31,865 individuals were diagnosed with ADHD (male to female ratio was 3.7). The birth year adjusted HRs were as follows: 70.45 for monozygotic twins; 8.44 for dizygotic twins; 8.27 for full siblings; 2.86 for maternal half-siblings; 2.31 for paternal half-siblings; 2.24 for full cousins; 1.47 for half cousins. Maternal half-siblings had significantly higher HR than in paternal half-siblings. The HR did not seem to be affected by index person's sex. Full siblings of index persons with ADHD diagnosis present at age 18 or older had a higher rate of ADHD (HR: 11.49) than full siblings of index persons with ADHD diagnosis only before age 18 (HR: 4.68).
Familial aggregation of ADHD increases with increasing genetic relatedness. The familial aggregation is driven by not only genetic factors but also a small amount of shared environmental factors. Persistence of ADHD into adulthood indexes stronger familial aggregation of ADHD.
© 2016 Association for Child and Adolescent Mental Health.
Attention-deficit/hyperactivity disorder; adulthood; diagnosis; family factor; sex differences
The risk of death by suicide in individuals with obsessive-compulsive disorder (OCD) is largely unknown. Previous studies have been small and methodologically flawed. We analyzed data from the Swedish national registers to estimate the risk of suicide in OCD and identify the risk and protective factors associated with suicidal behavior in this group. We used a matched case-cohort design to estimate the risk of deaths by suicide and attempted suicide in individuals diagnosed with OCD, compared with matched general population controls (1:10). Cox regression models were used to study predictors of suicidal behavior. We identified 36 788 OCD patients in the Swedish National Patient Register between 1969 and 2013. Of these, 545 had died by suicide and 4297 had attempted suicide. In unadjusted models, individuals with OCD had an increased risk of both dying by suicide (odds ratio (OR)=9.83 (95% confidence interval (CI), 8.72-11.08)) and attempting suicide (OR=5.45 (95% CI, 5.24-5.67)), compared with matched controls. After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial for both death by suicide and attempted suicide. Within the OCD cohort, a previous suicide attempt was the strongest predictor of death by suicide. Having a comorbid personality or substance use disorder also increased the risk of suicide. Being a woman, higher parental education and having a comorbid anxiety disorder were protective factors. We conclude that patients with OCD are at a substantial risk of suicide. Importantly, this risk remains substantial after adjusting for psychiatric comorbidities. Suicide risk should be carefully monitored in patients with OCD.
Early intensive behavioural intervention (EIBI) for children with autism spectrum disorder (ASD) is often delivered using a community model. Behaviour modification experts train and supervise non-experts (e.g. preschool personnel) to teach children according to applied behaviour analysis principles in their natural environment. Several factors predict EIBI outcomes in ASD, for example, knowledge of EIBI and EIBI allegiance among trainers. The aim of the present study was to survey levels of knowledge about and allegiance towards EIBI.
Formal knowledge of EIBI and EIBI allegiance was surveyed in supervised preschool staff conducting EIBI (n = 33), preschool staff not involved in EIBI (n = 26), behaviour modification experts (n = 60), school staff (n = 25) and parents of children with ASD (n = 150) [N = 294]. A 27-item (15 knowledge and 12 allegiance questions) online questionnaire was collected.
Supervised preschool staff conducting EIBI had more knowledge than preschool staff not using EIBI, but they were not more allegiant. Compared with behaviour modification experts, the supervised EIBI preschool staff group showed markedly less knowledge and allegiance.
Findings indicate potential for improvement regarding formal knowledge levels of preschool staff delivering EIBI to children with ASD in real-world settings. In addition, fostering EIBI allegiance might be prioritized when teaching EIBI among non-experts. Broadly increased EIBI knowledge levels among all preschool teachers should be achieved by adding behaviour modification techniques to common university curricula in preschool education. Allegiance of preschool personnel might be accomplished by EIBI supervisors meeting skepticism in practice with conveyance of evidence-based principles and discussions of ethical issues.
© 2016 John Wiley & Sons Australia, Ltd.
behaviour modification; neurodevelopmental disorder; outcomes; therapy; treatment
Construct validity; Gaming addiction; Internet Gaming Disorder; Internet addiction; Psychometrics