Centrum för psykiatriforskning
Norra Stationsgatan 69, plan 7
113 64 Stockholm
Här samlar vi ett antal av de vetenskapliga artiklar som CPF:s forskare publicerar. Listorna baseras på bibliometrisökningar i databasen PubMed och är därför inte fullständiga och kan innehålla fel. Samtliga länkar leder till PubMed.
Self-harm is common and there is a need for studies that investigate the relevance of this behavior in clinical samples to inform risk assessment and treatment. The objectives in the current studies were to compare clinical and psychosocial correlates and subsequent adverse outcomes in youth who present to child and adolescent mental health services (CAMHS) with self-harm only (SH), self-harm with suicidality (SH+SU), with those without any indication of SH or SH+SU.
We conducted a case-control study and a longitudinal cohort study using data from a regional clinical care register, and Swedish national registers. The case-control study included all patients (5-17 years) between 2011 and 2015 (N = 25,161). SH and SH+SU cases were compared with controls (patients without SH) regarding a range of correlates. The longitudinal study included former CAMHS patients (N = 6,120) who were followed for a median time of 2.8 years after termination of CAMHS contact regarding outcomes such as clinical care consumption, social welfare recipiency, and crime conviction.
In the case-control study, both the SH and SH+SU groups received more clinical care, had lower global functioning, and higher odds of having mental disorders compared to controls. In most comparisons, the SH+SU group had more problems than the SH group. In the longitudinal study, the same pattern emerged for most outcomes; for example, the adjusted hazard ratio for recurrent care due to self-harm was 23.1 (95% confidence interval [CI], 17.0-31.4) in the SH+SU group compared to 3.9 (95% CI, 2.3-6.7) in the SH group.
Adolescent patients presenting with self-harm have higher risks for adverse outcomes than patients without self-harm. Suicidality in addition to self-harm is associated with more severe outcomes, importantly recurrent episodes of care for self-harm.
© 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.
Self-harm; cohort study; epidemiology; self-injurious behavior; suicidal ideation
Clinical trials have demonstrated the efficacy of internet delivered cognitive behaviour therapy (ICBT) for anxiety and depression. However, relatively little is known about the context, operations, and outcomes of ICBT when administered as part of routine care. This paper describes the setting, relationship to existing health services, procedures for referral, assessment, treatment, patients and outcomes of ICBT clinics in Sweden, Denmark, Norway, Canada and Australia. All five clinics provide services free or at low cost to patients. All have systems of governance to monitor quality of care, patient safety, therapist performance and data security. All five clinics include initial assessments by clinicians and between 10 and 20 min of therapist support during each week. Published reports of outcomes all demonstrate large clinical improvement, low rates of deterioration, and high levels of patient satisfaction. Services that require a face to face assessment treat smaller numbers of patients and have fewer patients from remote locations. The paper shows that therapist-guided ICBT can be a valuable part of mental health services for anxiety and depression. Important components of successful ICBT services are rigorous governance to maintain a high standard of clinical care, and the measurement and reporting of outcomes.
Anxiety; Delivery; Depression; Description; Disorders; Implementation; Internet-delivered cognitive behaviour therapy; Psychological treatment; Routine care
Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and the most common neurodevelopmental disorder in childhood. In recent decades, it has been appreciated that in a substantial number of cases the disorder does not remit in puberty, but persists into adulthood. Both in childhood and adulthood, ADHD is characterised by substantial comorbidity including substance use, depression, anxiety, and accidents. However, course and symptoms of the disorder and the comorbidities may fluctuate and change over time, and even age of onset in childhood has recently been questioned. Available evidence to date is poor and largely inconsistent with regard to the predictors of persistence versus remittance. Likewise, the development of comorbid disorders cannot be foreseen early on, hampering preventive measures. These facts call for a lifespan perspective on ADHD from childhood to old age. In this selective review, we summarise current knowledge of the long-term course of ADHD, with an emphasis on clinical symptom and cognitive trajectories, treatment effects over the lifespan, and the development of comorbidities. Also, we summarise current knowledge and important unresolved issues on biological factors underlying different ADHD trajectories. We conclude that a severe lack of knowledge on lifespan aspects in ADHD still exists for nearly every aspect reviewed. We encourage large-scale research efforts to overcome those knowledge gaps through appropriately granular longitudinal studies.
Adult-onset ADHD; Cognitive impairment; Comorbidity; Developmental trajectory; Genetics; Treatment
Atopic dermatitis (AD) is a common and debilitating inflammatory dermatological disorder and is marked by itch and inflamed skin. Scratching, sleep loss, and avoidance of situations associated with more AD symptoms are central hypothesized mechanisms that perpetuate the disorder and cause reduced quality of life. We developed an exposure-based cognitive behavioral treatment (CBT) that entailed mindfulness practice as a means to increase tolerance for aversive experiences during exposure. The aim of the present study was to test the treatment's acceptability and preliminary efficacy in adults with AD. We used an uncontrolled pretest-posttest design and recruited participants (N = 9) from a university hospital dermatological clinic. The treatment comprised 10 weekly sessions over 10 weeks and assessments of AD symptoms as well as psychiatric symptoms and quality of life were conducted at baseline, posttreatment and 6-month follow-up. The results showed significant and large baseline to posttreatment improvements on self-reported measures of AD symptoms (p = .020) and general anxiety (p = .005), but there was no significant improvement in depression or quality of life. Treatment satisfaction was high and a majority of participants (67%) completed the treatment. We conclude that exposure-based CBT for adult AD can be feasible, acceptable, and potentially efficacious.
Atopic dermatitis; cognitive behavior therapy; exposure treatment; skin disorder
Expert guidelines recommend cognitive-behavioural therapy (CBT) as a first-line treatment for obsessive-compulsive disorder (OCD), but the majority of patients with OCD do not have access to CBT. Internet-delivered CBT (ICBT) has the potential to make this evidence-based treatment more accessible while requiring less therapist time than traditional face-to-face (f2f) CBT. Data from six clinical trials suggest that ICBT for OCD is both efficacious and cost-effective, but whether ICBT is non-inferior to traditional f2f CBT for OCD is yet unknown.
A single-blind, randomised, controlled, non-inferiority trial comparing therapist-guided ICBT, unguided ICBT and individual (f2f) CBT for adult OCD patients. The primary objective is to investigate whether ICBT is non-inferior to gold standard f2f CBT. Secondary objectives are to investigate if ICBT is equally effective when delivered unguided, to establish the cost-effectiveness of ICBT and to investigate if the treatment outcome differs between self-referred and clinically referred patients. Participants will be recruited at two specialist OCD clinics in Stockholm and also through online self-referral. Participants will be randomised to one of three treatment conditions: F2f CBT, ICBT with therapist support or unguided ICBT. The total number of participants will be 120, and masked assessments will be administered at baseline, biweekly during treatment, at post-treatment and at 3-month and 12-month follow-ups. The main outcome measure is the clinician-rated Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at 3-month follow-up. The margin of non-inferiority is set to 3 points on the Y-BOCS using a 90% CI.
The study has been approved by the Regional Ethics Board of Stockholm (REPN 2015/1099-31/2) and registered at Clinicaltrials.gov (NCT02541968). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
adult psychiatry; clinical randomized controlled trial; internet delivered cognitive behaviour theraphy; non-inferiority study; obsessive compulsive disorder
Research on child-related risk factors for filicide is scant. We investigated whether prior healthcare use for injury (including poisoning) influences filicide risk. Victims (0-14 years; n = 71) were identified in a national autopsy database for the years 1994-2012 and compared to matched, general population controls (n = 355). Healthcare use data were retrieved from a national patient registry. Risks were estimated using odds ratios (ORs) and 95% confidence intervals (CIs). For females, prior inpatient care for injury conferred a statistically significant sevenfold risk (OR = 6.67 [95% CI: 1.49-29.79]), and any prior injury-related healthcare use conferred a statistically significant fourfold risk (OR = 3.57 [95% CI: 1.13-11.25]), of filicide victimization. No statistically significant risks were found for males. Healthcare personnel should be aware that children treated for injuries, especially females, may be at an elevated risk of filicide victimization. Nevertheless, the filicide base rate remains low, and parents may be stigmatized by unfounded alerts; thus, prudent reflection should precede reports to the authorities.
case-control; child homicide; filicide; filicide-suicide; forensic science; healthcare use
Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.
In this nationwide population-based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.
We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal-related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.
The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.
© 2018 Association for Child and Adolescent Mental Health.
anorexia nervosa; autoimmunity; bulimia nervosa; cox regression; hazard; immune system; risk
Maternal infection during pregnancy (IDP) has been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. However, infection is associated with social adversity, poor living conditions and other background familial factors. As such, there is a need to rule out whether the observed association between maternal IDP and ADHD might be attributed to such confounding.
This nationwide population-based cohort study using a family-based, quasi-experimental design included 1,066,956 individuals born in Sweden between 1992 and 2002. Data on maternal IDP (bacterial or viral) requiring hospitalization and ADHD diagnosis in offspring were gathered from Swedish National Registers, with individuals followed up through the end of 2009. Ordinary and stratified Cox regression models were used for estimation of hazard ratios (HRs) and several measured covariates were considered. Cousin- and sibling-comparisons accounted for unmeasured genetic and environmental factors shared by cousins and siblings.
In the entire population, maternal IDP was associated with ADHD in offspring (HR = 2.31, 95% CI = 2.04-2.61). This association was attenuated when accounting for measured covariates (HR = 1.86, 95% CI = 1.65-2.10). The association was further attenuated when adjusting for unmeasured factors shared between cousins (HR = 1.52, 95% CI = 1.12-2.07). Finally, the association was fully attenuated in sibling comparisons (HR = 1.03, 95% CI = 0.76-1.41).
This study suggests that the association between maternal IDP and offspring ADHD is largely due to unmeasured familial confounding. Our results underscore the importance of adjusting for unobserved familial risk factors when exploring risk factors for ADHD.
© 2018 Association for Child and Adolescent Mental Health.
Maternal infection during pregnancy; attention-deficit/hyperactivity disorder; cousin comparisons; familial confounding; quasi-experimental; sibling comparisons
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
Initial internet-based cognitive behavioral therapy (iCBT) programs for anxiety disorders in children and young people (CYP) have been developed and evaluated, however these have not yet been widely adopted in routine practice. The lack of guidance and formalized approaches to the development and dissemination of iCBT has arguably contributed to the difficulty in developing iCBT that is scalable and sustainable beyond academic evaluation and that can ultimately be adopted by healthcare providers. This paper presents a consensus statement and recommendations from a workshop of international experts in CYP anxiety and iCBT (#iCBTLorentz Workshop Group) on the development, evaluation, engagement and dissemination of iCBT for anxiety in CYP.
Adolescents; Anxiety; Children; Cognitive behavioral therapy; Development; Dissemination; Online treatments
To evaluate neurodevelopmental difficulties in children with idiopathic clubfoot.
A cross-sectional study of 106 children (29 females, 77 males; aged 8-10y) with idiopathic clubfoot and 109 age-, sex-, and residential area-parallelized children from the general population. Neurodevelopmental difficulties were assessed using the parent-report Five to Fifteen (FTF) questionnaire. Group differences were analysed for FTF domains, subdomains, and items. The 90th centile cut-off of the general population on FTF and the parent-based disease-specific instrument (DSI) were used to evaluate clinical relevance of neurodevelopmental symptoms in idiopathic clubfoot.
Modest group differences were found for several FTF domains (motor skills, perception, and language) and subdomains (gross and fine motor skills, relation in space, comprehensive and expressive language skills). Thirty-one per cent of the children with idiopathic clubfoot scored in the clinically significant range on 2 or more FTF domains. DSI scores were lower in this subgroup.
Findings indicate a moderate and selective increase of neurodevelopmental difficulties in children with idiopathic clubfoot as a whole, especially in the areas of motor skills, perception, and language. Idiopathic clubfoot with marked neurodevelopmental symptoms are associated with less satisfaction of the clubfoot treatment. Our results recommend awareness of neurodevelopmental difficulties in the assessment and treatment of idiopathic clubfoot.
A substantial minority of children with idiopathic clubfoot show neurodevelopmental difficulties. Children with idiopathic clubfoot might present additional difficulties in motor skills, perception, and language. Children with idiopathic clubfoot and marked neurodevelopmental symptoms show poorer parent-reported clubfoot treatment satisfaction. Neurodevelopmental difficulties should be considered in clinical practice of idiopathic clubfoot.
© 2018 Mac Keith Press.
Accumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients.
CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer.
We found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning.
These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
first-episode psychosis; neuroimmunology; schizophrenia
Evidence-based practice for healthy lifestyle promotion in primary health care is supported internationally by national policies and guidelines but implementation in routine primary health care has been slow. Referral to digital interventions could lead to a larger proportion of patients accessing structured interventions for healthy lifestyle promotion, but such referral might have unknown implications for clinicians with patients accessing such interventions. This qualitative study aimed to explore the perceptions of clinicians in primary care on healthy lifestyle promotion with or without digital screening and intervention.
Focus group interviews were conducted at 10 primary care clinics in Sweden with clinicians from different health professions. Transcribed interviews were analyzed using content analysis, with inspiration from a phenomenological-hermeneutic method involving naïve understanding, structural analysis and comprehensive understanding.
Two major themes captured clinicians' perceptions on healthy lifestyle promotion: 1) the need for structured professional practice and 2) deficient professional practice as a hinder for implementation. Sub-themes in theme 1 were striving towards professionalism, which for participants meant working in a standardized fashion, with replicable routines regardless of clinic, as well as being able to monitor statistics on individual patient and group levels; and embracing the future with critical optimism, meaning expecting to develop professionally but also being concerned about the consequences of integrating digital tools into primary care, particularly regarding the importance of personal interaction between patient and provider. For theme 2, sub-themes were being in an unmanageable situation, meaning not being able to do what is perceived as best for the patient due to lack of time and resources; and following one's perception, meaning working from a gut feeling, which for our participants also meant deviating from clinical routines.
In efforts to increase evidence-based practice and lighten the burden of clinicians in primary care, decision- and policy-makers planning the introduction of digital tools for healthy lifestyle promotion will need to explicitly define their role as complements to face-to-face encounters. Our overriding hope is that this study will contribute to maintaining meaningfulness in the patient-clinician encounter, when digital tools are added to facilitate patient behavior change of unhealthy lifestyle behaviors.
Clinician experiences; Digital interventions; E-health; Healthy lifestyle promotion; Phenomenological hermeneutics; Primary care; Qualitative research
The schizophrenia and bipolar twin study in Sweden (STAR) is a large nation-wide cohort of monozygotic (MZ) and dizygotic (DZ) same-sex twins with schizophrenia or bipolar disorder and healthy control pairs, extensively characterized with brain imaging, neuropsychological tests, biomarkers, genetic testing, psychiatric symptoms and personality traits. The purpose is to investigate genetic and environmental mechanisms that give rise to schizophrenia and bipolar disorder as well as the intermediate phenotypes. This article describes the design, recruitment, data collection, measures, collected twins' characteristics, diagnostic procedures as well as ongoing and planned analyses. Identification of biomarkers, genetic and epigenetic variation and the development of specific and common endophenotypes for schizophrenia and bipolar disorder are potential gains from this cohort.
Biomarker; Endophenotype; Etiology; Gene-environment interaction; Neuroimaging; Psychiatry
The opioid antagonist, naltrexone, has been shown to reduce the risk of relapse in amphetamine dependence, but the mechanisms behind this effect are not well understood. We aimed to investigate if naltrexone attenuates cue reactivity and craving in amphetamine dependence.
Forty men with severe, intravenous amphetamine dependence were randomized to one dose of naltrexone (50 mg) or placebo. In a BOLD fMRI cue reactivity paradigm, they were exposed to drug-related and neutral films and gave subjective ratings of craving after each film. Twenty-nine patients left data of sufficient quality to be included in the final analysis.
The drug-related films elicited strong subjective craving and BOLD activations of the striatum, cingulate cortex, and occipito-temporal visual attention networks. Longer history of amphetamine use was associated with greater activations of the prefrontal cortex. Naltrexone as compared to placebo had no significant effects on brain activations or subjective ratings.
Patients with severe stimulant use disorder exhibit strong neural cue reactivity, the patterns of which are modulated by duration of drug use. In this sample, we found no evidence for any effects of naltrexone on cue reactivity.
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Amphetamine dependence; Functional magnetic resonance imaging; Naltrexone; Stimulant use disorder
Pharmacoepidemiological studies have long raised concerns on widespread use of benzodiazepines and benzodiazepine-related drugs (BZDs), in particular long-term use, among adults and the elderly. In contrast, evidence pertaining to the rates of BZD use at younger ages is still scarce, and the factors that influence BZD utilisation and shape the different prescribing patterns in youths remain largely unexplored. We examined the prevalence rates, relative changes in rates over time, and prescribing patterns for BZD dispensation in young people aged 0-24 years in Sweden during the period January 1, 2006-December 31, 2013, and explored demographic, clinical, pharmacological, and prescriber-related attributes of BZD prescribing in this group.
Through the linkage of 3 nationwide Swedish health and administrative registers, we collected data on 17,500 children (0-11 years), 15,039 adolescents (12-17 years), and 85,200 young adults (18-24 years) with at least 1 dispensed prescription for a BZD during 2006-2013, out of 3,726,818 Swedish inhabitants aged 0-24 years. Age-specific annual prevalence rates of BZD dispensations were adjusted for population growth, and relative changes in rates were calculated between 2006 and 2013. We analysed how BZD dispensation varied by sex, psychiatric morbidity and epilepsy, concurrent dispensation of psychotropic medication, type of dispensed BZD, and type of healthcare provider prescribing the BZD. Prescribing patterns were established in relation to duration (3 months, >3 to ≤6 months, or >6 months), dosage (<0.5 defined daily dosage [DDD]/day, ≥0.5 to <1.5 DDD/day, or ≥1.5 DDD/day), and "user category" ("regular users" [≥0.5 to <1.5 DDD/day for ≥1 year], "heavy users" [≥1.5 DDD/day for ≥1 year], or otherwise "occasional users"). Multinomial regression models were fitted to test associations between BZD prescribing patterns and individual characteristics of study participants. Between 2006 and 2013, the prevalence rate of BZD dispensation among individuals aged 0-24 years increased by 22% from 0.81 per 100 inhabitants to 0.99 per 100 inhabitants. This increase was mainly driven by a rise in the rate among young adults (+20%), with more modest increases in children (+3%) and adolescents (+7%). Within each age category, overall dispensation of BZD anxiolytics and clonazepam decreased over time, while dispensation of BZD hypnotics/sedatives, including Z-drugs, showed an increase between 2006 and 2013. Out of 117,739 study participants with dispensed BZD prescriptions, 65% initiated BZD prescriptions outside of psychiatric services (92% of children, 60% of adolescents, 60% of young adults), and 76% were dispensed other psychotropic drugs concurrently with a BZD (46% of children, 80% of adolescents, 81% of young adults). Nearly 30% of the participants were prescribed a BZD for longer than 6 months (18% of children, 31% of adolescents, 31% of young adults). A high dose prescription (≥1.5 DDD/day) and heavy use were detected in 2.6% and 1.7% of the participants, respectively. After controlling for potential confounding by demographic and clinical characteristics, the characteristics age above 11 years at the first BZD dispensation, lifetime psychiatric diagnosis or epilepsy, and concurrent dispensation of other psychotropic drugs were found to be associated with higher odds of being prescribed a BZD for longer than 6 months, high dose prescription, and heavy use. Male sex was associated with a higher likelihood of high dose prescription and heavy use, but not with being prescribed a BZD on a long-term basis (> 6 months). The study limitations included lack of information on actual consumption of the dispensed BZDs and unavailability of data on the indications for BZD prescriptions.
The overall increase in prevalence rates of BZD dispensations during the study period and the unexpectedly high proportion of individuals who were prescribed a BZD on a long-term basis at a young age indicate a lack of congruence with international and national guidelines. These findings highlight the need for close monitoring of prescribing practices, particularly in non-psychiatric settings, in order to build an evidence base for safe and efficient BZD treatment in young persons.
Psychotherapy can alleviate mental distress and improve quality of life, but little is known about its potential negative effects and how to determine their frequency.
To present a commentary on the current understanding and future research directions of negative effects in psychotherapy.
An anonymous survey was distributed to a select group of researchers, using an analytical framework known as strengths, weaknesses, opportunities and threats.
The researchers perceive an increased awareness of negative effects in psychotherapy in recent years, but also discuss some of the unresolved issues in relation to their definition, assessment and reporting. Qualitative methods and naturalistic designs are regarded as important to pursue, although a number of obstacles to using such methods are identified.
Negative effects of psychotherapy are multifaceted, warranting careful considerations in order for them to be monitored and reported in research settings and routine care.
Negative effects; SWOT; commentary; psychotherapy
Disorder-specific internet-based cognitive-behavioural therapy (ICBT) is effective for depression, panic disorder and social anxiety. In this benchmarking study, a new, individually tailored, ICBT programme (TAIL) showed effects on depression (n = 284, d = 1.33) that were non-inferior to disorder-specific ICBT for depression in routine care (n = 2358, d = 1.35). However, the hypotheses that TAIL for individuals with social anxiety or panic disorder is inferior to disorder-specific ICBT could not be rejected (social anxiety: TAIL d = 0.74 versus disorder-specific d = 0.81; panic: TAIL d = 1.11 versus disorder-specific d= 1.47). Our findings strengthen the empirical base for TAIL as an alternative to disorder-specific ICBT for depression.
cognitive–behavioural therapies; comorbidity; depressive disorders
Ten per cent of all pregnant women are depressed. Standard therapy of pregnant women with moderate depression is selective serotonin reuptakeinhibitors (SSRI). Observational studies on neurodevelopment after fetal SSRI exposure show conflicting results. Our primary objective is to compare the cognitive development in children exposed to sertraline and maternal depression with those exposed to maternal depression and placebo in utero. We hypothesise that there is a significant neurodevelopmental difference between the groups. As a secondary objective, we study the add-on effect of sertraline to internet-based cognitive behavioural therapy (ICBT) to treat moderate depression during pregnancy.
MAGDALENA is a randomised, placebo-controlled, double-blinded trial in Stockholm Healthcare Region with 2.3 million inhabitants. The women are recruited in weeks 9-21 of pregnancy either through Antenatal Health Clinics or through social media. They are to be diagnosed with moderate depression without ongoing antidepressive therapy or any serious comorbidity. The women in the intervention arm receive sertraline combined with a 12-week period of ICBT; the control arm is treated with placebo and ICBT. We assess the cognitive development in the offspring at the age of 2 years using Bayley Scales of Infant and Toddler Development, third edition (BSID-III). We aim at recruiting 200 women, 100 women in each treatment arm, to ensure statistical power to detect a clinically relevant difference between the groups.
This randomised trial will provide long-sought evidence about the effects of SSRI and maternal depression during pregnancy on the neurodevelopment in the offspring. The study is approved by the Regional Ethical Review Board at Karolinska Institutet in Stockholm and the Swedish Medical Products Agency. It is registered with the European Clinical Trials Database (EudraCT), Number: 2013-004444-31. Results will be disseminated at scientific conferences, published in peer-reviewed journals and made available to the public.
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
antenatal depression; drug metabolism; internet-based cognitive behaviour therapy; neurodevelopment; pregnancy; serotonin reuptake inhibitors
Herein, reduced graphene oxide (RGO) has been utilized as an efficient sorbent in microextraction by packed sorbent (MEPS). The combination of MEPS and liquid chromatography-tandem mass spectrometry has been used to develop a method for the extraction and determination of three local anesthetics (i.e. lidocaine, prilocaine, and ropivacaine) in human plasma and saliva samples. The results showed that the utilization of RGO in MEPS could minimize the matrix effect so that no interfering peaks at the retention times of the analytes or internal standard was observed. The high extraction efficiency of this method was approved by mean recoveries of 97.26-106.83% and 95.21-105.83% for the studied analytes in plasma and saliva samples, respectively. Intra- and inter-day accuracies and precisions for all analytes were in good accordance with the international regulations. The accuracy values (as percentage deviation from the nominal value) of the quality control samples were between -2.1 to 13.9 for lidocaine, -4.2 to 11.0 for prilocaine and between -4.5 to -2.4 for ropivacaine in plasma samples while the values were ranged from -4.6 to 1.6 for lidocaine, from -4.2 to 15.5 for prilocaine and from -3.3 to -2.3 for ropivacaine in human saliva samples. Lower and upper limit of quantification (LLOQ, ULOQ) were set at 5 and 2000 nmol L-1 for all of the studied drugs. The correlation coefficients values were ≥0.995. The limit of detection values were obtained 4 nmol L-1 for lidocaine and prilocaine, and 2 nmol L-1 for ropivacaine.
LC-MS/MS; Local anesthetics; Microextraction by packed sorbent; Plasma; Reduced graphene oxide; Saliva
Bipolar disorder carries a high risk of suicide. Identification of risk factors is important. The aim of this study was to study risk factors for suicide in a large cohort of men and women with bipolar disorder.
A prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipoläR). The outcome variable was suicide captured in the Cause of Death Register between 2004 and 2014. Hazard ratios (HR) were calculated using Cox proportional hazards models.
Of 12 850 persons (4844 men and 8006 women) with bipolar disorder, 90 (55 men and 35 women) died by suicide during the follow-up period (between 1 and 10 years). Male sex (HR 2.56), living alone (HR 2.45), previous suicide attempts (HR 4.10), comorbid psychiatric disorder (HR 2.64), recent affective episodes (HR 2.39), criminal conviction (HR 4.43), psychiatric inpatient care (HR 2.79), and involuntary commitment (HR 3.50) were significant risk factors for suicide. Several of the statistically significant risk factors for suicide in bipolar disorder differed between men and women.
Risk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis-specific factors.
© 2018 The Authors. Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.
bipolar disorder; risk factors; suicide
The D1-dopamine receptor radioligand [11C]SCH23390 has been frequently used in PET studies. In drug-naïve patients with schizophrenia, the findings have been inconsistent, with decreases, increases, and no change in the frontal cortex D1-dopamine receptors. While these discrepancies are likely primarily due to a lack of statistical power in these studies, we speculated that an additional explanation may be the differences due to methods of image analysis between studies, affecting reliability as well as bias between groups.
Fifteen healthy subjects underwent two PET measurements with [11C]SCH23390 on the same day. The binding potential (BPND) was compared using a 95% confidence interval following manual and automated delineation of a region of interest (ROI) as well as with and without frame-by-frame realignment.
Automated target region delineation produced lower BPND values, while automated delineation of the reference region yielded higher BPND values. However, no significant differences were observed for repeatability using automated and manual delineation methods. Frame-by-frame realignment generated higher BPND values and improved repeatability.
The results suggest that the choice of ROI delineation method is not an important factor for reliability, whereas the improved results following movement correction confirm its importance in PET image analysis. Realignment is therefore especially important for measurements in patient populations such as schizophrenia or Parkinson's disease, where motion artifacts may be more prevalent.
D1-dopamine receptor; FreeSurfer; Positron emission tomography; ROI; Realignment
Modulation of presynaptic metabotropic glutamate receptor 4 (mGlu4) by an allosteric ligand has been proposed as a promising therapeutic target in Parkinson's disease and levodopa-induced dyskinesia. A positron emission tomography (PET) ligand for an allosteric site of mGlu4 may provide evidence that a clinical drug candidate reaches and binds the target. A carbon-11-labeled PET radioligand binding an allosteric site of mGlu4, [11C]PXT012253, has been recently developed. Here, we describe the detailed characterization of this novel radiolabeled mGlu4 ligand in nonhuman primates.
[11C]PXT012253 binding in the brain of cynomolgus monkeys, under the baseline and blocking conditions with the structurally different mGlu4 allosteric ligand PXT002331, currently in clinical trials for Parkinson's disease, was quantified with compartment and graphical modeling approaches using a radiometabolite-corrected plasma input function. Whole-body biodistribution of [11C]PXT012253 was then assessed using PET/x-ray computed tomography to estimate the human effective doses of [11C]PXT012253 for further clinical studies.
[11C]PXT012253 displayed binding in mGlu4-expressing regions in the brain of cynomolgus monkeys. Brain regional time-activity curves of [11C]PXT012253 were well described in the two-tissue compartment model (2TC). Total distribution volume was stably estimated using Logan plot and multilinear analysis (MA1) although 2TC showed unstable values in some cases. Competition with PXT002331 showed high specific binding in the total distribution volume. Whole-body PET showed high accumulation of [11C]PXT012253 in the liver, kidney, heart, and brain in the initial phase. The radioligand was excreted through both the gastrointestinal and the urinary tracts. Effective dose of [11C]PXT012253 was estimated to be 0.0042 mSv/MBq.
[11C]PXT012253 was shown to be a promising PET radioligand for mGlu4 allosteric modulators in the monkey brain. MA1 would be the choice of quantitative method. Further development of [11C]PXT012253 in human subjects is warranted.
Allosteric; Brain; Dosimetry; Foliglurax; Glutamate; Metabotropic glutamate receptor 4; Positron emission tomography; Primate; Radiotracer
Both internet-based cognitive-behavioural therapy (ICBT) and physical exercise are alternatives to treatment as usual (TAU) in managing mild to moderate depression in primary care.
To determine the cost-effectiveness of ICBT and physical exercise compared with TAU in primary care.
Economic evaluation of a randomised controlled trial (N = 945) in Sweden. Costs were estimated by a service use questionnaire and used together with the effects on quality-adjusted life-years (QALYs). The primary 3-month healthcare provider perspective in primary care was complemented by a 1-year societal perspective.
The primary analysis showed that incremental cost per QALY gain was €8817 for ICBT and €14 571 for physical exercise compared with TAU. At the established willingness-to-pay threshold of €21 536 (£20 000) per QALY, the probability of ICBT being cost-effective is 90%, and for physical exercise is 76%, compared with TAU.
From a primary care perspective, both ICBT and physical exercise for depression are likely to be cost-effective compared with TAU.
Cognitive–behavioural therapies; cost-effectiveness; depressive disorders; exercise; randomised controlled trial
Ample evidence supports the use of Virtual Reality (VR) for anxiety disorders. Nonetheless, currently there is no evidence about moderators or potential negative effects of VR treatment strategies. An Individual Patient Data (IPD) approach was employed with 15 retrieved datasets. The current study sample was composed of 810 patients. Randomized control trials (RCTs) for each primary outcome measure were performed, in addition to moderator analyses of the socio-demographic variables. Deterioration rates were 14 patients (4.0%) in VR, 8 (2.8%) in active control conditions, and 27 (15%) in the WL condition. With regard to receiving treatment, patients in a waiting list control condition had greater odds of deteriorating than in the two active conditions, odds ratios (ORs) 4.87, 95% confidence interval (CI) [0.05, 0.67]. In the case of the socio-demographic variables, none of them were associated with higher or lower odds of deterioration, with the exception of marital status in the WL condition; married people presented a significantly lower probability of deterioration, OR 0.19, 95% CI [0.05, 0.67]. Finally, when comparing pooled effects of VR versus all control conditions, the OR was 0.61 (95% CI 0.31-1.23) in favor of VR, although this result was not statistically significant. This study provides evidence about the deterioration rates of a therapeutic VR approach, showing that the number of deteriorated patients coincides with other therapeutic approaches, and that deterioration is less likely to occur, compared to patients in WL control groups.
Anxiety disorders; Deterioration rates; Individual patient data analysis; Virtual reality
Public speaking anxiety (PSA) is a common condition which can be treated effectively with exposure therapy. However, inherent difficulties in stimuli presentation and control limits dissemination and the therapeutic potential. Virtual Reality (VR) technology has the potential to resolve these issues and provide a scalable platform for self-help interventions. No previous study has examined whether this can be achieved using the first generation of consumer VR hardware and software. In the current trial, n = 25 + 25 participants were randomized to either one-session therapist-led VR exposure therapy for PSA followed by a four-week internet-administered VR to in-vivo transition program, or a waiting-list. Linear mixed effects modeling revealed significant, large (within Cohen's d = 1.67) decreases in self-reported PSA. The waiting-list was then given access to an internet-administered, self-led version of the same VR exposure therapy to be conducted at home, followed by the same transition program. Dual-slope mixed effects modeling revealed significant, large (d = 1.35) decreases in self-reported PSA. Results were maintained or improved at six- and twelve-month follow-ups. We show for the first time that low-cost, off-the-shelf consumer VR hardware and software can be used to conduct exposure therapy for PSA, both in the traditional, previously impractical one-session format, and in a novel self-led, at-home format.
Exposure therapy; In-vivo; Internet interventions; Public speaking anxiety; Social anxiety disorder; Virtual reality
Prolonged exposure to stress can lead to substantial suffering, impairment and societal costs. However, access to psychological treatment is limited. Internet-based cognitive behavioral therapy (ICBT) can be effective in reducing symptoms of stress, but little is known of its effects in clinical samples. The aim of this study was to investigate the efficacy of ICBT for patients suffering from chronic stress, operationalized as adjustment disorder (AD) and exhaustion disorder (ED).
A total of 100 adults diagnosed with AD or ED were randomly assigned to a 12-week ICBT (n = 50) or waitlist control condition (n = 50). Primary outcome was the level of perceived stress (PSS). Secondary outcomes included several mental health symptom domains as well as functional impairment and work ability. All outcomes were assessed at baseline, after treatment and at the 6-month follow-up. The study was preregistered at Clinicaltrials.gov: NCT02540317.
Compared to the control condition, patients in the ICBT group made large and significant improvements on the PSS (d = 1.09) and moderate to large improvements in secondary symptom domains. Effects were maintained at the 6-month follow-up. There was no significant between-group effect on functional impairment or work ability.
A relatively short ICBT is indicated to be effective in reducing stress-related symptoms in a clinical sample of patients with AD and ED, and has the potential to substantially increase treatment accessibility. Results must be replicated, and further research is needed to understand the relationship between symptom reduction, functional impairment and work ability.
© 2018 S. Karger AG, Basel.
Adjustment disorder; Chronic stress; Cognitive behavioral therapy; Exhaustion disorder; Internet; Randomized controlled trial
Emotion dysregulation seems involved in the development, maintenance, and outcome of eating disorders (EDs). The present study aimed to differentiate patients with EDs from a comparison group on emotion dysregulation, and to examine emotion dysregulation in relation to ED diagnostic presentation and ED symptoms.
Participants, patients with EDs (N = 999) and a student comparison group (N = 252), completed the Difficulties in Emotion Regulation Scale and the Eating Disorder Examination Questionnaire. Patients were compared to the comparison group and compared by diagnosis regarding emotion dysregulation, and unique associations between emotion dysregulation aspects and ED symptoms were examined.
Patients reported greater general emotion dysregulation than the comparison group, especially poorer emotional awareness and clarity. There were very few diagnostic differences. In both patients and the comparison group, limited access to emotion regulation strategies was associated with cognitive ED symptoms, and presence of binge eating in the comparison group. In patients, poor emotional awareness and emotional non-acceptance were additionally associated with cognitive symptoms, and difficulties in impulse control and emotional non-acceptance were associated with binge eating.
Emotion dysregulation is an important transdiagnostic characteristic of ED. Results suggest interventions that enhance emotional awareness and acceptance, as well as emotion regulation skills training, in both ED treatment and prevention.
© 2018 Wiley Periodicals, Inc.
Difficulties in Emotion Regulation Scale; eating disorders; emotion dysregulation; emotional awareness; emotional non-acceptance; regulation strategies; transdiagnostic
Evidence syntheses such as systematic reviews and meta-analyses provide a rigorous and transparent knowledge base for translating clinical research into decisions, and thus they represent the basic unit of knowledge in medicine. Umbrella reviews are reviews of previously published systematic reviews or meta-analyses. Therefore, they represent one of the highest levels of evidence synthesis currently available, and are becoming increasingly influential in biomedical literature. However, practical guidance on how to conduct umbrella reviews is relatively limited.
We present a critical educational review of published umbrella reviews, focusing on the essential practical steps required to produce robust umbrella reviews in the medical field.
The current manuscript discusses 10 key points to consider for conducting robust umbrella reviews. The points are: ensure that the umbrella review is really needed, prespecify the protocol, clearly define the variables of interest, estimate a common effect size, report the heterogeneity and potential biases, perform a stratification of the evidence, conduct sensitivity analyses, report transparent results, use appropriate software and acknowledge the limitations. We illustrate these points through recent examples from umbrella reviews and suggest specific practical recommendations.
The current manuscript provides a practical guidance for conducting umbrella reviews in medical areas. Researchers, clinicians and policy makers might use the key points illustrated here to inform the planning, conduction and reporting of umbrella reviews in medicine.
© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.
This observational, cross-sectional, retrospective chart review aimed to identify factors determining health-related quality of life (HRQoL) in adults with newly diagnosed attention-deficit/hyperactivity disorder (ADHD) in Sweden.
Adult participants with a new clinical diagnosis of ADHD were enrolled from two specialist outpatient clinics in Stockholm, Sweden, from 2013 to 2015. Data extracted from patient records included demographics, clinical characteristics and comorbid psychiatric diagnoses identified using the Mini International Neuropsychiatric Interview (MINI). Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale - Self-reported (MADRS-S). The self-rated five-dimension EuroQol questionnaire (EQ-5D) was used to measure HRQoL. Predictors of EQ-5D index score were identified using multivariate linear regression adjusting for age, sex, education level, and main income source.
The mean age of the 189 enrolled patients was 35.2 years (standard deviation [SD], 12.3), and 107 (57%) were female. Psychiatric comorbidities were present in 92 patients (49%), with anxiety and depression being the most common diagnoses. The mean EQ-5D index score was 0.63 (SD, 0.28). Low EQ-5D index scores were significantly associated with high MADRS-S scores, multiple comorbid psychiatric disorders, low educational achievement, female sex, and not having a main income derived from employment or self-employment.
These findings suggest that adults with newly diagnosed ADHD experience low HRQoL, which may often be exacerbated by psychiatric comorbidities such as anxiety and depression. Patients presenting with ADHD and psychiatric comorbidities in adulthood may require particular care and resources in the management of their ADHD.
ADHD; HRQoL; Psychiatric comorbidities
The major transmission route for hepatitis C virus (HCV) is through sharing of unsterile injection equipment among people who inject drugs (PWID). The WHO strategy for HCV elimination by 2030 proposes increased efforts to treat PWID populations that drive the HCV epidemic. Among participants in the Stockholm needle exchange programme (NEP), the HCV prevalence is 60%. We aimed to study HCV incidence, spontaneous HCV clearance rate, and predictors associated with new HCV infections and reinfections in NEP participants. All 2320 patients enrolled in the programme between 8 April 2013 and 23 September 2016 were tested for HCV at baseline, and responded to a questionnaire regarding sociodemographic data and injection risk behaviour. Tests for HCV were repeated at an interval of 3-6 months. The anti-HCV prevalence in the NEP participants at baseline was 77%, and the prevalence of HCV RNA was 57%. 24% of the anti-HCV positive were HCV RNA negative with a spontaneously cleared HCV infection. The overall HCV incidence rate was 22/100 PY. The HCV incidence rate in the HCV naive group was 26/100 PY, and in the spontaneously cleared group 19/100. Although there were no significant differences in becoming HCV infected between the two groups (31% vs 29%), the rate of spontaneous HCV clearance was significantly lower in the HCV naive group, 20% vs 44%, (P < 0.05). A high HCV incidence rate was noted among the PWID indicating that treatment needs to be scaled up in conjunction with harm reduction measures to achieve HCV elimination goals set by WHO. This includes high coverage needle exchange programmes and effective addiction treatment for substance users, including opiate substitution treatment.
PWID; harm reduction; hepatitis C; incidence; needle exchange programmes; reinfection
The purpose was to examine whether sleep hygiene practices are associated with the course of insomnia (incidence, persistence and remission) over 1 year in the general population. This longitudinal study was carried out in the general population. After excluding anyone with other primary sleep disorder than insomnia, 1638 participants returned a baseline and a 1-year follow-up survey. Questions regarding sleep hygiene practices were administered at baseline, and the status of insomnia was assessed at baseline (T1) and at the 1-year follow-up (T2). Age, gender, mental ill-health, and pain were used as covariates in the analyses. Nicotine use, mental ill-health and pain were independently associated with an increased risk for concurrent insomnia at T1, while mental ill-health was the only risk factor for incident insomnia at T2. Relative to not reporting insomnia at the two time-points, nicotine use, light or noise disturbance, mental ill-health, and pain significantly increased the risk for persistent insomnia over 1 year. In comparison with those whose insomnia had remitted at the follow-up, reporting an irregular sleep schedule was a significant risk factor for persistent insomnia. Of the nine sleep hygiene practices examined in this study, only three were independently linked to concurrent and future insomnia, respectively; using nicotine late in the evening, light or noise disturbance, and having an irregular sleep schedule. This may have implications for the conceptualization and management of insomnia as well as for future research.
Epidemiology; Insomnia; Longitudinal; Nicotine; Sleep hygiene; Sleep timing
Internet-delivered cognitive behavioural therapy (ICBT) is a promising approach for increasing access to evidence-based treatments.
To develop and evaluate the feasibility and preliminary efficacy of an ICBT programme for young children with obsessive-compulsive disorder (OCD), named BIP OCD Junior.
Eleven children aged 7-11 years were enrolled in a 12-week open trial of parent- and therapist-guided ICBT for OCD. The primary outcome measure was the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS).
There was a significant improvement in OCD symptoms post-treatment, with a large within-group effect size on the CY-BOCS (Cohen's d = 1.86, 95% CI 0.83 to 2.86). Results were maintained at 3-month follow-up. Both children and parents rated the treatment as credible and were highly satisfied with the intervention.
BIP OCD Junior is a feasible and credible treatment option for young children with OCD. Randomised controlled trials are needed to further establish its efficacy and cost-effectiveness relative to gold standard face-to-face CBT.
Cognitive behavioural therapy; child; early onset; internet-delivered therapy; obsessive-compulsive disorder
The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.
The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.
Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.
The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.
Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Cortical; Imaging; Meta-analysis; Schizophrenia; Surface area; Thickness
Background: Attenuated positive psychotic symptoms represent the defining features of the clinical high-risk for psychosis (CHR-P) criteria. The effectiveness of each available treatment for reducing attenuated positive psychotic symptoms remains undetermined. This network meta-analysis (NMA) investigates the consistency and magnitude of the effects of treatments on attenuated positive psychotic symptoms in CHR-P individuals, weighting the findings for acceptability. Methods: Web of Science (MEDLINE), PsycInfo, CENTRAL and unpublished/gray literature were searched up to July 18, 2017. Randomized controlled trials in CHR-P individuals, comparing at least two interventions and reporting on attenuated positive psychotic symptoms at follow-up were included, following PRISMA guidelines. The primary outcome (efficacy) was level of attenuated positive psychotic symptoms at 6 and 12 months; effect sizes reported as standardized mean difference (SMD) and 95% CIs in mean follow-up scores between two compared interventions. The secondary outcome was treatment acceptability [reported as odds ratio (OR)]. NMAs were conducted for both primary and secondary outcomes. Treatments were cluster-ranked by surface under the cumulative ranking curve values for efficacy and acceptability. Assessments of biases, assumptions, sensitivity analyses and complementary pairwise meta-analyses for the primary outcome were also conducted. Results: Overall, 1,707 patients from 14 studies (57% male, mean age = 20) were included, representing the largest evidence synthesis of the effect of preventive treatments on attenuated positive psychotic symptoms to date. In the NMA for efficacy, ziprasidone + Needs-Based Intervention (NBI) was found to be superior to NBI (SMD = -1.10, 95% CI -2.04 to -0.15), Cognitive Behavioral Therapy-French and Morrison protocol (CBT-F) + NBI (SMD = -1.03, 95% CI -2.05 to -0.01), and risperidone + CBT-F + NBI (SMD = -1.18, 95% CI -2.29 to -0.07) at 6 months. However, these findings did not survive sensitivity analyses. For acceptability, aripiprazole + NBI was significantly more acceptable than olanzapine + NBI (OR = 3.73; 95% CI 1.01 to 13.81) at 12 months only. No further significant NMA effects were observed at 6 or 12 months. The results were not affected by inconsistency or evident small-study effects, but only two studies had an overall low risk of bias. Conclusion: On the basis of the current literature, there is no robust evidence to favor any specific intervention for improving attenuated positive psychotic symptoms in CHR-P individuals.
interventions; network meta-analysis; psychosis; risk; symptoms; treatments
To systematically review the efficacy of psychological, pharmacological, and combined treatments for binge eating disorder (BED).
Systematic search and meta-analysis.
We found 45 unique studies with low/medium risk of bias, and moderate support for the efficacy of cognitive behavior therapy (CBT) and CBT guided self-help (with moderate quality of evidence), and modest support for interpersonal psychotherapy (IPT), selective serotonin reuptake inhibitors (SSRI), and lisdexamfetamine (with low quality of evidence) in the treatment of adults with BED in terms of cessation of or reduction in the frequency of binge eating. The results on weight loss were disappointing. Only lisdexamfetamine showed a very modest effect on weight loss (low quality of evidence). While there is limited support for the long-term effect of psychological treatments, we have currently no data to ascertain the long-term effect of drug treatments. Some undesired side effects are more common in drug treatment compared to placebo, while the side effects of psychological treatments are unknown. Direct comparisons between pharmaceutical and psychological treatments are lacking as well as data to generalize these results to adolescents.
We found moderate support for the efficacy of CBT and guided self-help for the treatment of BED. However, IPT, SSRI, and lisdexamfetamine received only modest support in terms of cessation of or reduction in the frequency of binge eating. The lack of long-term follow-ups is alarming, especially with regard to medication. Long-term follow-ups, standardized assessments including measures of quality of life, and the study of underrepresented populations should be a priority for future research.
Binge eating disorder; Eating disorder; Lisdexamfetamine; Meta-analysis; Psychotherapy; SSRI
Little is known about clinically relevant changes in guided Internet-based interventions for depression. Moreover, methodological and power limitations preclude the identification of patients' groups that may benefit more from these interventions. This study aimed to investigate response rates, remission rates, and their moderators in randomized controlled trials (RCTs) comparing the effect of guided Internet-based interventions for adult depression to control groups using an individual patient data meta-analysis approach. Literature searches in PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from database inception to January 1, 2016. Twenty-four RCTs (4889 participants) comparing a guided Internet-based intervention with a control group contributed data to the analysis. Missing data were multiply imputed. To examine treatment outcome on response and remission, mixed-effects models with participants nested within studies were used. Response and remission rates were calculated using the Reliable Change Index. The intervention group obtained significantly higher response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that older participants (OR = 1.01) and native-born participants (1.66) were more likely to respond to treatment compared to younger participants and ethnic minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the effects of treatment on remission.Moreover, adults with more severe depressive symptoms at baseline were more likely to remit after receiving internet-based treatment (OR = 1.19). Guided Internet-based interventions lead to substantial positive treatment effects on treatment response and remission at post-treatment. Thus, such interventions may complement existing services for depression and potentially reduce the gap between the need and provision of evidence-based treatments.
Depression; Internet-based guided self-help; Meta-analysis; Psychotherapy
Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell hypersensitivity to IR. We report the primary pharmacology of the clinical-grade, exquisitely potent (cell IC50, 0.78 nM), highly selective [>10,000-fold over kinases within the same phosphatidylinositol 3-kinase-related kinase (PIKK) family], orally bioavailable ATM inhibitor AZD1390 specifically optimized for BBB penetration confirmed in cynomolgus monkey brain positron emission tomography (PET) imaging of microdosed 11C-labeled AZD1390 (Kp,uu, 0.33). AZD1390 blocks ATM-dependent DDR pathway activity and combines with radiation to induce G2 cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone. We established a pharmacokinetic-pharmacodynamic-efficacy relationship by correlating free brain concentrations, tumor phospho-ATM/phospho-Rad50 inhibition, apoptotic biomarker (cleaved caspase-3) induction, tumor regression, and survival. On the basis of the data presented here, AZD1390 is now in early clinical development for use as a radiosensitizer in central nervous system malignancies.
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear.
To determine whether there is an association between stress-related disorders and subsequent autoimmune disease.
Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients.
Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions.
Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors.
The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (≥3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at ≤33, 34-41, 42-50, and ≥51 years, respectively; P for interaction < .001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration ≤179, 180-319, and ≥320 days, respectively; P for trend = .03).
In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.
Given the significant impact that psychosocial factors and epilepsy treatments can have on the health-related quality of life (HRQOL) of individuals with epilepsy and their families, there is great clinical interest in the role of psychological evaluation and treatments to improve HRQOL and comorbidities. Therefore, the International League Against Epilepsy (ILAE) charged the Psychology Task Force with the development of recommendations for clinical care based on evaluation of the evidence from their recent Cochrane review of psychological treatments in individuals with epilepsy. The literature search for a recent Cochrane review of randomized controlled trials investigating psychological treatments for individuals with epilepsy constitutes the key source of evidence for this article. To provide practical guidance to service providers, we provide ratings on study research designs based on (1) the American Academy of Neurology's Level of Evidence system and (2) the Grading of Recommendations, Assessment, Development, and Evaluation system. This paper is the culmination of an international collaboration process involving pediatric and adult psychologists, neurologists, psychiatrists, and neuropsychiatrists. The process and conclusions were reviewed and approved by the ILAE Executive Committee. The strongest evidence for psychological interventions was identified for the most common mental health problems, including depression, neurocognitive disturbances, and medication adherence. Psychological interventions targeting the enhancement of HRQOL and adherence and a decrease in comorbidity symptoms (anxiety, depression) should be incorporated into comprehensive epilepsy care. There is a range of psychological strategies (ie, cognitive behavioral therapy and mindfulness-based therapies) that show promise for improving the lives of persons with epilepsy, and clinical recommendations are provided to assist epilepsy health care providers in treating the comorbidities and challenges associated with epilepsy and its treatments.
anxiety; depression; nonpharmacological seizure management; psychoeducation; screening; stigma
Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (α-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood-brain barrier permeability in nonhuman primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate α-syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analogue 14, were then radiolabeled with 11C ( t1/2 = 20.4 min) at high radiochemical purity (>99%) and high specific radioactivity (>37 GBq/μmol). Following intravenous injection of each compound in NHP, a 4-fold higher radioactivity in brain was observed for [11C]14 compared to [11C]12 (0.8 vs 0.2 SUV, respectively). [11C]14 was rapidly eliminated from plasma, with [11C]12 as the major metabolic product observed by radio-HPLC. The presented prodrug approach paves the way for future development of 2-pyridones as imaging biomarkers for in vivo imaging of α-synuclein deposits in brain.
Alpha-synuclein; PET; carbon-11
Recent reports suggest that the mortality gap between persons with schizophrenia and the general population is increasing. We investigated the mortality, age at death, and causes of death among persons diagnosed with schizophrenia and the general population in Finland during 1984-2014.
All persons with schizophrenia in Finland were identified from hospital discharge register, and compared with the Finnish population aged 16 years and older during 1984-2014, based on data from Statistics Finland. Age at death and standardized mortality ratio (SMR) were calculated for each follow-up year.
Mean age at death increased from 57.6 years in 1984 to 70.1 years in 2014 in persons with schizophrenia, and from 70.9 to 77.5 years in the general population. All-cause SMR remained stable during the follow-up (2.6 in 1984 and 2.7 in 2014). A major change was observed in SMR for suicides which decreased from 11.0 in 1984 to 6.6 in 2014 (-40%). The SMRs for cardiovascular and cancer deaths showed increasing trends.
The longevity of persons with schizophrenia is improving at approximately the same rate as the general population but suicide rates have declined substantially. However, there is still a major disparity in mortality compared with general population.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
death; mortality; schizophrenia; suicide
Recent treatment studies with cognitive behavioural therapy for insomnia (CBT-I) have demonstrated effects on both sleep problems and depression. Two previous studies have indicated that the beneficial effect from CBT-I on depression may come through improved sleep, although insomnia severity during treatment had not previously been investigated as a mediator.
Our aim was to investigate if insomnia severity during treatment mediated between CBT-I and depression severity after treatment, in a sample with co-morbid insomnia and depressive symptomology. We also examined whether depressive severity during treatment mediated between CBT-I and insomnia after treatment.
The participants were recruited from advertisements and fulfilled criteria for insomnia diagnosis, and had depressive symptomatology (Beck Depression Inventory-second edition: BDI-II > 13). Two-thirds of the participants were diagnosed with major depressive disorder. The participants received four biweekly group sessions of CBT-I or relaxation training (active control). Insomnia severity (Insomnia Severity Index) and depressive severity (BDI-II) were measured at baseline, mid-treatment, post-treatment and 6-month follow-up. The mid-treatment measures were used as mediators.
Mediational analyses demonstrated a significant reciprocal relationship between insomnia severity and depressive severity throughout CBT-I, although mid-treatment insomnia had a stronger effect on depression than mid-treatment depression had on insomnia. The results were similar for both post-treatment and follow-up.
Some improvement in depressive severity after CBT-I is explained by improved sleep. The findings emphasize the importance of making comorbid insomnia a treatment focus in its own right.
cognitive behavioural therapy; depression; group psychotherapy; insomnia; randomized controlled trial; statistical mediation
Mentalisation-based treatment (MBT) in borderline personality disorder (BPD) has a growing evidence base, but there is a lack of effectiveness and moderator studies. The present study examined the effectiveness of MBT in a naturalistic setting and explored psychiatric and psychological moderators of outcome.
Borderline and general psychiatric symptoms, suicidality, self-harm, alexithymia and self-image were measured in a group of BPD patients (n = 75) receiving MBT; assessments were made at baseline, and subsequently after 6, 12 and 18 months (when treatment ended). Borderline symptoms were the primary outcome variable.
Borderline symptoms improved significantly (d = 0.79, p < .001), as did general psychiatric symptoms, suicidality, self-harm, self-rated alexithymia and self-image. BPD severity or psychological moderators had no effect on outcome. Younger patients improved more on self-harm, although this could be explained by the fact that older patients had considerably lower baseline self-harm.
MBT seems to be an effective treatment in a naturalistic setting for BPD patients. This study is one of the first studies of MBT showing that outcomes related to mentalisation, self-image and self-rated alexithymia improved. Initial symptom severity did not influence results indicating that MBT treatment is well adapted to patients with severe BPD symptoms.
The study was retrospectively registered 25 September 2017 in the ClinicalTrials.gov PRS registry, no. NCT03295838 .
Alexithymia; Borderline personality disorder; Mentalization-based treatment; Pragmatic clinical trials as topic; Psychotherapy; Treatment outcome
Since the beginning of the twenty-first century, there has been an increased focus on developing and testing cognitive components and therapies for insomnia disorder. The aim of the current review was thus to describe and review the efficacy of cognitive components and therapies for insomnia. A systematic review was conducted on 32 studies (N = 1455 subjects) identified through database searches. Criteria for inclusion required that each study constituted a report of outcome from a cognitive component or therapy, that the study had a group protocol, adult participants with diagnosed insomnia or undiagnosed insomnia symptoms or reported poor sleep, and that the study was published until and including 2016 in English. Each study was systematically reviewed with a standard coding sheet. Several cognitive components, a multi-component cognitive program, and cognitive therapy were identified. It is concluded that there is support for paradoxical intention and cognitive therapy. There are also other cognitive interventions that appears promising, such as cognitive refocusing and behavioral experiments. For most interventions, the study quality was rated as low to moderate. We conclude that several cognitive treatment components and therapies can be viewed as efficacious or promising interventions for patients with insomnia disorder. Methodologically stronger studies are, however, warranted.
CBT; Cognitive therapy; Efficacy; Insomnia; Systematic review
Preventing psychosis in patients at clinical high risk may be a promising avenue for pre-emptively ameliorating outcomes of the most severe psychiatric disorder. However, information on how each preventive intervention fares against other currently available treatment options remains unavailable. The aim of the current study was to quantify the consistency and magnitude of effects of specific preventive interventions for psychosis, comparing different treatments in a network meta-analysis. PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, and unpublished/grey literature were searched up to July 18, 2017, to identify randomized controlled trials conducted in individuals at clinical high risk for psychosis, comparing different types of intervention and reporting transition to psychosis. Two reviewers independently extracted data. Data were synthesized using network meta-analyses. The primary outcome was transition to psychosis at different time points and the secondary outcome was treatment acceptability (dropout due to any cause). Effect sizes were reported as odds ratios and 95% confidence intervals (CIs). Sixteen studies (2,035 patients, 57% male, mean age 20.1 years) reported on risk of transition. The treatments tested were needs-based interventions (NBI); omega-3 + NBI; ziprasidone + NBI; olanzapine + NBI; aripiprazole + NBI; integrated psychological interventions; family therapy + NBI; D-serine + NBI; cognitive behavioural therapy, French & Morrison protocol (CBT-F) + NBI; CBT-F + risperidone + NBI; and cognitive behavioural therapy, van der Gaag protocol (CBT-V) + CBT-F + NBI. The network meta-analysis showed no evidence of significantly superior efficacy of any one intervention over the others at 6 and 12 months (insufficient data were available after 12 months). Similarly, there was no evidence for intervention differences in acceptability at either time point. Tests for inconsistency were non-significant and sensitivity analyses controlling for different clustering of interventions and biases did not materially affect the interpretation of the results. In summary, this study indicates that, to date, there is no evidence that any specific intervention is particularly effective over the others in preventing transition to psychosis. Further experimental research is needed.
Psychosis; antipsychotics; cognitive behavioural therapy; family therapy; guidelines; integrated psychological interventions; needs-based interventions; network meta-analysis; omega-3; prevention; risk
Metals are critical to neurodevelopment, and dysregulation in early life has been documented in autism spectrum disorder (ASD). However, underlying mechanisms and biochemical assays to distinguish ASD cases from controls remain elusive. In a nationwide study of twins in Sweden, we tested whether zinc-copper cycles, which regulate metal metabolism, are disrupted in ASD. Using novel tooth-matrix biomarkers that provide direct measures of fetal elemental uptake, we developed a predictive model to distinguish participants who would be diagnosed with ASD in childhood from those who did not develop the disorder. We replicated our findings in three independent studies in the United States and the UK. We show that three quantifiable characteristics of fetal and postnatal zinc-copper rhythmicity are altered in ASD: the average duration of zinc-copper cycles, regularity with which the cycles recur, and the number of complex features within a cycle. In all independent study sets and in the pooled analysis, zinc-copper rhythmicity was disrupted in ASD cases. In contrast to controls, in ASD cases, the cycle duration was shorter (F = 52.25, P < 0.001), regularity was reduced (F = 47.99, P < 0.001), and complexity diminished (F = 57.30, P < 0.001). With two distinct classification models that used metal rhythmicity data, we achieved 90% accuracy in classifying cases and controls, with sensitivity to ASD diagnosis ranging from 85 to 100% and specificity ranging from 90 to 100%. These findings suggest that altered zinc-copper rhythmicity precedes the emergence of ASD, and quantitative biochemical measures of metal rhythmicity distinguish ASD cases from controls.
To assess the association between benzodiazepine and related drug (BZDR) use and risk of Alzheimer's disease (AD) with cumulative consumption and duration of use based models.
A nationwide nested case-control study of all Finnish community-dwelling persons who received clinically verified AD diagnosis in 2005-2011 (N = 70 719) and their matched controls (N = 282 862). AD diagnosis was based on DSM-IV and NINCDS-ADRDA criteria. BZDR purchases were extracted from the Prescription Register since 1995. The association between BZDR use and AD was assessed using conditional logistic regression with 5-year lag time between exposure and outcome.
Benzodiazepine and related drug use was associated with modestly increased risk of AD (adjusted OR 1.06, 95% CI 1.04-1.08). A dose-response relationship was observed with both cumulative consumption and duration. Adjustment for other psychotropics removed the cumulative dose-response relationship by attenuating the ORs in the highest dose category.
Benzodiazepine and related drug use in general was associated with modestly increased risk of AD. No major differences were observed between different subcategories of BZDRs (i.e. benzodiazepines, Z drugs, short-/medium-acting or long-acting BZDRs). As dose-response relationship abolished after adjustment for other psychotropics, it is possible that the association may partially be due to antidepressants and/or antipsychotics, or concomitant use of these medications.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Alzheimer; dementia; pharmacoepidemiology; risk factors
Capturing functional information is crucial in childhood disability. The International Classification of Functioning, Disability and Health (ICF) Core Sets promote assessments of functional abilities and disabilities in clinical practice regarding circumscribed diagnoses. However, the specificity of ICF Core Sets for childhood-onset disabilities has been doubted. This study aimed to identify content commonalities and differences among the ICF Core Sets for cerebral palsy (CP), and the newly developed Core Sets for autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD).
The categories within each Core Set were aggregated at the ICF component and chapter levels. Content comparison was conducted using descriptive analyses.
The activities and participation component of the ICF was the most covered across all Core Sets. Main differences included representation of ICF components and coverage of ICF chapters within each component. CP included all ICF components, while ADHD and ASD predominantly focused on activities and participation. Environmental factors were highly represented in the ADHD Core Sets (40.5%) compared to the ASD (28%) and CP (27%) Core Sets.
International Classification of Functioning, Disability and Health Core Sets for CP, ASD, and ADHD capture both common but also unique functional information, showing the importance of creating condition-specific, ICF-based tools to build functional profiles of individuals with childhood-onset disabilities.
The International Classification of Functioning, Disability and Health (ICF) Core Sets for cerebral palsy (CP), autism spectrum disorder (ASD), and attention-deficit-hyperactivity disorder (ADHD) include unique functional information. The ICF-based tools for CP, ASD, and ADHD differ in terms of representation and coverage of ICF components and ICF chapters. Representation of environmental factors uniquely influences functioning and disability across ICF Core Sets for CP, ASD and ADHD.
© 2018 Mac Keith Press.
The influence of Tourette syndrome and chronic tic disorders on academic performance has not been objectively quantified.
To investigate the association of Tourette syndrome and chronic tic disorders with objectively measured educational outcomes, adjusting for measured covariates and unmeasured factors shared between siblings and taking common psychiatric comorbidities into account.
A population-based birth cohort consisting of all individuals born in Sweden from 1976 to 1998 was followed up until December 2013. Individuals with organic brain disorders, mental retardation, and 2 foreign-born parents were excluded. We further identified families with at least 2 singleton full siblings and families with siblings discordant for Tourette syndrome or chronic tic disorders.
Previously validated International Classification of Diseases diagnoses of Tourette syndrome or chronic tic disorders in the Swedish National Patient Register.
Eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, and finishing a university degree.
Of the 2 115 554 individuals in the cohort, 3590 had registered a diagnosis of Tourette syndrome or a chronic tic disorder in specialist care (of whom 2822 [78.6%] were male; median [interquartile] age at first diagnosis, 14.0 [11-18] years). Of 726 198 families with at least 2 singleton full siblings, 2697 included siblings discordant for these disorders. Compared with unexposed individuals, people with Tourette syndrome or chronic tic disorders were significantly less likely to pass all core and additional courses at the end of compulsory school (odds ratios ranging from 0.23 [95% CI, 0.20-0.26] for the handcraft textile/wood course to 0.36 [95% CI, 0.31-0.41] for the English language course) and to access a vocational program (adjusted OR [aOR], 0.31; 95% CI, 0.28-0.34) or academic program (aOR, 0.43; 95% CI, 0.39-0.47) in upper secondary education. Individuals with the disorders were also less likely to finish upper secondary education (aOR, 0.35; 95% CI, 0.32-0.37), start a university degree (aOR, 0.41; 95% CI, 0.37-0.46), and finish a university degree (aOR, 0.39; 95% CI, 0.32-0.48). The results were only marginally attenuated in the fully adjusted sibling comparison models. Exclusion of patients with neuropsychiatric comorbidities, particularly attention-deficit/hyperactivity disorder and pervasive developmental disorders, resulted in attenuated estimates, but patients with Tourette syndrome or chronic tic disorders were still significantly impaired across all outcomes.
Help-seeking individuals with Tourette syndrome or chronic tic disorders seen in specialist settings experience substantial academic underachievement across all educational levels, spanning from compulsory school to university, even after accounting for multiple confounding factors and psychiatric comorbidities.
Some patients with eating disorders (EDs) seem to experience their illness as an entity, a symbolic other to whom they relate, and which may influence both symptom levels and self-image. Extending previous research, this study investigated whether the patient-ED relationship has attachment qualities.
Structural Analysis of Social Behaviour was used to operationalize the patient-ED relationship, and the Attachment Style Questionnaire was used to measure attachment.
We examined ED patients' (N = 148) relationship with their ED, attachment behaviour, symptoms, and self-image. Attachment dimensions of Confidence, Anxious/ambivalence, and Avoidance were found to be significantly correlated with aspects of the patient-ED relationship. Introjection (i.e., whether ED actions were incorporated into patients' self-image) was investigated by examining the match between self-image profiles and the actions of patients' EDs. A double mediation model was tested in which ED control/emancipation and patients' Self-blame mediated the effect of attachment security on ED symptoms.
Attachment insecurity was associated with greater ED control and patient submission. In 28.5% of patients, there was a high degree of correlation between self-image and ED action profile. Data supported the mediation model.
Attachment processes appear to be associated with the manner in which ED patients relate to their disorder, at least in some cases. Attempts to maintain psychological proximity to the ED as an introjected attachment figure may help to explain treatment resistance and ambivalence about change. This perspective may be useful in treatment.
Attachment behaviours are associated with the patient-ED relationship, in which attachment insecurity is correlated with greater eating disorder control and patient submission. Some patients seem to incorporate the actions of the ED in their self-image, suggesting the presence of introjection. The patient-ED relationship may help explain patients' anxiety and ambivalence about change, seen from an attachment perspective. In treatment, it may be important to explore alternative safe havens and secure bases to the ED, such as interpersonal relationships and activities.
© 2018 The British Psychological Society.
attachment behaviors; eating disorders; introjection; self-image; the patient-eating disorder relationship
Air pollution has been widely associated with respiratory diseases. Nevertheless, the association between air pollution and exacerbations of bronchiectasis has been less studied.
To analyze the effect of air pollution on exacerbations of bronchiectasis.
This was a retrospective observational study conducted in Badalona. The number of daily hospital admissions and emergency room visits related to exacerbation of bronchiectasis (ICD-9 code 494.1) between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, SO2, NO2, CO, and PM10 levels on bronchiectasis-related emergencies and hospitalizations on the same day and 1-4 days after. All p values were corrected for multiple comparisons.
SO2 was significantly associated with an increase in the number of hospitalizations (lags 0, 1, 2, and 3). None of these associations remained significant after correcting for multiple comparisons. The number of emergency room visits was associated with higher levels of SO2 (lags 0-4). After correcting for multiple comparisons, the association between emergency room visits and SO2 levels was statistically significant for lag 0 (p = 0.043), lag 1 (p = 0.018), and lag 3 (p = 0.050).
The number of emergency room visits for exacerbation of bronchiectasis is associated with higher levels of SO2.
© 2018 S. Karger AG, Basel.
Air pollution; Bronchiectasis; Exacerbation; SO2; Sulfur dioxide
Social skills group training (SSGT) is widely used for intellectually able children and adolescents with autism spectrum disorder (ASD). Previous studies indicate small to moderate effects on social communication capacities. The duration of most available programs is relatively short, and extended training might lead to further improvement. This randomized controlled trial compared an extended 24-week version of the SSGT program KONTAKT with standard care. The weekly sessions gradually shifted in content from acquisition of new skills to real-world application of the acquired skills. A total of 50 participants with ASD (15 females; 35 males) aged 8-17 years were included. The study was conducted at two child and adolescent psychiatry outpatient units in Sweden. The primary outcome was the Social Responsiveness Scale-Second Edition (SRS-2) rated 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 at 3-months follow-up. Parent-rated SRS-2 scores indicated large effects posttreatment [- 19.2; 95% CI - 29.9 to - 8.5; p < .001, effect size (ES) = 0.76], which were maintained at follow-up (- 20.7; 95% CI - 31.7 to - 9.7; p < .0001, ES = 0.82). These estimates indicate substantially larger improvement than previously reported for shorter SSGT. However, the effects on teacher-rated SRS-2 and most secondary outcomes did not reach statistical significance. Our results suggest added benefits of extended SSGT training, implying that service providers might reach better results by optimizing the delivery of SSGT.
Autism; Group training; Long-term; Neurodevelopmental disorder; Social skills
Many emergency primary health care workers experience aggressive behaviour from patients or visitors. Simple incident-reporting procedures exist for inpatient, psychiatric care, but a similar and simple incident-report for other health care settings is lacking. The aim was to adjust a pre-existing form for reporting aggressive incidents in a psychiatric inpatient setting to the emergency primary health care settings. We also wanted to assess the validity of the severity scores in emergency primary health care.
The Staff Observation Scale - Revised (SOAS-R) was adjusted to create a pilot version of the Staff Observation Scale - Revised Emergency (SOAS-RE). A Visual Analogue Scale (VAS) was added to the form to judge the severity of the incident. Data for validation of the pilot version of SOAS-RE were collected from ten casualty clinics in Norway during 12 months. Variance analysis was used to test gender and age differences. Linear regression analysis was performed to evaluate the relative impact that each of the five SOAS-RE columns had on the VAS score. The association between SOAS-RE severity score and VAS severity score was calculated by the Pearson correlation coefficient.
The SOAS-R was adjusted to emergency primary health care, refined and called The Staff Observation Aggression Scale - Revised Emergency (SOAS-RE). A total of 350 SOAS-RE forms were collected from the casualty clinics, but due to missing data, 291 forms were included in the analysis. SOAS-RE scores ranged from 1 to 22. The mean total severity score of SOAS-RE was 10.0 (standard deviation (SD) =4.1) and the mean VAS score was 45.4 (SD = 26.7). We found a significant correlation of 0.45 between the SOAS-RE total severity scores and the VAS severity ratings. The linear regression analysis showed that individually each of the categories, which described the incident, had a low impact on the VAS score.
The SOAS-RE seems to be a useful instrument for research, incident-recording and management of incidents in emergency primary care. The moderate correlation between SOAS-RE severity score and the VAS severity score shows that application of both the severity ratings is valuable to follow-up of workers affected by workplace violence.
Aggression; Primary health care; Workplace violence
Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9-10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
Callous-unemotional (CU) traits (e.g., lack of empathy, lack of guilt, shallow affect) are associated with severe and persistent conduct problems in youth. There is evidence showing a substantial genetic correlation between CU traits and conduct problems. The etiological associations between CU traits and other psychopathological symptoms, including symptoms of hyperactivity and emotional problems (such as anxiety and depression symptoms), have been less explored. To examine the etiological associations between CU traits and symptoms of conduct problems, hyperactivity and emotional problems separately through the use of a twin design. Participants were same-sex twin pairs (n = 426 twins; 42% female; 43% MZ; age = 15) drawn from the Child and Adolescents Twin Study in Sweden, a longitudinal study of twins born in Sweden. The sample was mainly composed of children who screenpositive on neurodevelopmental problems/mental health problems or at-risk children (i.e., screen-negative children considered to be genetically at-risk siblings). We used self-report measures of CU traits, conduct problems, hyperactivity and emotional problems. Model-fitting analyses were conducted using structural equation modeling. We found a strong positive genetic correlation between CU traits and conduct problems and a moderate genetic correlation between CU traits and hyperactivity. We also found a relatively modest, but significant negative genetic correlation between CU traits and emotional problems. Using a sample of adolescent twins screened for neurodevelopmental problems, we replicated previous findings that showed a strong genetic correlation between CU traits and conduct problems and we extended research by examining further the etiological associations between CU traits and symptoms of hyperactivity and emotional problems.
Callous-unemotional traits; Conduct problems; Emotional problems; Hyperactivity; Twin study
To explore the influence of self-reported Attention Deficit Hyperactivity Disorder (ADHD) symptoms on recovery rate at 1-year follow-up in an unselected group of patients in a specialized eating disorder (ED) clinic.
Four hundred forty-three adult females with an ED were assessed with the ADHD Self-Report Scale for Adults (ASRS-screener), and for demographic variables and ED symptoms. Recovery was registered at 1-year follow-up.
A high degree of ADHD symptoms at baseline was predictive for nonrecovery of ED at 1-year follow-up in patients with loss of control over eating, bingeing, or purging. The presence of inattentive ADHD symptoms was stronger associated with nonrecovery than hyperactive/impulsive symptoms.
A high degree of ADHD symptoms may have a negative impact on recovery in ED. Screening/diagnostic evaluation of ADHD in all loss of control over eating/bingeing/purging ED patients and studies of the effect of implementing ADHD-treatment strategies in this patient group are recommended.
Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.
ADHD; bulimia nervosa; eating disorders; outcome; treatment
The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity.
Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12-18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups.
Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects.
The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity.
Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ADHD; Computational modeling; Disorder specificity; OCD; Reward; fMRI
The second to fourth digit (2D:4D) ratio is of interest in autism spectrum disorder (ASD). Studies on the relationship of this ratio with other neurodevelopmental disorders (NDDs) are lacking. Investigating the association between the ratio and NDDs in twins can provide insight into genetic and/or environmental factors driving the ratio. Hand images were collected in N = 238 twins with NDDs or typical development from 70 monozygotic and 49 dizygotic pairs to examine ratios and their associations to DSM-5 defined categorical NDDs, autistic traits, zygosity, and sex. There were small associations for males between the ratios and any NDD and ADHD diagnoses. Males had lower ratios than females. Future studies exploring the ratio alongside physical anomalies could provide etiological insight into NDDs.
2D:4D ratio; ADHD; Autism; Hormones; Neurodevelopmental disorders; Sex; Twins
The aim of the study was to explore the psychometric properties of the Inventory of Interpersonal Problems (IIP-64) and to compare levels of interpersonal distress in Swedish female outpatients with anorexia nervosa or bulimia nervosa with age- and gender-matched controls.
Totally, 401 participants were included; anorexia nervosa (n = 74), bulimia nervosa (n = 85) and controls (n = 242). All participants completed the IIP-64. The eating disorder (ED) patients also filled out the Eating Disorder Inventory-2/3 (EDI).
Internal consistency of IIP-64 was acceptable to high. Principal component analyses with varimax rotation of the IIP-64 subscales confirmed the circumplex structure with two underlying orthogonal dimensions; affiliation and dominance. Significant correlations between EDI-3 composite scales ineffectiveness and interpersonal problems and IIP-64 were found. ED patients reported higher levels of interpersonal distress than controls on all but one subscale (intrusive/needy).
IIP-64 can be considered to have acceptable to good reliability and validity in a Swedish ED sample. IIP-64 can be a useful complement in assessment of interpersonal problems in ED.
Anorexia nervosa; IIP-64; bulimia nervosa; inventory of interpersonal problems; psychometrics
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.
Job demands, job control and social support have been associated with depressive symptoms. However, it is unknown how these work characteristics are associated with different trajectories of depressive symptoms, which this study aimed to examine.
We included 6679 subjects in the Swedish Longitudinal Occupational Survey of Health (SLOSH), who completed biennial questionnaires in 2006-2016. Group-based trajectory models identified groups with similar development of depressive symptoms. Multinomial logistic regression estimated associations between baseline demands, control, social support and trajectories of depressive symptoms.
We identified six depression trajectories with varying severity and stability across four measurements. High job demands and low social support, but not low control, were associated with higher probability of belonging to subsequent trajectories with higher symptom level compared to very low symptom level. Adjusted risk ratios ranged from 1.26, 95% CI = 1.06-1.51 (low symptom trajectory) to 2.51, 95% CI = 1.43-4.41 (persistent severe symptom trajectory). Results also indicated that onset of high demands, low control and low social support increases depressive symptoms over time.
The results were based on self-reported data and all individuals did not have complete data in all waves.
The results indicated that especially perceptions of high job demands and low social support are associated with higher or increasing levels of depressive symptoms over time. This support the supposition that high job demands, and low social support may have long-term consequences for depressive symptoms and that interventions targeting job demands and social support may contribute to a more favourable course of depression.
Copyright © 2018 Elsevier B.V. All rights reserved.
EU-AIMS is the largest European research program aiming to identify stratification biomarkers and novel interventions for autism spectrum disorder (ASD). Within the program, the Longitudinal European Autism Project (LEAP) has recruited and comprehensively phenotyped a rare sample of 76 monozygotic and dizygotic twins, discordant, or concordant for ASD plus 30 typically developing twins. The aim of this letter is to complete previous descriptions of the LEAP case-control sample, clinically characterize, and investigate the suitability of the sample for ASD twin-control analyses purposes and share some 'lessons learnt.' Among the twins, a diagnosis of ASD is associated with increased symptom levels of ADHD, higher rates of intellectual disability, and lower family income. For the future, we conclude that the LEAP twin cohort offers multiple options for analyses of genetic and shared and non-shared environmental factors to generate new hypotheses for the larger cohort of LEAP singletons, but particularly cross-validate and refine evidence from it.
ADHD; Autism spectrum disorder; Biomarkers; Brain; Cognition; Europe; Genetics; Intervention; Twins
When the primary goal of exercise is to compensate for food intake and to alter body shape and weight, it is considered compulsive and may be harmful. Compulsive exercise (CE) is important in the pathogenesis of eating disorders (EDs). Many healthy adolescents engage in CE too, and this may indicate a risk for EDs. Our aim was to learn more about ED risk factors tied to CE and to try to isolate questions to ask in order to probe for high ED risk in adolescents engaging in CE. Using two well-established instruments (the Structural Analysis of Social Behavior and the Eating Disorders Examination Questionnaire), we studied associations between ED variables and CE in healthy adolescent boys and girls. We examined gender-specific items to generate the best possible fit for each gender. Individuals with CE displayed significantly greater ED pathology and more self-criticism, and this pattern was stronger in girls than in boys. Risk factors for ED among individuals with CE differed slightly for boys and girls. We put forward a set of gender-specific questions that may be helpful when probing for ED risk among adolescents engaging in CE.
compulsive exercise; eating disorder risk; healthy adolescents
Numerous functional magnetic resonance imaging (fMRI) studies have reported sex differences. To empirically evaluate for evidence of excessive significance bias in this literature, we searched for published fMRI studies of human brain to evaluate sex differences, regardless of the topic investigated, in Medline and Scopus over 10 years. We analyzed the prevalence of conclusions in favor of sex differences and the correlation between study sample sizes and number of significant foci identified. In the absence of bias, larger studies (better powered) should identify a larger number of significant foci. Across 179 papers, median sample size was n = 32 (interquartile range 23-47.5). A median of 5 foci related to sex differences were reported (interquartile range, 2-9.5). Few articles (n = 2) had titles focused on no differences or on similarities (n = 3) between sexes. Overall, 158 papers (88%) reached "positive" conclusions in their abstract and presented some foci related to sex differences. There was no statistically significant relationship between sample size and the number of foci (-0.048% increase for every 10 participants, p = 0.63). The extremely high prevalence of "positive" results and the lack of the expected relationship between sample size and the number of discovered foci reflect probable reporting bias and excess significance bias in this literature.
To investigate the risk of psychiatric disorders among children of parents with cancer in a nationwide population-based setting.
Based on Swedish national registers, the study included 101 339 children with parental cancer diagnosed either during pregnancy (N = 1047) or after birth (N = 100 292) that were born during 1983 to 2000. For each exposed child, we randomly selected 10 unexposed children from the general population after individual matching by year of birth and sex. The matched cohort was followed during 2001 to 2010. Clinical diagnoses of psychiatric disorders and use of prescribed psychiatric medications were identified for all children. Cox regression and logistic regression were used to evaluate the associations of parental cancer with psychiatric disorder diagnosis and psychiatric medication use, respectively.
Parental cancer during pregnancy was not associated with the risk of psychiatric disorders overall, although paternal cancer during pregnancy was associated with a higher risk of psychiatric medication use among females. Parental cancer after birth was associated with higher risks of psychiatric disorder diagnoses, particularly stress reaction and adjustment disorders (males: hazard ratio [HR]: 1.24, 95% confidence interval [CI], 1.08-1.43; females: HR: 1.27, 95% CI, 1.14-1.41), and use of psychiatric medication (males: odds ratio [OR]: 1.09, 95% CI, 1.04-1.13; females: OR: 1.14, 95% CI, 1.10-1.18). The positive associations were stronger for parental cancer with poor expected survival and for parental death after cancer diagnosis.
Parental cancer, primarily the life-threatening cancer, might confer a higher risk of psychiatric disorders among children. These findings have potential implications for health care professionals in providing targeted support to children living with a parent with cancer.
Copyright © 2018 John Wiley & Sons, Ltd.
cancer; child of impaired parents; cohort study; mental disorders; oncology
Electroconvulsive therapy (ECT) is used to treat postpartum depression and psychosis based on clinical experience and small observational studies.
The primary aim was to test the hypothesis that the response rate to ECT for depression and psychosis is higher during the postpartum period than outside this period. The secondary aim was to identify predictors of a response to ECT during the postpartum period.
Cases with postpartum depression and/or psychosis received ECT within 6 months of delivery. A matched comparison group with depression and/or psychosis (not within the postpartum period) was identified from the Swedish National Quality Register for ECT. The improvement 1 week after ECT was classified according to the Clinical Global Impressions Scale - Improvement scale (CGI-I) as responder (CGI-I score 1-2) or non-responder (CGI-I score 3-7).
185 cases and 185 comparison group subjects were included (46% with psychosis in each groups). More cases (87.0%) than comparison group subjects (73.5%) responded to ECT (p = 0.001). Adjusted binary regression analysis revealed that more severe symptoms prior to treatment were the only statistically significant predictor of response.
There was no control group without ECT treatment.
The response rate of those with postpartum depression and/or psychosis to ECT was high. The response rate of patients with psychosis or depression was higher during the postpartum period than outside it. This study supports the use of ECT for severe forms of postpartum depression and/or psychosis.
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Electroconvulsive therapy treatment outcome; Postpartum depression; Postpartum psychosis; Puerperal disorders
Responding to one's own name (RtN) has been reported as atypical in children with developmental disorders, yet comparative studies on RtN across syndromes are rare.
We aim to (a) overview the literature on RtN in different developmental disorders during the first 24 months of life, and (b) report comparative data on RtN across syndromes.
In Part 1, a literature search, focusing on RtN in children during the first 24 months of life with developmental disorders, identified 23 relevant studies. In Part 2, RtN was assessed utilizing retrospective video analysis for infants later diagnosed with ASD, RTT, or FXS, and typically developing peers.
Given a variety of methodologies and instruments applied to assess RtN, 21/23 studies identified RtN as atypical in infants with a developmental disorder. We observed four different developmental trajectories of RtN in ASD, RTT, PSV, and FXS from 9 to 24 months of age. Between-group differences became more distinctive with age.
RtN may be a potential parameter of interest in a comprehensive early detection model characterising age-specific neurofunctional biomarkers associated with specific disorders, and contribute to early identification.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Autism spectrum disorder; Cross-syndrome comparison; Developmental disorders; Early identification; Reaction to name; Response to name
Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in the brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined whether patients with first-episode psychosis and schizophrenia had altered TSPO levels compared with healthy control subjects.
PubMed was searched for studies comparing patients with psychosis with healthy control subjects using second-generation TSPO radioligands. The outcome measure was total distribution volume (VT), an index of TSPO levels, in frontal cortex, temporal cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative support for higher, lower, or no difference in patients' TSPO levels compared with healthy control subjects.
Five studies, with 75 participants with first-episode psychosis or schizophrenia and 77 healthy control subjects, were included. BFs showed strong support for lower VT in patients relative to no difference (all BFs > 32), or relative to higher VT (all BFs > 422), in all brain regions. From the posterior distributions, mean patient-control differences in standardized VT values were -0.48 for frontal cortex (95% credible interval [CredInt] = -0.88 to 0.09), -0.47 for temporal cortex (CredInt = -0.87 to -0.07), and -0.63 for hippocampus (CredInt = -1.00 to -0.25).
The lower levels of TSPO observed in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment.
Copyright © 2018 Society of Biological Psychiatry. All rights reserved.
Immune activation; Meta-analysis; Microglia; Positron emission tomography; Psychosis; Schizophrenia; Translocator protein
The aim of this study was to investigate the associations between a series of empirically known risk and protective factors and suicidality among trans people in Sweden.
Participants were self-selected anonymously to a web-based survey conducted in 2014. Univariable and multivariable logistic regression analyses were performed to assess associations between contributing factors and suicide ideation in the past 12 months and lifetime suicide attempts.
The analysis included 796 trans individuals, between 15 and 94 years of age, who live in Sweden. A total of 37% of respondents reported that they have seriously considered suicide during the past 12 months and 32% had ever attempted a suicide. Offensive treatment during the past three months and lifetime exposure to trans-related violence were significantly associated with suicidality. Less satisfaction with contacts with friends and acquaintances and with one's own psychological wellbeing were associated with suicide ideation in the past 12 months. Lack of practical support was associated with lifetime suicide attempts.
Our findings show that suicidality is directly correlated with trans-related victimization. Preventing targeted victimization is, therefore, a key preventive intervention against this elevated suicidality.
life satisfaction; suicide; transgender; victimization
Symptoms of depression, anxiety, and distress are more common in undergraduates compared to age-matched peers. Mental ill health among students is associated with impaired academic achievement, worse occupational preparedness, and lower future occupational performance. Research on mental health promoting and mental ill health preventing interventions has shown promising short-term effects, though the sustainability of intervention benefits deserve closer attention. We aimed to identify, appraise and summarize existing data from randomized control trials (RCTs) reporting on whether the effects of mental health promoting and mental ill health preventing interventions were sustained at least three months post-intervention, and to analyze how the effects vary for different outcomes in relation to follow-up length. Further, we aimed to assess whether the effect sustainability varied by intervention type, study-level determinants and of participant characteristics.
A systematic search in MEDLINE, PsycInfo, ERIC, and Scopus was performed for RCTs published in 1995-2015 reporting an assessment of mental ill health and positive mental health outcomes for, at least, three months of post-intervention follow-up. Random-effect modeling was utilized for quantitative synthesis of the existing evidence with standardized mean difference (Hedges' g) used to estimate an aggregated effect size. Sustainability of the effects of interventions was analyzed separately for 3-6 months, 7-12 months, and 13-18 months of post-intervention follow-up.
About 26 studies were eligible after reviewing 6,571 citations. The pooled effects were mainly small, but significant for several categories of outcomes. Thus, for the combined mental ill health outcomes, symptom-reduction sustained up to 7-12 months post-intervention (standardized mean difference (Hedges' g) effect size (ES) = -0.28 (95% CI [-0.49, -0.08])). Further, sustainability of symptom-reductions were evident for depression with intervention effect lasting up to 13-18 months (ES = -0.30 (95% CI [-0.51, -0.08])), for anxiety up to 7-12 months (ES = -0.27 (95% CI [-0.54, -0.01])), and for stress up to 3-6 months (ES = -0.30 (95% CI [-0.58, -0.03])). The effects of interventions to enhance positive mental health were sustained up to 3-6 months for the combined positive mental health outcomes (ES = 0.32 (95% CI [0.05, 0.59])). For enhanced active coping, sustainability up to 3-6 months was observed with a medium and significant effect (ES = 0.75 (95% CI [0.19, 1.30])).
The evidence suggests long-term effect sustainability for mental ill health preventive interventions, especially for interventions to reduce the symptoms of depression and symptoms of anxiety. Interventions to promote positive mental health offer promising, but shorter-lasting effects. Future research should focus on mental health organizational interventions to examine their potential for students in tertiary education.
Implementation; Intervention; Mental ill health; Positive mental health; Promotion and prevention; Randomized controlled trials; Students in tertiary education; Sustainability; Systematic review and meta-analysis; Whole university approach
Biomarkers; Cerebrospinal fluid; Demyelination; Schizophrenia; Sphingolipids
Severe health anxiety (hypochondriasis), or illness anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, is characterized by preoccupation with fear of suffering from a serious illness in spite of medical reassurance. It is a debilitating, prevalent disorder associated with increased health care utilization. Still, there is a lack of easily accessible specialized treatment for severe health anxiety.
The aims of this paper were to (1) describe the development and setup of a new internet-delivered acceptance and commitment therapy (iACT) program for patients with severe health anxiety using self-referral and a video-based assessment; and (2) examine the feasibility and potential clinical efficacy of iACT for severe health anxiety.
Self-referred patients (N=15) with severe health anxiety were diagnostically assessed by a video-based interview. They received 7 sessions of clinician-supported iACT comprising self-help texts, video clips, audio files, and worksheets over 12 weeks. Self-report questionnaires were obtained at baseline, post-treatment, and at 3-month follow-up. The primary outcome was Whiteley-7 Index (WI-7) measuring health anxiety severity. Depressive symptoms, health-related quality of life (HRQoL), life satisfaction, and psychological flexibility were also assessed. A within-group design was employed. Means, standard deviations, and effect sizes using the standardized response mean (SRM) were estimated. Post-treatment interviews were conducted to evaluate the patient experience of the usability and acceptability of the treatment setup and program.
The self-referral and video-based assessments were well received. Most patients (12/15, 80%) completed the treatment, and only 1 (1/15, 7%) dropped out. Post-treatment (14/15, 93%) and 3-month follow-up (12/15, 80%) data were available for almost all patients. Paired t tests showed significant improvements on all outcome measures both at post-treatment and 3-month follow-up, except on one physical component subscale of HRQoL. Health anxiety symptoms decreased with 33.9 points at 3-month follow-up (95% CI 13.6-54.3, t11= 3.66, P=.004) with a large within-group effect size of 1.06 as measured by the SRM.
Treatment adherence and potential efficacy suggest that iACT may be a feasible treatment for health anxiety. The uncontrolled design and small sample size of the study limited the robustness of the findings. Therefore, the findings should be replicated in a randomized controlled trial. Potentially, iACT may increase availability and accessibility of specialized treatment for health anxiety.
Danish Data Protection Agency, Central Denmark Region: 1-16-02-427-14; https://www.rm.dk/sundhed/faginfo/forskning/datatilsynet/ (Archived by Webcite at http://www.webcitation.org/6yDA7WovM).
©Ditte Hoffmann, Charlotte Ulrikka Rask, Erik Hedman-Lagerlöf, Brjánn Ljótsson, Lisbeth Frostholm. Originally published in JMIR Mental Health (http://mental.jmir.org), 06.04.2018.
acceptance and commitment therapy; behavior therapy; feasibility; health anxiety; hypochondriasis; illness anxiety disorder; internet intervention
The metabotropic glutamate receptor 5 (mGluR5) is a target for drug development and for imaging studies of the glutamate system in neurological and psychiatric disorders. [11C]AZD9272 is a selective mGluR5 PET radioligand that is structurally different from hitherto applied mGluR5 radioligands. In the present investigation we compared the binding patterns of radiolabeled AZD9272 and other mGluR5 radioligands in the non-human primate (NHP) brain. PET studies were undertaken using [11C]AZD9272 and the commonly applied mGluR5 radioligand [11C]ABP688. Autoradiography studies were performed in vitro using [3H]AZD9272 and the standard mGluR5 radioligands [3H]M-MTEP and [3H]ABP688 in NHP tissue. Competition binding studies were undertaken in vivo and in vitro using different mGluR5 selective compounds as inhibitors. In comparison to other mGluR5 radioligands radiolabeled AZD9272 displayed a distinct regional distribution pattern with high binding in ventral striatum, midbrain, thalamus and cerebellum. While the binding of [11C]AZD9272 was almost completely inhibited by the structurally unique mGluR5 compound fenobam (2.0 mg/kg; 98% occupancy), it was only partially inhibited (46% and 20%, respectively) by the mGluR5 selective compounds ABP688 and MTEP, at a dose (2.0 mg/kg) expected to saturate the mGluR5. Autoradiography studies using [3H]AZD9272 confirmed a distinct pharmacologic profile characterized by preferential sensitivity to fenobam. The distinctive binding in ventral striato-pallido-thalamic circuits and shared pharmacologic profile with the pro-psychotic compound fenobam warrants further examination of [11C]AZD9272 for potential application in psychiatric neuroimaging studies.
AZD9272; Autoradiography; Fenobam; Metabotropic glutamate receptor 5; Negative allosteric modulator; PET imaging
This project studies the effect of group-based Acceptance and Commitment Therapy (ACT) following Attention Bias Modification (ABM) on residual symptoms in recurrent depression. ACT is a cognitive-behavioral intervention combining acceptance and mindfulness processes with commitment and behavior-change processes. ACT enjoys modest empirical support in treating depression and has also shown promising results in secondary prevention of depression. The experimental cognitive bias modification (ABM) procedure has been shown to reduce surrogate markers of depression vulnerability in patients in remission from depression. The aim of the current project is to investigate if the effect of group-based ACT on reducing residual depressive symptoms can be enhanced by preceding it with ABM. Also, assessment of the relationship between conceptually relevant therapeutic processes and outcome will be investigated.
An invitation to participate in this project was extended to 120 individuals within a larger sample who had just completed a separate randomized, multisite, clinical trial (referred to hereafter as Phase 1) in which they received either ABM (n = 60) or a control condition without bias modification (n = 60). This larger Phase-1 sample consisted of 220 persons with a history of at least two episodes of major depression who were currently in remission or not fulfilling the criteria of major depression. After its inclusion, Phase-1 participants from the Sørlandet site (n = 120) were also recruited for this study in which they received an 8-week group-based ACT intervention. Measures will be taken immediately after Phase 1, 1 month, 2 months, 6 months, and 1 year after the conclusion of Phase 1.
This study sequentially combines acceptable, nondrug interventions from neuropsychology and cognitive-behavioral psychology in treating residual symptoms in depression. The results will provide information about the effectiveness of treatment and on mechanisms and processes of change that may be valuable in understanding and further developing ABM and ACT, combined and alone.
ClinicalTrials.gov, Identifier: NCT02648165 . Registered on 6 January 2016.
ABM; ACT; Depression
The purpose of this study was to explore the viewpoints of parents of young people with Autism Spectrum Disorder (ASD) in relation to their child's transition to adulthood.
Data were collected during four structured focus groups with 19 parents of young people with ASD with average to high intellectual capacities. Condensed meaning units were identified and checked during focus groups, and were subsequently linked to the International Classification of Functioning, Disability and Health (ICF).
Three major themes emerged: to be understood, to understand the world and to succeed. The ICF domains of activity and participation and environmental factors emerged as having the greatest potential to influence transition outcomes.
Policies and services should focus on strengths to maximise participation in higher education, employment and independent living amongst young people with ASD. Interventions targeting environmental factors could be effective in improving participation in adult life. Person-centred and individualised approaches could further complement this approach supporting the transition to adulthood for people with ASD, ultimately improving outcomes in adulthood.
Early speech-language development of individuals with Rett syndrome (RTT) has been repeatedly characterised by a co-occurrence of apparently typical and atypical vocalisations.
To describe specific features of this intermittent character of typical versus atypical early RTT-associated vocalisations by combining auditory Gestalt perception and acoustic vocalisation analysis.
We extracted N = 363 (pre-)linguistic vocalisations from home video recordings of an infant later diagnosed with RTT. In a listening experiment, all vocalisations were assessed for (a)typicality by five experts on early human development. Listeners' auditory concepts of (a)typicality were investigated in context of a comprehensive set of acoustic time-, spectral- and/or energy-related higher-order features extracted from the vocalisations.
More than half of the vocalisations were rated as 'atypical' by at least one listener. Atypicality was mainly related to the auditory attribute 'timbre', and to prosodic, spectral, and voice quality features in the acoustic domain.
Knowledge gained in our study shall contribute to the generation of an objective model of early vocalisation atypicality. Such a model might be used for increasing caregivers' and healthcare professionals' sensitivity to identify atypical vocalisation patterns, or even for a probabilistic approach to automatically detect RTT based on early vocalisations.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Acoustic vocalisation analysis; Auditory perception; Early vocalisations; Preserved speech variant; Rett syndrome; Speech-language pathology
Patients with obsessive-compulsive disorder (OCD) experience aversive emotions in response to obsessions, motivating avoidance and compulsive behaviors. However, there is considerable ambiguity regarding the brain circuitry involved in emotional processing in OCD, especially whether activation is altered in the amygdala.
We conducted a systematic literature review and performed a meta-analysis-seed-based d mapping-of 25 whole-brain neuroimaging studies (including 571 patients and 564 healthy control subjects) using functional magnetic resonance imaging or positron emission tomography, comparing brain activation of patients with OCD and healthy control subjects during presentation of emotionally valenced versus neutral stimuli. Meta-regressions were employed to investigate possible moderators.
Patients with OCD, compared with healthy control subjects, showed increased activation in the bilateral amygdala, right putamen, orbitofrontal cortex extending into the anterior cingulate and ventromedial prefrontal cortex, and middle temporal and left inferior occipital cortices during emotional processing. Right amygdala hyperactivation was most pronounced in unmedicated patients. Symptom severity was related to increased activation in the orbitofrontal and anterior cingulate cortices and precuneus. Greater comorbidity with mood and anxiety disorders was associated with higher activation in the right amygdala, putamen, and insula as well as with lower activation in the left amygdala and right ventromedial prefrontal cortex.
Patients with OCD show increased emotional processing-related activation in limbic, frontal, and temporal regions. Previous mixed evidence regarding the role of the amygdala in OCD has likely been influenced by patient characteristics (such as medication status) and low statistical power.
Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Comorbidity; Emotion; Emotional interference; Medication; Meta-analysis; Symptom provocation
Major depressive disorder (MDD) is the leading cause of disability worldwide. The serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory receptors such as the serotonin 1B receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the receptor. The last extensive review of 5-HT1BR in the pathophysiology of depression was published 2009, and based mainly on findings from animal studies. Since then, selective radioligands for in vivo quantification of brain 5-HT1BR binding with positron emission tomography has been developed, providing new knowledge on the role of 5-HT1BR in MDD and its treatment. The main focus of this review is the role of 5-HT1BR in relation to MDD and its treatment, although studies of 5-HT1BR in obsessive-compulsive disorder, alcohol dependence, and cocaine dependence are also reviewed. The evidence outlined range from animal models of disease, effects of 5-HT1B receptor agonists and antagonists, case-control studies of 5-HT1B receptor binding postmortem and in vivo, with positron emission tomography, to clinical studies of 5-HT1B receptor effects of established treatments for MDD. Low 5-HT1BR binding in limbic regions has been found in MDD patients. When 5-HT1BR ligands are administered to animals, 5-HT1BR agonists most consistently display antidepressant-like properties, though it is not yet clear how 5-HT1BR is best approached for optimal MDD treatment.
5-HT1B receptors; Antidepressants; Depression; Serotonin
Associations between dopamine receptor levels and pro- and antisocial behavior have previously been demonstrated in human subjects using positron emission tomography (PET) and self-rated measures of personality traits. So far, only one study has focused on the dopamine D1-receptor (D1-R), finding a positive correlation with the trait social desirability, which is characterized by low dominant and high affiliative behavior, while physical aggression showed a negative correlation. The aim of the present study was to replicate these previous findings using a new independent sample of subjects.
Twenty-six healthy males were examined with the radioligand [11C]SCH-23390, and completed the Swedish universities Scales of Personality (SSP) which includes measures of social desirability and physical trait aggression. The simplified reference tissue model with cerebellum as reference region was used to calculate BPND values in the whole striatum and limbic striatum. The two regions were selected since they showed strong association between D1-R availability and personality scores in the previous study. Pearson's correlation coefficients and replication Bayes factors were then employed to assess the replicability and robustness of previous results.
There were no significant correlations (all p values > 0.3) between regional BPND values and personality scale scores. Replication Bayes factors showed strong to moderate evidence in favor no relationship between D1-receptor availability and social desirability (striatum BF01 = 12.4; limbic striatum BF01 = 7.2) or physical aggression scale scores (limbic striatum BF01 = 3.3), compared to the original correlations.
We could not replicate the previous findings of associations between D1-R availability and either pro- or antisocial behavior as measured using the SSP. Rather, there was evidence in favor of failed replications of associations between BPND and scale scores. Potential reasons for these results are restrictive variance in both PET and personality outcomes due to high sample homogeneity, or that the previous findings were false positives.
Alcohol is associated with violent behavior, although little is known regarding to what extent alcohol increases homicide risk. We aimed to estimate risks of homicide offending and victimization conferred by the presence of ethanol in blood by using toxicological data from homicide victims and offenders and from controls who had died in vehicle-related accidents.
From nationwide governmental registries and databases, forensic-toxicological results were retrieved for victims (n = 200) and offenders (n = 105) of homicides committed during the years 2007-2009 and individuals killed in vehicle-related accidents (n = 1629) during the years 2006-2014. Ethanol levels in blood exceeding 0.01 g/100 ml were considered positive.
Using logistic regression, we found that the presence of ethanol in blood conferred a significantly increased risk of homicide offending (age-adjusted odds ratio [aOR] = 3.6, 95% confidence interval [95% CI] = 2.3-5.6) and homicide victimization (aOR = 2.1, 95% CI = 1.4-3.0). After stratification by sex, risk estimates in females were about 3-fold greater than in males for both homicide offending ([aOR = 11.0, 95% CI = 2.4-49.8] versus [aOR = 3.1, 95% CI = 1.9-4.9]) and victimization ([aOR = 5.4, 95% CI = 2.4-12.2] versus [aOR = 1.7, 95% CI = 1.1-2.8]). Sensitivity analyses yielded similar estimates.
The results of the present study are consistent with prior findings suggesting alcohol to be an important risk factor for homicide offending and victimization. Surprisingly, however, associations were more pronounced in females, although additional studies that control for potential confounders are warranted to facilitate speculations about causality.
Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Alcohol; Ethanol; Forensic toxicology; Homicide
In typical development, infants often alternate their gaze between their interaction partners and interesting stimuli, increasing the probability of joint attention toward surrounding objects and creating opportunities for communication and learning. Children with Autism Spectrum Disorder (ASD) have been found to engage less in behaviors that can initiate joint attention compared to typically developing children, but the role of such atypicalities in the development of ASD during infancy is not fully understood. Here, using eye tracking technology in a live setting, we show that 10-month-olds at high familial risk for ASD engage less in alternating gaze during interaction with an adult compared to low risk infants. These differences could not be explained by low general social preference or slow visual disengagement, as the groups performed similarly in these respects. We also found that less alternating gaze at 10 months was associated with more social ASD symptoms and less showing and pointing at 18 months. These relations were similar in both the high risk and the low risk groups, and remained when controlling for general social preference and disengagement latencies. This study shows that atypicalities in alternating gaze in infants at high risk for ASD emerge already during the first 10 months of life - a finding with theoretical as well as potential practical implications.
Autism; Communication; Eye tracking; Infant siblings; Joint attention; Motivation
The dopamine (DA) system is considered to be centrally involved in the pathophysiology of several major psychiatric disorders. Using positron emission tomography (PET), aberrations in dopamine D2/D3-receptors (D2-R) levels and uptake of the DA precursor FDOPA have been shown for schizophrenia, substance abuse and depression. Radioligands for the dopamine D1-receptor (D1-R) have been available for more than three decades, however this receptor subtype has received much less attention in psychiatry research. Here, studies investigating D1-R in psychiatric patients in comparison to healthy control subjects are summarized. Although small sample sizes, medication effects and heterogeneous methods of quantification limit the conclusions that can be drawn, the data is suggestive of higher levels of cortical D1-R in drug naïve patients with psychosis, and lower D1-R in patients with affective disorders. Data sharing and reanalysis using harmonized methodology are important next steps towards clarifying the role of D1-R in these disorders.
D1; Depression; Dopamine; PET; Schizophrenia; Substance use disorder
Self-harm is common in youth and an important risk factor for suicide. Certain self-harm methods might indicate a higher risk of suicide. The main aim of this study was to determine whether some methods of self-harm in adolescents (10-17 years) and young adults (18-24 years) are associated with a particularly high risk of suicide. A secondary aim was to ascertain how different self-harm methods might affect the probability of psychiatric follow-up.
Five Swedish registers were linked in a national population-based cohort study. All nonfatal self-harm events recorded in specialist health care, excluding psychiatry and primary care services, among 10-24 year olds between 2000 and 2009 were included. Methods were classified as poisoning, cutting/piercing, violent method (gassing, hanging, strangulation/suffocation, drowning, jumping and firearms), other and multiple methods. Hazard Ratios (HR) for suicide were calculated in Cox regression models for each method with poisoning as the reference. Odds Ratios (OR) for psychiatric inpatient care were determined in logistic regression models. Analyses were adjusted for important covariates and stratified by age group and treatment setting (inpatient/outpatient).
Among adolescents with initial medical hospitalisation, use of a violent method was associated with a near eightfold increase in HR for suicide compared to self-poisoning in the adjusted analysis [HR 7.8; 95% confidence interval (CI) 3.2-19.0]. Among hospitalised young adult women, adjusted HRs were elevated fourfold for both cutting [4.0 (1.9-8.8)] and violent methods [3.9 (1.5-10.6)]. Method of self-harm did not affect suicide risk in young adult men. Adolescents using violent methods had an increased probability of psychiatric inpatient care following initial treatment for self-harm.
Violent self-harm requiring medical hospitalisation may signal particularly high risk of future suicide in adolescents (both sexes) and in young adult women. For the latter group this is the case for cutting requiring hospitalisation as well.
© 2018 Association for Child and Adolescent Mental Health.
Adolescence; epidemiology; mental health; self-harm; suicide
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Body dysmorphic disorder (BDD) usually begins during adolescence but little is known about the prevalence, etiology, and patterns of comorbidity in this age group. We investigated the prevalence of BDD symptoms in adolescents and young adults. We also report on the relative importance of genetic and environmental influences on BDD symptoms, and the risk for co-existing psychopathology.
Prevalence of BDD symptoms was determined by a validated cut-off on the Dysmorphic Concerns Questionnaire (DCQ) in three population-based twin cohorts at ages 15 (n = 6968), 18 (n = 3738), and 20-28 (n = 4671). Heritability analysis was performed using univariate model-fitting for the DCQ. The risk for co-existing psychopathology was expressed as odds ratios (OR).
The prevalence of clinically significant BDD symptoms was estimated to be between 1 and 2% in the different cohorts, with a significantly higher prevalence in females (1.3-3.3%) than in males (0.2-0.6%). The heritability of body dysmorphic concerns was estimated to be 49% (95% CI 38-54%) at age 15, 39% (95% CI 30-46) at age 18, and 37% (95% CI 29-42) at ages 20-28, with the remaining variance being due to non-shared environment. ORs for co-existing neuropsychiatric and alcohol-related problems ranged from 2.3 to 13.2.
Clinically significant BDD symptoms are relatively common in adolescence and young adulthood, particularly in females. The low occurrence of BDD symptoms in adolescent boys may indicate sex differences in age of onset and/or etiological mechanisms. BDD symptoms are moderately heritable in young people and associated with an increased risk for co-existing neuropsychiatric and alcohol-related problems.
Body dysmorphic disorder; comorbidity; heritability; obsessive-compulsive disorder; prevalence; twin study
Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.
dopamine; neuroreceptors; personality traits; positron emission tomography; psychiatric disorders; serotonin
Asylum seekers have increased risk of suicide and suicidal behavior, with differences related to origin, gender, and age. There are barriers to communication in clinical encounters between asylum seekers and clinicians. There is insufficient knowledge about how communication in the clinical encounter affects the suicide risk in female asylum seekers.
To explore the documented communication between female asylum-seeking suicide attempters and clinicians and how it affects treatment.
The medical records of 18 asylum-seeking women who had attempted suicide were analyzed with content analysis.
Communication between patients and clinicians was affected by: the unbearable realities of the women; difficulties for clinicians in decoding languages of distress, and understanding trauma and subjective meanings of suicide; challenges of combining patients' and clinicians' perspectives; and a sense of shared powerlessness.
The medical records did not give direct access to the patient's experience, only to the patient as documented by the clinician.
The results suggest that clinicians working with asylum seekers who have attempted suicide need to develop an understanding of social and cultural factors and of trauma issues. A question for further study is how an enhanced integration of context and subjectivity in psychiatric practice would equip clinicians for the specific challenges encountered.
asylum seekers; cultural idioms of distress; gender; suicidal behavior; trauma
This is the fourth and final study 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 investigate aspects of functioning and environment of individuals with ADHD as documented by the ICF-CY in clinical practice settings. An international cross-sectional multi-centre study was applied, involving nine units from eight countries: Denmark, Germany, India, Italy, Portugal, Saudi Arabia, Sweden and Taiwan. Clinicians and clinical researchers rated the functioning level of 112 children, adolescents and adults with ADHD using the extended ICF-CY checklist version 2.1a. The ratings were based on a variety of information sources, such as medical records, medical history, clinical observations, clinical questionnaires, psychometric tests and structured interviews with participants and family members. In total, 113 ICF-CY categories were identified, of which 50 were related to the activities and participation, 33 to environmental factors and 30 to body functions. The clinical study also yielded strengths related to ADHD, which included temperament and personality functions and recreation and leisure. The study findings endorse the complex nature of ADHD, as evidenced by the many functional and contextual domains impacted in ADHD. ICF-CY based tools can serve as foundation for capturing various functional profiles and environmental facilitators and barriers. The international nature of the ICF-CY makes it possible to develop user-friendly tools that can be applied globally and in multiple settings, ranging from clinical services and policy-making to education and research.
ADHD; Assessment; Clinical study; DSM; Functioning; ICD; Neurodevelopmental disorder; Psychiatry; Quality of life
For children with oppositional defiant disorder (ODD), Parent Management Training (PMT) is a recommended treatment in addition to child Cognitive Behavioral Therapy (child-CBT). There is however a lack of studies investigating the additive effect of group-based child-CBT to PMT for children between 8 and 12 years. The current study investigated the incremental effect of group-based child-CBT, based on the Coping Power Program, when added to the Swedish group-based PMT program KOMET. Outcomes were child behavior problems, child prosocial behavior, parenting skills and the moderating effect of child characteristics. One hundred and twenty children 8-12 years with ODD or Disruptive Behavioral Disorder NOS and their parents were randomized either to combined child-CBT and PMT (n = 63) or to PMT only (n = 57) in Swedish Child- and Adolescent Psychiatric settings. Participants were assessed pre- and post-treatment using semi-structured interviews and child- and parent ratings. After treatment, behavior problems were reduced in both groups. Prosocial behavior were significantly more improved in the combined treatment. Parenting skills were improved in both groups. In moderator analyses, behavior problems and prosocial behavior improved significantly more in the combined treatment compared to PMT only in the group of children with high levels of ODD symptoms.
Child problem-solving skills training; ISRCTN10834473; Intervention; Moderators; Oppositional defiant disorder; Parent training; RCT
The imaging of biomarkers for characterization of dopaminergic impairment in Parkinson's disease (PD) is useful for diagnosis, patient stratification, and assessment of treatment outcomes. [18 F]FE-PE2I is an improved imaging tool allowing for detailed mapping of the dopamine transporter protein in the nigro-striatal system at the level of cell bodies (substantia nigra), axons, and presynaptic terminals (striatum).
The objective of this study was to compare the dopamine transporter protein loss in the presynaptic terminals to that in the cell bodies and axons in early PD patients using [18 F](E)-N-(3-iodoprop-2-enyl)-2b-carbofluoroethoxy-3b-(4'-methyl-phenyl) nortropane ([18 F]FE-PE2I) and high-resolution PET.
A total of 20 early PD patients (15 men/5 women, 62 ± 8 years) and 20 controls (15 men/5 women, 62 ± 7 years) underwent high-resolution [18 F]FE-PE2I PET. Dopamine transporter protein availability was estimated for the different nigro-striatal regions and expressed as nondisplaceable binding potential values.
When compared with controls, the binding potential values in PD patients were reduced by 36% to 70% in presynaptic terminals and by 30% in cell bodies. Dopamine transporter availability along the tracts was not different between the 2 groups (controls 0.5 ± 0.1 vs PD 0.4 ± 0.1).
This is the first study that examines dopamine transporter protein availability in vivo within the entire nigro-striatal pathway. The results suggest that at early stages of symptomatic PD a greater loss is observed at the level of the axonal terminals when compared with cell bodies and axons of dopaminergic neurons. The findings suggest a relative preservation of cell bodies in early PD, which might be relevant for novel disease-modifying strategies. © 2018 International Parkinson and Movement Disorder Society.
© 2018 International Parkinson and Movement Disorder Society.
PET imaging; Parkinson's disease; dopamine transporter protein (DAT); nigro-striatal degeneration; substantia nigra
Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairments in social, educational, and occupational functioning, as well as specific strengths. Currently, there is no internationally accepted standard to assess the functioning of individuals with ADHD. WHO's International Classification of Functioning, Disability and Health-child and youth version (ICF) can serve as a conceptual basis for such a standard. The objective of this study is to develop a comprehensive, a common brief, and three age-appropriate brief ICF Core Sets for ADHD. Using a standardised methodology, four international preparatory studies generated 132 second-level ICF candidate categories that served as the basis for developing ADHD Core Sets. Using these categories and following an iterative consensus process, 20 ADHD experts from nine professional disciplines and representing all six WHO regions selected the most relevant categories to constitute the ADHD Core Sets. The consensus process resulted in 72 second-level ICF categories forming the comprehensive ICF Core Set-these represented 8 body functions, 35 activities and participation, and 29 environmental categories. A Common Brief Core Set that included 38 categories was also defined. Age-specific brief Core Sets included a 47 category preschool version for 0-5 years old, a 55 category school-age version for 6-16 years old, and a 52 category version for older adolescents and adults 17 years old and above. The ICF Core Sets for ADHD mark a milestone toward an internationally standardised functional assessment of ADHD across the lifespan, and across educational, administrative, clinical, and research settings.
ADHD; Assessment; Consensus conference; DSM; Functioning; ICD; ICF Core Sets; Psychiatry
This is the fourth international preparatory study designed to develop International Classification of Functioning, Disability and Health (ICF, and Children and Youth version, ICF-CY) Core Sets for Autism Spectrum Disorder (ASD). Examine functioning of individuals diagnosed with ASD as documented by the ICF-CY in a variety of clinical settings. A cross-sectional study was conducted, involving 11 units from 10 countries. Clinical investigators assessed functioning of 122 individuals with ASD using the ICF-CY checklist. In total, 139 ICF-CY categories were identified: 64 activities and participation, 40 body functions and 35 environmental factors. The study results reinforce the heterogeneity of ASD, as evidenced by the many functional and contextual domains impacting on ASD from a clinical perspective.
ASD; Assessment; Clinical study; DSM; Functioning; ICD; Neurodevelopmental disorder
Hoarding disorder (HD) is difficult to treat. In an effort to increase efficacy and engagement in cognitive-behavioral therapy (CBT), we developed and evaluated a novel intervention comprising group CBT combined with between-session Internet-based clinician support for people with HD.
Twenty participants with HD received group CBT combined with an Internet-support system enabling therapist-participant communication between group sessions.
The treatment was associated with a significant reduction on the Saving Inventory-Revised (SI-R) and a large effect size (Cohen's d = 1.57) was found at posttreatment. Treatment gains were maintained at the 3-month follow-up. Group attendance was high and no participants dropped out from treatment prematurely. Between-session motivational support from the therapist was most frequently mentioned as the main strength of the system.
The results of this study support adding Internet-based clinician support to group CBT for HD to increase treatment adherence and, potentially, improve the overall efficacy of CBT.
© 2018 Wiley Periodicals, Inc.
behavioral group therapy; cognitive-behavioral therapy; hoarding; internet-based interventions
There is a scarcity of clinical trials on psychological treatments for concurrent borderline personality disorder (BPD) and substance use disorder (SUD). Mentalization-based treatment (MBT) have shown efficacy in several trials on BPD. The aim of the present study was to examine the feasibility and effectiveness of MBT for concurrent BPD and SUD.
Patients (n = 46) with concurrent BPD and SUD were randomized either to MBT in combination with SUD treatment (n = 24) or to SUD treatment alone (n = 22). Outcome was measured after 18 months using objective data, as well as interview and self-report measures.
There was no significant difference between the groups on any outcome variable. No suicide attempts occurred in the MBT group in contrast to 4 suicide attempts that occurred in the control group - a difference that did not reach statistical significance (p = 0.06). A majority of the therapists did not show sufficient MBT adherence and quality.
MBT for patients with concurrent BPD and SD does not appear to be harmful; on the other hand, it is possibly helpful in reducing the risk involved in suicide attempts.
© 2018 The Author(s) Published by S. Karger AG, Basel.
Borderline personality disorder; Psychotherapy; Randomized controlled trial; Substance-related disorders
We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient. The achieved spatial resolution, close to 1 mm, will enable differentiation of relevant brain structures for schizophrenia. A cost-effective and simple method of radiopharmaceutical production from 11C-carbon monoxide and a mini-clean room has been demonstrated. It has been shown that 11C-raclopride has higher binding potential in a new VAAT null mutant mouse model of schizophrenia compared to wild type control animals. A significant reduction in TSPO binding has been found in gray matter in a small sample of drug-naïve, first episode psychosis patients, suggesting a reduced number or an altered function of immune cells in brain at early stage schizophrenia.
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
Iran is a developing and Islamic country where the consumption of alcoholic beverages is banned. However, psychiatric disorders and alcohol use disorders are often co-occurring. We used the Alcohol Use Disorders Identification Test (AUDIT) to estimate the prevalence of alcohol use and examined the psychometric properties of the test among psychiatric outpatients in Teheran, Iran.
AUDIT was completed by 846 consecutive (sequential) patients. Descriptive statistics, internal consistency (Cronbach alpha), confirmatory and exploratory factor analyses were used to analyze the prevalence of alcohol use, reliability and construct validity.
12% of men and 1% of women were hazardous alcohol consumers. Internal reliability of the Iranian version of AUDIT was excellent. Confirmatory factor analyses showed that the construct validity and the fit of previous factor structures (1, 2 and 3 factors) to data were not good and seemingly contradicted results from the explorative principal axis factoring, which showed that a 1-factor solution explained 77% of the co-variances.
We could not reproduce the suggested factor structure of AUDIT, probably due to the skewed distribution of alcohol consumption. Only 19% of men and 3% of women scored above 0 on AUDIT. This could be explained by the fact that alcohol is illegal in Iran. In conclusion the AUDIT exhibited good internal reliability when used as a single scale. The prevalence estimates according to AUDIT were somewhat higher among psychiatric patients compared to what was reported by WHO regarding the general population.
Alcohol Use Disorders Identification Test (AUDIT); Alcohol use disorder; Prevalence; Psychometric properties
The histamine subtype-3 receptor (H3R) is implicated in a range of central nervous system disorders, and several radioligands have been developed for H3R positron emission tomography imaging. However, a limitation of currently used PET radioligands for H3R is the slow binding kinetics in high density brain regions. To address this, we herein report the development of three novel candidate H3R radioligands, namely, [ carbonyl-11C]AZ13153556 ([ carbonyl-11C]4), [ carbonyl-11C]AZD5213([ carbonyl-11C]5), and [ carbonyl-11C]AZ13198083 ([ carbonyl-11C]6), and their subsequent preclinical evaluation in nonhuman primates (NHP). Radioligands [ carbonyl-11C]4-6 were produced and isolated in high radioactivity (>1000 MBq), radiochemical purity (>99%), and moderate molar activity (19-28 GBq/μmol at time of injection) using a palladium-mediated 11C-aminocarbonylation protocol. All three radioligands showed high brain permeability as well as a regional brain radioactivity distribution in accordance with H3R expression (striatum > cortex > cerebellum). [ Carbonyl-11C]6 displayed the most favorable in vivo kinetics and brain uptake, with an early peak in the striatal time-activity curve followed by a progressive washout from the brain. The specificity and on-target kinetics of [ carbonyl-11C]6 were next investigated in pretreatment and displacement studies. After pretreatment or displacement with 5 (0.1 mg/kg), a uniformly low distribution of radioactivity across the NHP brain was observed. Collectively, this work demonstrates that [ carbonyl-11C]6 is a promising candidate for H3R imaging in human subjects.
PET imaging; carbon-11; carbonylation; histamine; radioligand; receptor
Effective multisensory processing develops in infancy and is thought to be important for the perception of unified and multimodal objects and events. Previous research suggests impaired multisensory processing in autism, but its role in the early development of the disorder is yet uncertain. Here, using a prospective longitudinal design, we tested whether reduced visual attention to audiovisual synchrony is an infant marker of later-emerging autism diagnosis.
We studied 10-month-old siblings of children with autism using an eye tracking task previously used in studies of preschoolers. The task assessed the effect of manipulations of audiovisual synchrony on viewing patterns while the infants were observing point light displays of biological motion. We analyzed the gaze data recorded in infancy according to diagnostic status at 3 years of age (DSM-5).
Ten-month-old infants who later received an autism diagnosis did not orient to audiovisual synchrony expressed within biological motion. In contrast, both infants at low-risk and high-risk siblings without autism at follow-up had a strong preference for this type of information. No group differences were observed in terms of orienting to upright biological motion.
This study suggests that reduced orienting to audiovisual synchrony within biological motion is an early sign of autism. The findings support the view that poor multisensory processing could be an important antecedent marker of this neurodevelopmental condition.
© 2018 Association for Child and Adolescent Mental Health.
Autism spectrum disorder; biological motion; biomarker; infancy; multisensory processing; scientific replication
Cognitive behavioral therapy (CBT) is an evidence-based method for treating specific phobias, but access to treatment is difficult, especially for children and adolescents with dental anxiety. Psychologist-guided Internet-based CBT (ICBT) may be an effective way of increasing accessibility while maintaining treatment effects.
The aim of this study was to test the hypothesis that psychologist-guided ICBT improves school-aged children's and adolescents' ability to manage dental anxiety by (1) decreasing avoidance and affecting the phobia diagnosis and (2) decreasing the dental fear and increasing the target groups' self-efficacy. The study also aimed to examine the feasibility and acceptability of this novel treatment.
This was an open, uncontrolled trial with assessments at baseline, posttreatment, and the 1-year follow-up. The study enrolled and treated 18 participants. The primary outcome was level of avoidance behaviors, as measured by the picture-guided behavioral avoidance test (PG-BAT). The secondary outcome was a diagnostic evaluation with the parents conducted by a psychologist. The specific phobia section of the structured interview Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime (K-SADS-PL) was used. Other outcome measures included level of dental anxiety and self-efficacy. The ICBT, which employed exposure therapy, comprised 12 modules of texts, animations, dentistry-related video clips, and an exercise package (including dental instruments). Participants accessed the treatment through an Internet-based treatment platform and received Web-based guidance from a psychologist. Treatment also included training at dental clinics. Feasibility and acceptability were assessed by measures of engagement, adherence, compliance, completed measures, patient and parent satisfaction scale, and staff acceptability.
The level of avoidance (according to the primary outcome measure PG-BAT) and dental anxiety decreased and self-efficacy increased significantly (P<.001), within-group effect sizes for both the primary outcome (Cohen d=1.5), and other outcomes were large in the range of 0.9 and 1.5. According to K-SADS-PL, 53% (8/15) of the participants were free from diagnosable dental anxiety at the 1-year follow-up. At the 1-year follow-up, improvements were maintained and clinically significant, with 60% (9/15) of participants who had been unable to manage intraoral injection of local anesthetics before ICBT reporting having accomplished this task at a dental clinic. The target group showed improvement in all the outcome measures. High levels of feasibility and acceptability were observed for the treatment.
ICBT is a promising and feasible treatment for dental anxiety in children and adolescents. Integrating it into routine pediatric dental care would increase access to an effective psychological treatment. The results of this open trial must be replicated in controlled studies.
©Shervin Shahnavaz, Erik Hedman-Lagerlöf, Tove Hasselblad, Lena Reuterskiöld, Viktor Kaldo, Göran Dahllöf. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.01.2018.
cognitive behavioral therapy; dental fear; dental phobia; dentistry; internet-based treatment; pediatric dentistry; psychology; self efficacy
Alzheimer's disease (AD) is characterized by accumulation of β-amyloid (Aβ) plaques and neurofibrillary tau tangles in the brain. β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a key role in the generation of Aβ fragments via extracellular cleavage of the amyloid precursor protein (APP). We became interested in developing a BACE1 PET ligand to facilitate clinical assessment of BACE1 inhibitors and explore its potential in the profiling and selection of patients for AD trials. Using a set of PET ligand design parameters, compound 3 (PF-06684511) was rapidly identified as a lead with favorable in vitro attributes and structural handles for PET radiolabeling. Further evaluation in an LC-MS/MS "cold tracer" study in rodents revealed high specific binding to BACE1 in brain. Upon radiolabeling, [18F]3 demonstrated favorable brain uptake and high in vivo specificity in nonhuman primate (NHP), suggesting its potential for imaging BACE1 in humans.
Psychosis is a heterogeneous psychiatric condition for which a multitude of risk and protective factors have been suggested. This umbrella review aimed to classify the strength of evidence for the associations between each factor and psychotic disorders whilst controlling for several biases. The Web of Knowledge database was searched to identify systematic reviews and meta-analyses of observational studies which examined associations between socio-demographic, parental, perinatal, later factors or antecedents and psychotic disorders, and which included a comparison group of healthy controls, published from 1965 to January 31, 2017. The literature search and data extraction followed PRISMA and MOOSE guidelines. The association between each factor and ICD or DSM diagnoses of non-organic psychotic disorders was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of psychotic cases, random-effects p value, largest study 95% confidence interval, heterogeneity between studies, 95% prediction interval, small study effect, and excess significance bias. In order to assess evidence for temporality of association, we also conducted sensitivity analyses restricted to data from prospective studies. Fifty-five meta-analyses or systematic reviews were included in the umbrella review, corresponding to 683 individual studies and 170 putative risk or protective factors for psychotic disorders. Only the ultra-high-risk state for psychosis (odds ratio, OR=9.32, 95% CI: 4.91-17.72) and Black-Caribbean ethnicity in England (OR=4.87, 95% CI: 3.96-6.00) showed convincing evidence of association. Six factors were highly suggestive (ethnic minority in low ethnic density area, second generation immigrants, trait anhedonia, premorbid IQ, minor physical anomalies, and olfactory identification ability), and nine were suggestive (urbanicity, ethnic minority in high ethnic density area, first generation immigrants, North-African immigrants in Europe, winter/spring season of birth in Northern hemisphere, childhood social withdrawal, childhood trauma, Toxoplasma gondii IgG, and non-right handedness). When only prospective studies were considered, the evidence was convincing for ultra-high-risk state and suggestive for urbanicity only. In summary, this umbrella review found several factors to be associated with psychotic disorders with different levels of evidence. These risk or protective factors represent a starting point for further etiopathological research and for the improvement of the prediction of psychosis.
Black-Caribbean ethnicity; Schizophrenia; antecedents; environment; parental factors; perinatal factors; psychosis; risk; socio-demographic factors; ultra-high-risk state for psychosis; urbanicity
18F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl-phenyl) nortropane (18F-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for 18F-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of 18F-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 μGy/MBq), followed by the liver (46 μGy/MBq). The effective dose was 23 μSv/MBq (range, 19-28 μSv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that 18F-FE-PE2I is a suitable radioligand for DAT imaging.
18F-FE-PE2I; DAT; biodistribution; dosimetry; effective dose
To investigate if treatment for alcohol dependence in primary care is as effective as specialist addiction care.
Randomized controlled non-inferiority trial, between groups parallel design, not blinded. The non-inferiority limit was set to 50 grams of alcohol per week. About 288 adults fulfilling ICD-10 criteria for alcohol dependence were randomized to treatment in primary care (men n = 82, women n = 62) or specialist care (men n = 77, women n = 67). General practitioners at 12 primary care centers received 1-day training in a treatment manual for alcohol dependence. Primary outcome was change in weekly alcohol consumption at 6-months follow-up compared with baseline, as measured with timeline follow back. Secondary outcomes were heavy drinking days, severity of dependence, consequences of drinking, psychological health, quality of life, satisfaction with treatment and biomarkers.
Intention-to-treat analysis (n = 228) was statistically inconclusive, and could not confirm non-inferiority for the primary outcome, since the high end of the confidence interval exceeded 50 grams (estimated mean weekly alcohol consumption was 30 grams higher in primary care compared with specialist care; 95% confidence interval -10.20; 69.72). However, treatment in specialist care was not significantly superior to primary care (P = 0.146). Subanalysis suggests that specialist care was superior to primary care only for patients with high severity of dependence.
Treatment for alcohol dependence in primary care is a promising approach, especially for individuals with low to moderate dependence. This may be a way to broaden the base of treatment for alcohol dependence, reducing the current treatment gap.
Psychiatric disorders are common in paediatric patients with chronic pain, but the overall prevalence of comorbid neurodevelopmental disorders is unclear. We report on a case of severe chronic pain in a child with undiagnosed comorbid autism spectrum disorder and attention deficit hyperactivity disorder, where significant improvements in pain and function occurred following methylphenidate medication and parental behavioural training.
The inclusion of behavioural assessment and screening for neurodevelopmental comorbidity may be essential in addressing complex paediatric chronic pain.
©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Attention deficit hyperactivity disorder; Autism; Behaviour analysis; Chronic pain; Comorbidity
Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate. We analyzed the largest genome-wide association studies of schizophrenia and lung, breast, prostate, ovary, and colon-rectum cancer including more than 220,000 subjects, and included genetic association with smoking behavior. Polygenic enrichment of associations with lung cancer was observed in schizophrenia, and weak enrichment for the remaining cancer sites. After excluding the major histocompatibility complex region, we identified three independent loci jointly associated with schizophrenia and lung cancer. The strongest association included nicotinic acetylcholine receptors and is an established pleiotropic locus shared between lung cancer and smoking. The two other loci were independent of genetic association with smoking. Functional analysis identified downstream pleiotropic effects on epigenetics and gene-expression in lung and brain tissue. These findings suggest that genetic factors may explain partly the observed epidemiological association of lung cancer and schizophrenia.
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
Given the significant impact epilepsy can have on health-related quality of life (HRQoL) of individuals with this condition and their families, there is great clinical interest in evidence-based psychological treatments aimed at enhancing well-being in people with epilepsy (PWE). An evaluation of the current evidence is needed to assess the effects of psychological treatments for PWE on HRQoL outcomes to inform future therapeutic recommendations and research designs.
The operational definition of psychological treatments included a broad range of interventions that use psychological or behavioral techniques designed to improve HRQoL, psychiatric comorbidities, and seizure frequency and severity for adults and children with epilepsy. A systematic literature search was conducted in line with Cochrane criteria for randomized controlled trials (RCTs) and quasi-RCTs investigating psychological treatments and using HRQoL outcome measures as primary or secondary outcome measures. Standard methodological procedures required by the Cochrane Collaboration were used for data collection and analysis.
Twenty-four completed RCTs were included in this review (2439 participants). Based on satisfactory methodological homogeneity, data from 9 studies (468 participants) providing Quality of Life in Epilepsy-31 (QOLIE-31) outcomes were pooled for meta-analyses, showing significant mean changes for QOLIE-31 total score and 6 subscales. The significant mean changes of QOLIE-31 total score (mean improvement of 5.68 points; 95% confidence interval = 3.11-8.24, P < .0001) and 3 subscales (emotional well-being, energy/fatigue, overall quality of life [QoL]) exceeded the threshold of minimally important change, indicating a clinically meaningful postintervention improvement of QoL. Overall, the meta-analysis quality of evidence was characterized as "moderate" due to the risk of bias present in 8 of the 9 included studies (Handbook for Systematic Reviews of Interventions, Version 5.1.0, 2011, Chapters 8 and 12). A narrative synthesis was conducted for all trials and outcomes that were not entered in the meta-analysis.
These results provide moderate-quality evidence that psychological treatments for adults with epilepsy may enhance HRQoL in people with epilepsy.
Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.
anxiety; depression; nonadherence; psychoeducation; self-management
Recent research suggests that having a newborn child is associated with substantially reduced risk for maternal suicide. We studied postpartum suicides in a national cohort of mothers and the role of mental disorder, self-harm and delivery related factors.
We used a nested case-control design with data from Swedish registries. The cohort consisted of all women given birth in Sweden 1974-2009. Mothers who died by suicide during follow-up were considered cases (n = 1,786) and risk of suicide was estimated with proximity to delivery as the explanatory variable. In a second step, association between suicide during the first year following delivery (n = 145) and mental disorder, self-harm and delivery related variables risk factors were analyzed.
The first postpartum year was associated with a lower risk of suicide, compared to later (RR 0.80, 95%CI 0.66-0.96), which was unaltered after adjustment for socio-economic status and history of self-harm (aRR 0.82, 95%CI 0.68-0.99). Compared to living mothers, suicide victims of the postpartum year more often had affective disorders (aRR 133.94, 95%CI 45.93-390.61), psychotic disorders (aRR 83.69, 95%CI 36.99-189.31) and history of self-harm (aRR 47.56, 95%CI 18.24-124.02). The aRR of stillbirth was 2.66 (95%CI 0.63-11.30).
We found only a weak negative association between childbirth during the preceding year and suicide, when using mothers as controls. A severe mental disorder after delivery and a history of self-harm was strongly associated with increased risk of suicide in the postpartum year and may inform the clinical assessment postpartum.
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
Systematic reviews and meta-analyses were completed studying the effect of changes in the physical availability of take-away alcohol on per capita alcohol consumption. Previous reviews examining this topic have not focused on off-premise outlets where take-away alcohol is sold and have not completed meta-analyses.
Systematic reviews were conducted separately for policies affecting the temporal availability (days and hours of sale) and spatial availability (outlet density) of take-away alcohol. Studies were included up to December 2015. Quality criteria were used to select articles that studied the effect of changes in these policies on alcohol consumption with a focus on natural experiments. Random-effects meta-analyses were applied to produce the estimated effect of an additional day of sale on total and beverage-specific consumption.
Separate systematic reviews identified seven studies regarding days and hours of sale and four studies regarding density. The majority of articles included in these systematic reviews, for days/hours of sale (7/7) and outlet density (3/4), concluded that restricting the physical availability of take-away alcohol reduces per capita alcohol consumption. Meta-analyses studying the effect of adding one additional day of sale found that this was associated with per capita consumption increases of 3.4% (95% CI [2.7, 4.1]) for total alcohol, 5.3% (95% CI [3.2, 7.4]) for beer, 2.6% (95% CI [1.8, 3.5]) for wine, and 2.6% (95% CI [2.1, 3.2]) for spirits. The small number of included studies regarding hours of sale and density precluded meta-analysis.
The results of this study suggest that decreasing the physical availability of take-away alcohol will decrease per capita consumption. As decreasing per capita consumption has been shown to reduce alcohol-related harm, restricting the physical availability of take-away alcohol would be expected to result in improvements to public 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
Epigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on 53 young adult males and aimed to determine whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment, and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment.
MAOA-uVNTR genotypes with ≤ 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively.
Carriers of the S allele, who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score in contrast to L-allele carriers. Carriers of the S allele, who reported higher AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers.
Intronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.
Copyright © 2017 by the Research Society on Alcoholism.
MAOA- uVNTR ; Alcohol; DNA Methylation; Gene by Environment; Maltreatment
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.
Reduced dopamine D2 receptor (D2R) ligand binding has repeatedly been demonstrated in the striatum of humans with alcohol use disorder (AUD). The attenuated D2R binding has been suggested to reflect a reduced D2R density, which in turn has been proposed to drive craving and relapse. However, results from rodent studies addressing the effects of alcohol drinking on D2R density have been inconsistent.
A validated alcohol drinking model (intermittent access to 20% alcohol) in Wistar rats was used to study the effects of voluntary alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age-matched alcohol-naïve control rats. Reverse transcriptase quantitative PCR was used to quantify isoform-specific Drd2 gene expression levels. Using bisulfite pyrosequencing, DNA methylation levels of a regulatory region of the Drd2 gene were determined. In situ proximity ligation assay was used to measure densities of D2R receptor complexes: D2R-D2R, adenosine A2A receptor (A2AR)-D2R, and sigma1 receptor (sigma1R)-D2R.
Long-term voluntary alcohol drinking significantly reduced mRNA levels of the long D2R isoform in the nucleus accumbens (NAc) but did not alter CpG methylation levels in the analyzed sequence of the Drd2 gene. Alcohol drinking also reduced the striatal density of D2R-D2R homoreceptor complexes, increased the density of A2AR-D2R heteroreceptor complexes in the NAc shell and the dorsal striatum, and decreased the density of sigma1R-D2R heteroreceptor complexes in the dorsal striatum.
The present results on long-term alcohol drinking might reflect reduced D2R levels through reductions in D2R-D2R homoreceptor complexes and gene expression. Furthermore, based on antagonistic interactions between A2AR and D2R, an increased density of A2AR-D2R heteroreceptor complexes might indicate a reduced affinity and signaling of the D2R population within the complex. Hence, both reduced striatal D2R levels and reduced D2R protomer affinity within the striatal A2AR-D2R complex might underlie reduced D2R radioligand binding in humans with AUD. This supports the hypothesis of a hypodopaminergic system in AUD and suggests the A2AR-D2R heteroreceptor complex as a potential novel treatment target.
Copyright © 2017 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.
Alcohol Dependence; DNA Methylation; Epigenetics; Heteroreceptors and Homoreceptors; Receptor Dimers
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
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
To our knowledge, the association of obsessive-compulsive disorder (OCD) and academic performance has not been objectively quantified.
To investigate the association of OCD with objectively measured educational outcomes in a nationwide cohort, adjusting for covariates and unmeasured factors shared between siblings.
This population-based birth cohort study included 2 115 554 individuals who were born in Sweden between January 1, 1976, and December 31, 1998, and followed up through December 31, 2013. Using the Swedish National Patient Register and previously validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, we identified persons with OCD; within the cohort, we identified 726 198 families with 2 or more full siblings, and identified 11 482 families with full siblings discordant for OCD. Data analyses were conducted from October 1, 2016, to September 25, 2017.
The study evaluates the following educational milestones: eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, finishing a university degree, and finishing postgraduate education.
Of the 2 115 554 individuals in the cohort, 15 120 were diagnosed with OCD (59% females). Compared with unexposed individuals, those with OCD were significantly less likely to pass all core and additional courses at the end of compulsory school (adjusted odds ratio [aOR] range, 0.35-0.60) and to access a vocational or academic program in upper secondary education (aOR, 0.47; 95% CI, 0.45-0.50 and aOR, 0.61; 95% CI, 0.58-0.63, for vocational and academic programs, respectively). People with OCD were also less likely to finish upper secondary education (aOR, 0.43; 95% CI, 0.41-0.44), start a university degree (aOR, 0.72; 95% CI, 0.69-0.75), finish a university degree (aOR, 0.59; 95% CI, 0.56-0.62), and finish postgraduate education (aOR, 0.52; 95% CI, 0.36-0.77). The results were similar in the sibling comparison models. Individuals diagnosed with OCD before age 18 years showed worse educational attainment across all educational levels compared with those diagnosed at or after age 18 years. Exclusion of patients with comorbid neuropsychiatric disorders, psychotic, anxiety, mood, substance use, and other psychiatric disorders resulted in attenuated estimates, but patients with OCD were still impaired across all educational outcomes.
Obsessive-compulsive disorder, particularly when it has an early onset, is associated with a pervasive and profound decrease in educational attainment, spanning from compulsory school to postgraduate education.
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
Fibromyalgia (FM) is a common and disabling chronic pain disorder, for which existing pharmacological and psychological treatments have yet yielded insufficient effects. Previous literature has shown that exposure therapy may be an effective treatment for chronic pain. This study constitutes the first randomized controlled trial evaluating exposure therapy for FM.
A total of 140 participants with diagnosed FM were randomized to a 10-week Internet-delivered exposure treatment (iExp; n=70) or a waitlist control condition (WLC; n=70). Primary outcome measure were FM symptoms and impact, and secondary outcome measures were fatigue, disability, quality of life, pain-related distress and avoidance behaviors, insomnia, depression, and anxiety.
Data retention was high (100% data completion at posttreatment for primary outcome, 96% at 6-month follow-up and 94% at 12-month follow-up). Results showed that participants in the iExp group made large and superior improvements compared with WLC on FM symptoms and impact (B, -1.93; z, -10.14; P<0.001, between-group Cohen d=0.90), as well as all secondary outcomes (between-group Cohen d ranging from 0.44 to 1.38) with sustained results.
We conclude that iExp seems to be an efficacious treatment for FM compared with no treatment, and the results also highlight the potential increase of accessibility by using the Internet format to deliver psychological treatments for these patients. Future trials with active control conditions are warranted.
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
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.
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
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
Positron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BPND) of [11C]raclopride in NHP.
Three cynomolgus monkeys underwent two to three PET measurements with [11C]raclopride under continuous sevoflurane anesthesia on the same day. The concentration of sevoflurane was adjusted according to the general conditions and safety parameters of the NHP. Time to peak (TTP) radioactivity in the striatum was estimated from time-activity curves (TACs). The BPND in the striatum was calculated by the simplified reference tissue model using the cerebellum as reference region.
In each NHP, the TTP became shorter in the later PET measurements than in the first one. Across all measurements (n = 8), concentration of sevoflurane correlated with TTP (Spearman's ρ = - 0.79, p = 0.03), but not with BPND (ρ = - 0.25, p = 0.55).
These data suggest that sevoflurane affects the shape of TACs but has no evident effect on BPND in consecutive PET measurements.
Binding potential; Positron emission tomography; Sevoflurane; Time to peak; Time-activity curve; [11C]Raclopride
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.
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
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
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
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.
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
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.
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.