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Abstract Background Common clinical sense would suggest that individuals with milder obsessive-compulsive disorder (OCD) symptoms should be the most suitable for guided internet-delivered cognitive behaviour therapy (CBT), with more intensive forms of treatment reserved for more severe or complex cases. Results In this secondary data analysis of a non-inferiority clinical trial comparing internet-delivered CBT with in-person CBT for young people with OCD (N = 152), we found that higher baseline symptom severity predicted worse treatment outcomes in the in-person group but not the internet-delivered CBT group. Additional analyses showed that among individuals with milder symptoms, internet-delivered CBT was associated with worse outcomes than in-person CBT. Conclusions If replicated, these results would question the axiom that internet-delivered CBT is most suitable for milder cases. Trial registration The original trial was registered at ClinicalTrials.gov ID NCT03263546. Date of registration 2017–08–28.

Few studies have evaluated the implementation of ICBT in regular child and adolescent mental health services (CAMHS). This study aimed to explore the acceptability, feasibility, and effectiveness of ICBT for children and adolescents with anxiety disorders and obsessive-compulsive disorder (OCD) within a rural CAMHS. The study also explored outcome predictors and long-term outcomes.Eighty-three participants were consecutively recruited from a non-specialized CAMHS in Region Jämtland Härjedalen in northern Sweden. Therapist-guided ICBT was offered during 12 weeks to children aged 8–17 with an anxiety disorder or OCD. Acceptability and feasibility measures included treatment adherence, treatment satisfaction, and adverse events. The primary outcome measure was the Clinical Global Impression–Severity. Secondary measures of effectiveness included clinician-, self-, and parent-ratings of symptom severity and functional impairment. Assessments were completed at baseline, post-treatment, and three-month follow-up (primary endpoint). A two-year follow up was conducted using medical records. Potential predictors included both patient characteristics and treatment variables.Results indicated that ICBT was both acceptable and feasible according to study measures. Statistically significant improvements were found from baseline to the three-month follow-up on clinician rated severity (B [SE] = −0.92 [0.09]; p

Abstract Background Obsessive-compulsive disorder (OCD) has been associated with a broad range of health-related issues. Unhealthy lifestyle habits such as physical inactivity, an unhealthy diet, smoking, and alcohol consumption are hypothesized to contribute to this association. However, the lifestyle habits of individuals with OCD have been scarcely investigated. In this international survey, we explored the physical health and lifestyle habits of adults with a self-reported diagnosis of OCD. Methods An online global survey available in seven languages was disseminated through interest organizations and social media between July 2021 and March 2022. The survey included questions relating to socio-demographic variables and clinical characteristics (including OCD symptom severity – as measured with the 12-item self-report scale Obsessive-Compulsive Inventory [OCI-12] – and psychotropic medication), physical health, and lifestyle habits. Frequencies and percentages, or means and standard deviations, as appropriate, were calculated. Subgroup analyses by OCD symptom severity, gender, and age group were performed. Results A total of 496 individuals with OCD completed the survey and were included in the analyses (mean age = 36.0 years, SD = 12.5, range 18–79; 78.8% women). Most participants were from Europe (n = 245, 49.4%) and North America (n = 187, 37.7%). OCD symptom severity scores were on the moderate range (OCI-12 mean score = 21.2, SD = 9.1). A majority (n = 354, 71.4%) reported having comorbid somatic health issues, mainly allergies, gastrointestinal conditions, and cardiometabolic conditions. Nearly half of the sample (n = 236, 47.6%) reported a body mass index ≥ 25, corresponding to at least overweight. A significant proportion of the participants reported low physical activity (n = 271, 55.0%), unhealthy dietary habits (n = 182, 36.7%), risk consumption of alcohol (n = 111, 22.3%), and non-restorative sleep (n = 268, 54.0%). Subgroup analyses showed overall similar results across groups, with some exceptions. Conclusions In this sample, individuals with OCD self-reported a range of health-related issues and a number of unhealthy lifestyle behaviors, most prominently a lack of physical activity. Interventions aimed at modifying unhealthy lifestyles to prevent or improve health conditions beyond the psychiatric symptoms should be considered.

Abstract Background Cognitive behavioral therapy (CBT) is a moderately efficacious treatment for hoarding disorder (HD), with most individuals remaining symptomatic after treatment. The Joining Forces Trial will evaluate whether 10 weeks of in-home decluttering can significantly augment the outcomes of group CBT. Methods A randomized controlled trial of in-home decluttering augmentation of group CBT for HD. Adult participants with HD (N = 90) will receive 12 weeks of protocol-based group CBT for HD. After group CBT, participants will be randomized to either 10 weeks of in-home decluttering led by a social services team or a waitlist. The primary endpoint is 10 weeks post-randomization. The primary outcome measures are the self-reported Saving Inventory-Revised and the blind assessor-rated Clutter Image Rating. Participants on the waitlist will cross over to receive the in-home decluttering intervention after the primary endpoint. Data will be analyzed according to intention-to-treat principles. We will also evaluate the cost-effectiveness of this intervention from both healthcare and societal perspectives. Discussion HD is challenging to treat with conventional psychological treatments. We hypothesize that in-home decluttering sessions carried out by personnel in social services will be an efficacious and cost-effective augmentation strategy of group CBT for HD. Recruitment started in January 2021, and the final participant is expected to reach the primary endpoint in December 2024. Trail registration ClinicalTrials.gov NCT04712474. Registered on 15 January 2021

Abstract The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the relevance of all the studies published since 2001, the current study aimed to update the state-of-art knowledge on the field. All published data concerning the genetic epidemiology of OCD from the CENTRAL, MEDLINE, EMBASE, BVS, and OpenGrey databases were searched by two independent researchers until September 30, 2021. To be included, the articles had to fulfill the following criteria: OCD diagnosis provided by standardized and validated instruments; or medical records; inclusion of a control group for comparison and case-control, cohort or twin study designs. The analysis units were the first-degree relatives (FDRs) of OCD or control probands and the co-twins in twin pairs. The outcomes of interest were the familial recurrence rates of OCD and the correlations of OCS in monozygotic compared with dizygotic twins. Nineteen family, twenty-nine twin, and six population-based studies were included. The main findings were that OCD is a prevalent and highly familial disorder, especially among the relatives of children and adolescent probands, that OCD has a phenotypic heritability of around 50%; and that the higher OCS correlations between MZ twins were mainly due to additive genetic or to non-shared environmental components.

Abstract Background The causes of obsessive-compulsive disorder (OCD) remain unknown. Gene-searching efforts are well underway, but the identification of environmental risk factors is at least as important and should be a priority because some of them may be amenable to prevention or early intervention strategies. Genetically informative studies, particularly those employing the discordant monozygotic (MZ) twin design, are ideally suited to study environmental risk factors. This protocol paper describes the study rationale, aims, and methods of OCDTWIN, an open cohort of MZ twin pairs who are discordant for the diagnosis of OCD. Methods OCDTWIN has two broad aims. In Aim 1, we are recruiting MZ twin pairs from across Sweden, conducting thorough clinical assessments, and building a biobank of biological specimens, including blood, saliva, urine, stool, hair, nails, and multimodal brain imaging. A wealth of early life exposures (e.g., perinatal variables, health-related information, psychosocial stressors) are available through linkage with the nationwide registers and the Swedish Twin Registry. Blood spots stored in the Swedish phenylketonuria (PKU) biobank will be available to extract DNA, proteins, and metabolites, providing an invaluable source of biomaterial taken at birth. In Aim 2, we will perform within-pair comparisons of discordant MZ twins, which will allow us to isolate unique environmental risk factors that are in the causal pathway to OCD, while strictly controlling for genetic and early shared environmental influences. To date (May 2023), 43 pairs of twins (21 discordant for OCD) have been recruited. Discussion OCDTWIN hopes to generate unique insights into environmental risk factors that are in the causal pathway to OCD, some of which have the potential of being actionable targets.

Introduction Individual cognitive behavioural therapy (CBT) with exposure and response prevention is an effective treatment for obsessive–compulsive disorder (OCD). However, individual CBT is costly and time-consuming, requiring weekly therapy sessions for 3–4 months. A 4-day intensive version of CBT for OCD delivered in group format has been recently developed in Norway (Bergen 4-day treatment, B4DT). B4DT has shown promising results in several uncontrolled and one small, randomised trial, but its non-inferiority to the gold standard treatment has not been established.Methods and analysis This single-blind, randomised controlled trial including 120 patients (60 per arm) will compare B4DT to individual CBT. The primary outcome is the blind assessor-rated Yale-Brown Obsessive Compulsive Scale (Y-BOCS). We hypothesise that B4DT will be non-inferior to gold standard CBT 15 weeks after treatment start. The non-inferiority margin is set at four points on the Y-BOCS. Secondary outcomes include time to treatment response, cost-effectiveness, response and remission rates, drop-out rates and adverse events.Ethics and dissemination This study has been approved by the Swedish Ethical Review Authority. Hypotheses were specified and analysis code published before data collection started. Results from all analyses will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials and Consolidated Health Economic Evaluation Reporting Standards irrespective of outcome.Trial registration number NCT05608278.

Body dysmorphic disorder (BDD) is a prevalent and impairing psychiatric condition that typically debuts in adolescence and is associated with risky behaviours. The disorder can be effectively treated with cognitive behaviour therapy (CBT). However, CBT for BDD is seldom available primarily due to a shortage of trained therapists. Internet-delivered CBT (ICBT) can be a way to increase treatment availability. The aim of this feasibility trial was to evaluate the feasibility, safety, and preliminary efficacy of a CBT protocol for adolescents with BDD, adapted to be delivered over the Internet with minimal therapist support. A total of 20 participants (12–17-year-olds) meeting criteria for BDD were recruited nationally to a specialist outpatient clinic in Stockholm, Sweden. One participant withdrew consent and their data could not be analysed. Nineteen participants were offered 12 modules of therapist-guided ICBT for BDD and were followed up to 12 months post-treatment. Preliminary efficacy was measured at the a priori primary endpoint (3-month follow-up) and at the 12-month follow-up with the clinician-rated Yale-Brown Obsessive Compulsive Scale Modified for BDD for Adolescents. The treatment was rated as both credible and satisfactory and was associated with a large and statistically significant reduction in BDD symptom severity (d = 2.94). The proportion of participants classified as responders at the primary endpoint was 73.7%, and the proportion of full or partial remitters was 63.2%. The average therapist support time was 8 min per participant per week. Treatment gains continued to accrue up to the 12-month follow-up. Two participants attempted suicide and another two reported non-suicidal self-injuries during the study period. ICBT with minimal therapist support is a feasible, potentially efficacious, and durable treatment for adolescents with BDD. Risky behaviours typical of this patient group should be carefully monitored during treatment.

Background Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants Children aged 9–17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was −2.29 points (95% confidence interval −3.86 to −0.71) in favour of therapy (effect size −0.31, 95% confidence interval −0.52 to −0.10). This effect was sustained throughout to the final follow-up at 18 months (−2.01 points, 95% confidence interval −3.86 to −0.15; effect size −0.27, 95% confidence interval −0.52 to −0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval −£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval −0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms Two serious, unrelated adverse events occurred in the control group. Limitations We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information. Plain language summary It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 9–17 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy. Scientific summary Background Tic disorders including Tourette syndrome and chronic tic disorders are common conditions that affect approximately 1% of the population in the UK. Young people with tics often report substantial impairment, thus it is important that they have access to evidence-based treatment. Face-to-face behavioural therapy (BT) such as exposure and response prevention (ERP) may be offered to some young people. However, due to a lack of trained therapists, there are often difficulties accessing BT, and there is a better need to understand the clinical and cost-effectiveness of the online delivery of such therapy. Objectives The primary objective of this study was to evaluate the clinical effectiveness of therapist-guided, parent-assisted, internet-based ERP BT for tics in young people with tic disorders compared to online psychoeducation. Secondary objectives included (1) optimising the design of the intervention, (2) undertaking an internal pilot, (3) evaluating cost-effectiveness, (4) establishing whether the efficacy is maintained longer term, (5) understanding the mechanisms of impact of the intervention and (6) identifying barriers to implementation. Methods We conducted an individually randomised (1 : 1 ratio), multicentre trial, with an internal pilot and embedded process evaluation. Participants were assigned to either receive online, remotely delivered, therapist- and parent-supported ERP for tics or online, remotely delivered, therapist- and parent-supported psychoeducation for tics. Participants were recruited from the two study sites, 16 patient identification centres in England or could self-refer online via the study webpage or via Tourettes Action (a national charity for tics). The inclusion criteria were age between 9 and 17 years, with tics assessed on the Yale Global Tic Severity Scale (YGTSS), able to provide written informed consent (parental consent for children aged < 16 years) and with a suitable device they could use to access the internet. Exclusion criteria included receiving a therapy for tics in the past 12 months, starting or stopping tic medication within the past 2 months and intellectual disability/substance use/anorexia nervosa/psychosis/suicidality, moderate/severe intellectual disability, risk to self or others or parent or young person unable to speak or read/write English. All potential participants attended a screening/baseline appointment at one of the two study centres. Participants who were eligible and consented were randomised into one of two study groups. In the intervention group participants received 10 weeks of the remotely delivered, therapist-guided ERP behaviour therapy. In the control group participants received 10 weeks of remotely delivered, therapist-guided psychoeducation about tics. Participants completed measures at the mid-treatment point (5 weeks) and at 3 and 6 months (this formed phase 1, per-protocol design). For phase 2 (a naturalist design), follow-up measures were obtained at 12 and 18 months. The primary outcome (at 3 months) was the total tic severity score (TTSS) on the YGTSS. Secondary outcomes included measures of tics (parent tic questionnaire), general difficulties (strengths and difficulties questionnaire), mood and anxiety (moods and feelings questionnaire and Spence Child Anxiety Scale), global functioning (Children’s Global Assessment Scale, Clinical Global Impressions-Improvement), adverse events, need for further treatment, treatment credibility and satisfaction and the Child and Adolescent Version of the Gilles de la Tourette Syndrome Quality of Life Scale. Quality of life [child health utility 9D (CHU9D)] and resource use (modified child and adolescent service use schedule) data were also collected for the economic evaluation. Follow-up assessments were completed online or via telephone/Webex videoconferencing (YGTSS). The trial internal pilot evaluated recruitment rate, engagement with the intervention and retention to the primary outcome at 9 months into the trial and the results were reported to the relevant oversight committees (Trial Steering Committees and Data Monitoring Committee). A sub-sample of parents and young people in the intervention arm, clinicians and therapists were interviewed to explore barriers/facilitators to implementation and refine the intervention for future use, which formed part of the mixed-methods process evaluation. The quantitative data for the process evaluation included intervention usage metrics, clinical and demographic trial data and therapist contacts. Intervention The intervention was delivered via Barninternetprojektet (Child Internet Project; Swedish digital platform) (BIP), a Swedish web-based digital platform. The BT intervention (ERP) was translated from the Swedish original intervention (BIP TIC), refined and adapted for UK use by our trial team. The active control intervention (psychoeducation) was created by our trial team. Both interventions consisted of 10 web-based chapters, designed to last 10 weeks. Participants had regular contact with a therapist during this time via messages that could be sent inside the treatment platform (resembling an email). The therapist’s role was to give specific feedback to motivate the patient and not to deliver therapeutic content. The young person and the parent/carer were provided with their own separate logins to the BIP platform. For both the intervention and the comparator, treatment completion was defined as completion of the first four child chapters. Results The trial recruited and retained participants exceeding the pre-specified criteria for the internal pilot and therefore proceeded to the full trial. In total 445 candidates signed up to the study and were assessed for eligibility, of which 221 potential participants were excluded (90 did not meet inclusion criteria, 84 declined to participate and 47 were unable to contact family). This meant 224 participants were enrolled and randomly assigned (1 : 1) to either the ERP BT group (n = 112) or psychoeducation group (n = 112). The characteristics of the two groups were similar at baseline. The enrolled patients were mostly male (n = 177; 79%) and of white ethnicity (n = 195; 87%). Only 13% of participants were receiving tic medication. Adherence to the intervention was good in 99 (88%) of the 112 participants in the ERP group, and 105 (94%) of the 112 participants in the psychoeducation group were classified as treatment completers (i.e. completing at least the first four chapters). Retention to the primary outcome at the 3-month primary end point (90%) and 6-month follow-up (> 80%) was excellent. Retention to the primary outcome measure remained high at 12 months (81% in both arms) and 18 months (> 79% in both arms). The primary analysis showed that participants in the ERP group [16% reduction, standard deviation (SD) 1.1] had a greater decrease in tics than those in the psychoeducation group (6% reduction, SD 1.0) at 3 months (primary end point). The estimated mean difference in YGTSS-TTSS change between the groups adjusted for baseline and site was −2.29 points [95% confidence interval (CI) −3.86 to −0.71] in favour of ERP, with an effect size of −0.31 (95% CI −0.52 to −0.10). This effect was sustained at 6 months, with a mean decrease of 6.9 points (24%, SD 1.2) in the ERP group versus 3.4 points (12%, SD 1.0) in the psychoeducation group. For phase 2, participants in the ERP group continued to have a greater decrease in tics than the control group. The estimated mean difference in YGTSS-TTSS between groups adjusting for baseline and site at 12 months was −2.64 points (95% CI −4.48 to −0.79), with an effect size of −0.36 (95% CI −0.61 to −0.11), at 18 months it was −2.01 points (95% CI −3.86 to −0.15), with an effect size of −0.27 (95% CI −0.52 to −0.02), in favour of the ERP group. In addition, extended follow-up showed those receiving online ERP compared with online psychoeducation had reduced scores for low mood and anxiety at 12 and 18 months and superior tic-specific quality of life, with the largest effects seen at 18 months. The direct cost of the intervention was £155 per person, including £104.57 for the online platform, supervision and training and a mean variable cost of £50.43 per participant for therapist time in the trial. At 18 months, using proxy parent-completed CHU9D responses, there were a mean additional 0.040 (95% CI −0.004 to 0.083) quality-adjusted life-years (QALYs) per participant in the ERP group compared with psychoeducation, with an addition mean cost per participant of £662 (95% CI −£59 to £1384). The incremental cost-effectiveness ratio in the primary analysis was £16,708 per QALY gained from a health and social care cost perspective at 18 months. In the 10-year long-term decision model, online ERP cost £537 less per participant than face-to-face BT and resulted in 0.02 fewer QALYs. Two serious adverse events (SAEs) occurred (hospital attendance due to one ‘collapse’ and one ‘tic attack’), both in the active control psychoeducation group, neither of which were related to the study intervention. The process evaluation found that the ERP intervention was implemented with high fidelity, and participants found the intervention acceptable and satisfactory. Engagement was high, with child participants completing an average of 7.5/10 chapters and 99/112 (88.4%) participants completing the minimum of the first four chapters (the predefined threshold for effective dose). Parental engagement was the only significant independent predictor of child engagement. Improvement in tic severity and overall clinical condition was not moderated by the relationship between demographic or baseline clinical factors and engagement and no mediators were found. However, level of parental engagement was associated with overall clinical improvement, and this relationship was illuminated by the qualitative data. Conclusion Implications for health care The findings demonstrate that online, therapist-supported ERP for young people with chronic tic disorders is clinically effective at reducing tic severity. Therefore, this is an efficient public mental health approach to supporting young people with tics. The intervention can be delivered at lower cost than standard face-to-face BT and may also result in improved service efficiencies, allowing a greater number of young people to access evidence-based care. Future research implications Further ‘field trials’ should be conducted to explore the clinical and service implications of delivering the intervention in real-world settings. Given that online interventions are context dependent, exploring the validity of these findings in different cultures/countries is important. Future research should explore where online, therapist-supported ERP best fits in the tic disorder care pathway and how online and face-to-face therapy can be best combined (e.g. non-responders to online ERP are ‘stepped up’ to face-to-face therapy). Trial registrations This trial is registered as ISRCTN70758207 and ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.

Purpose Depression and anxiety afflict millions worldwide causing considerable disability. MULTI-PSYCH is a longitudinal cohort of genotyped and phenotyped individuals with depression or anxiety disorders who have undergone highly structured internet-based cognitive-behaviour therapy (ICBT). The overarching purpose of MULTI-PSYCH is to improve risk stratification, outcome prediction and secondary preventive interventions. MULTI-PSYCH is a precision medicine initiative that combines clinical, genetic and nationwide register data.Participants MULTI-PSYCH includes 2668 clinically well-characterised adults with major depressive disorder (MDD) (n=1300), social anxiety disorder (n=640) or panic disorder (n=728) assessed before, during and after 12 weeks of ICBT at the internet psychiatry clinic in Stockholm, Sweden. All patients have been blood sampled and genotyped. Clinical and genetic data have been linked to several Swedish registers containing a wide range of variables from patient birth up to 10 years after the end of ICBT. These variable types include perinatal complications, school grades, psychiatric and somatic comorbidity, dispensed medications, medical interventions and diagnoses, healthcare and social benefits, demographics, income and more. Long-term follow-up data will be collected through 2029.Findings to date Initial uses of MULTI-PSYCH include the discovery of an association between PRS for autism spectrum disorder and response to ICBT, the development of a machine learning model for baseline prediction of remission status after ICBT in MDD and data contributions to genome wide association studies for ICBT outcome. Other projects have been launched or are in the planning phase.Future plans The MULTI-PSYCH cohort provides a unique infrastructure to study not only predictors or short-term treatment outcomes, but also longer term medical and socioeconomic outcomes in patients treated with ICBT for depression or anxiety. MULTI-PSYCH is well positioned for research collaboration.

Abstract Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26–48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a “gene discovery zone”. To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.

Abstract This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18–75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008–2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.

Long-term follow-up data from trials of digital mental health interventions are rare. This study reports 2-year follow-up data from a non-inferiority trial (N = 152) comparing stepped-care (internet-delivered cognitive behavioral therapy [CBT] followed by traditional in-person CBT if needed) vs in-person CBT for pediatric obsessive-compulsive disorder. Both treatment groups had comparable long-term effects, with the majority of participants being responders (stepped-care 66 %; in-person CBT 71 %) 2 years after the end of treatment.

Objectives: Therapist-guided internet-delivered cognitive behaviour therapy (ICBT) is an efficacious treatment for obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD), but it is unclear if the results obtained in controlled trials can be reproduced in clinical settings. We evaluated the implementation of ICBT for OCD (OCD-NET) and BDD (BDD-NET) in the Swedish public health system. Methods: Consecutive referrals to an outpatient psychiatric clinic providing ICBT, with a primary diagnosis of OCD or BDD, were included in the study. Four hundred and thirty-four participants started OCD-NET and 163 started BDD-NET. The primary outcome measures were the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Y-BOCS for BDD (BDD-YBOCS), respectively. Participants were assessed before treatment, weekly during treatment, and after treatment. The study used the RE-AIM implementation framework, and the elements of reach, effectiveness, adoption, and implementation for the evaluation. Results: Intention to treat analysis of the OCD-NET sample (n = 434) showed a significant decrease in OCD symptoms from pre-treatment to post-treatment (mean reduction = −8.77 [95 % CI -9.48 to −8.05] p

Objectives: To evaluate the cost-effectiveness of internet-delivered cognitive behaviour therapy for body dysmorphic disorder (BDD-NET). Design: Secondary cost-effectiveness analysis from a randomised controlled trial on BDD-NET versus online supportive psychotherapy. Setting: Academic medical center. Participants: Self-referred adult participants with a primary diagnosis of body dysmorphic disorder and a score of 20 or higher on the modified Yale-Brown Obsessive Compulsive Scale for BDD (n = 94). Patients receiving concurrent psychotropic drug treatment were included if the dose had been stable for at least two months. Interventions: Participants received either BDD-NET (n = 47) or online supportive psychotherapy (n = 47) for 12 weeks. Primary and secondary outcome measures: The primary outcome measures were cost-effectiveness and cost-utility from a societal perspective, using remission status from a diagnostic interview and quality-adjusted life years (QALY), respectively. Secondary outcome measures were cost-effectiveness and cost-utility from a health care perspective and the clinic's perspective. Results: Compared to supportive psychotherapy, BDD-NET produced one additional remission for an average societal cost of $4132. The cost-utility analysis showed that BDD-NET generated one QALY to an average cost of $14,319 from a societal perspective. Conclusions: BDD-NET is a cost-effective treatment for body dysmorphic disorder, compared to online supportive psychotherapy. The efficacy and cost-effectiveness of BDD-NET should next be directly compared to in-person cognitive behaviour therapy. Trial registration: NCT02010619.

Abstract Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (

Objective Access to effective treatments for adolescents with depression needs to improve. Few studies have evaluated behavioural activation (BA) for adolescent depression, and none remotely delivered BA. This study explored the feasibility and acceptability of therapist-guided and self-guided internet-delivered BA (I-BA) in preparation for a future randomised controlled trial (RCT).Design A single-blinded randomised controlled feasibility trial.Setting A specialist outpatient clinic in Sweden.Participants Thirty-two adolescents with mild-to-moderate major depression, aged 13–17 years.Interventions Ten weeks of therapist-guided I-BA or self-guided I-BA, or treatment as usual (TAU). Both versions of I-BA included parental support. TAU included referral to usual care within child and youth psychiatry or primary care.Outcomes Feasibility measures included study take-up, participant retention, acceptability, safety and satisfaction. The primary outcome measure was the blinded assessor-rated Children’s Depression Rating Scale, Revised. The primary endpoint was the 3-month follow-up.Results 154 adolescents were screened and 32 were randomised to therapist-guided I-BA (n=11), self-guided I-BA (n=10) or TAU (n=11). Participant retention was acceptable, with two drop-outs in TAU. Most participants in TAU had been offered interventions by the primary endpoint. The mean number of completed chapters (total of 8) for adolescents was 7.5 in therapist-guided I-BA and 5.4 in self-guided I-BA. No serious adverse events were recorded. Satisfaction was acceptable in both I-BA groups. Following an intent-to-treat approach, the linear mixed-effects model revealed that both therapist-guided and self-guided I-BA (Cohen’s d=2.43 and 2.23, respectively), but not TAU (Cohen’s d=0.95), showed statistically significant changes on the primary outcome measure with large within-group effect sizes.Conclusions Both therapist-guided and self-guided I-BA are acceptable and potentially efficacious treatments for adolescents with depression. It is feasible to conduct a large-scale RCT to establish the efficacy and cost-effectiveness of I-BA versus TAU.Trial registration number ClinicalTrials.gov Registry (NCT04117789).

Abstract Background It is unclear how to best measure the complex symptom presentation of pediatric acute-onset neuropsychiatric syndrome (PANS). Methods Well-characterized participants of a 2–5 year follow-up study (n = 34; 56% male) underwent clinical evaluations and completed scales assessing global symptom severity, functional impairment and specific psychiatric symptoms. We explored inter-correlations between the measures and used intraclass correlation coefficients to evaluate the agreement between clinician-, parent- and child ratings of the same constructs. Results Ratings on symptom-specific measures varied largely between participants. Agreement between informants was excellent on functional scales, fair-to-moderate on global severity scales and mixed on symptom-specific scales. Clinician-rated global and functional measures had stronger inter-correlations with parent- and child-rated functional measures than with symptom-specific measures. Conclusions General instruments assessing global severity and functioning are well suited for the assessment and follow-up of PANS, but should be complemented by symptom-specific scales representative of core symptoms.

Abstract Background Treatment guidelines recommend behaviour therapy (BT) for patients with Tourette syndrome (TS) and chronic tic disorder (CTD). However, BT is rarely accessible due to limited availability of trained therapists and long travel distances to specialist clinics. Internet-delivered BT has the potential of overcoming these barriers through remote delivery of treatment with minimal therapist support. In the current protocol, we outline the design and methods of a randomised controlled trial (RCT) evaluating an internet-delivered BT programme referred to as BIP TIC. The trial’s primary objective is to determine the clinical efficacy of BIP TIC for reducing tic severity in young people with TS/CTD, compared with an active control intervention. Secondary objectives are to investigate the 12-month durability of the treatment effects and to perform a health economic evaluation of the intervention. Methods In this single-blind superiority RCT, 220 participants (9–17 years) with TS/CTD throughout Sweden will be randomised to 10–12 weeks of either therapist-supported internet-delivered BT based on exposure with response prevention (BIP TIC) or therapist-supported internet-delivered education. Data will be collected at baseline, 3 and 5 weeks into the treatment, at post-treatment, and 3, 6, and 12 months post-treatment. The primary endpoint is the 3-month follow-up. The primary outcome is tic severity as measured by the Yale Global Tic Severity Scale – Total Tic Severity Score. Treatment response is operationalised as scores of “Very much improved” or “Much improved” on the Clinical Global Impression – Improvement scale, administered at the primary endpoint. Outcome assessors will be blind to treatment condition at all assessment points. A health economic evaluation of BIP TIC will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up). There are no planned interim analyses. Discussion Participant recruitment started on 26 April 2019 and finished on 9 April 2021. The total number of included participants was 221. The final participant is expected to reach the primary endpoint in September 2021 and the 12-month follow-up in June 2022. Data analysis for the primary objective will commence after the last participant reaches the primary endpoint. Trial registration ClinicalTrials.gov NCT03916055 . Registered on 16 April 2019.

Abstract Objective Neuroimaging studies of obsessive‐compulsive disorder (OCD) patients have highlighted the important role of deep gray matter structures. Less work has however focused on subcortical shape in OCD patients. Methods Here we pooled brain MRI scans from 412 OCD patients and 368 controls to perform a meta‐analysis utilizing the ENIGMA‐Shape protocol. In addition, we investigated modulating effects of medication status, comorbid anxiety or depression, and disease duration on subcortical shape. Results There was no significant difference in shape thickness or surface area between OCD patients and healthy controls. For the subgroup analyses, OCD patients with comorbid depression or anxiety had lower thickness of the hippocampus and caudate nucleus and higher thickness of the putamen and pallidum compared to controls. OCD patients with comorbid depression had lower shape surface area in the thalamus, caudate nucleus, putamen, hippocampus, and nucleus accumbens and higher shape surface area in the pallidum. OCD patients with comorbid anxiety had lower shape surface area in the putamen and the left caudate nucleus and higher shape surface area in the pallidum and the right caudate nucleus. Further, OCD patients on medication had lower shape thickness of the putamen, thalamus, and hippocampus and higher thickness of the pallidum and caudate nucleus, as well as lower shape surface area in the hippocampus and amygdala and higher surface area in the putamen, pallidum, and caudate nucleus compared to controls. There were no significant differences between OCD patients without co‐morbid anxiety and/or depression and healthy controls on shape measures. In addition, there were also no significant differences between OCD patients not using medication and healthy controls. Conclusions The findings here are partly consistent with prior work on brain volumes in OCD, insofar as they emphasize that alterations in subcortical brain morphology are associated with comorbidity and medication status. Further work is needed to understand the biological processes contributing to subcortical shape.

Abstract Background Despite being the gold standard of research to determine effectiveness, randomised controlled trials (RCTs) often struggle with participant recruitment, engagement and retention. These issues may be exacerbated when recruiting vulnerable populations, such as participants with mental health issues. We aimed to update understanding of the scope of these problems in trials of health technology and identify possible solutions through reflecting on experiences from an exemplar trial (Online Remote Behavioural Intervention for Tics; ORBIT). Method We extracted anonymised data on recruitment, retention and requests for more funding and time from trials funded by the largest funder of health technology trials in the UK (the National Institute of Health Research Health Technology Assessment) between 2010 and 2020, and compared these with data from a recent, successful trial (ORBIT). ORBIT aimed to assess the clinical- and cost-effectiveness of blended online and human behavioural therapy for tics in young people. Many of the trial procedures, including recruitment, the intervention and data collection, were undertaken online. Results Data were extracted on 51 trials conducted between 2010 and 2020. Sixty per cent of trials failed to reach their original recruitment target and only 44% achieved their follow-up in the specified time frame. In contrast, ORBIT recruited to target and achieved 90% follow-up. We posit that these achievements are related to (a) judicious use of digital technology for trial procedures and (b) adequate numbers of highly trained and motivated trial staff. We provide details of both these to help other research teams plan and cost for successful trials. Conclusion An approach combining human and online methods may be advantageous in facilitating trial delivery, particularly in paediatric mental health services. Given the importance of successful clinical trials in advancing healthcare delivery and the waste of human and economic resources associated with unsuccessfully delivered trials, it is imperative that trials are appropriately costed and future research focusses on improving trial design and delivery. Trial registration The ORBIT trial is registered with ISRTCN ( ISRCTN70758207 ) Registered on March 20, 2018. and ClinicalTrials.gov ( NCT03483493 ). Registered on March 30, 2018.

Obsessive-compulsive disorder (OCD) is a treatable condition that often requires specialist care, particularly when comorbid with autism spectrum disorder (ASD). However, specialist clinics are few and typically located in large medical centers. To increase availability of evidence-based treatment for OCD in individuals with ASD, we adapted an internet-delivered cognitive behavior therapy (ICBT) protocol to suit the needs of these individuals and conducted a feasibility study (N = 22). The primary outcome was the clinician-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), administered at pre- and post-treatment as well as 3 months after treatment. ICBT was deemed acceptable and was associated with clinically significant improvements in CY-BOCS scores, corresponding to a large within-group effect size (Cohen's d = 1.33). Similarly, significant improvements were observed in most of the secondary parent- and self-rated measures. Approximately 60% of the participants were classed as treatment responders and 50% were in remission from their OCD at the 3-month follow-up. To provide a meaningful benchmark, we also analyzed data from a specialist clinic that regularly treats individuals with comorbid OCD and ASD (N = 52). These analyses indicated that specialized in-person CBT produced significantly larger effects (d = 2.69) while being markedly more resource demanding, compared to ICBT. To conclude, ICBT can be successfully adapted to treat OCD in youth with ASD and may be a viable alternative for those who do not have direct access to highly specialized treatment. Further improvements of the treatment protocol based on participant and therapist feedback are warranted, as is a formal test of its efficacy and cost-effectiveness in a randomized controlled trial.

Abstract Cognitive behavior therapy (CBT) is the recommended first-line intervention for children and adolescents with obsessive-compulsive disorder (OCD), but is not broadly accessible. Internet-delivered CBT (ICBT) with minimal therapist support is efficacious and cost-effective, at least in the short term. Whether the therapeutic gains of ICBT for OCD are sustained in the long run is unknown. In this study, 61 adolescents with OCD who participated in a randomized trial of ICBT were followed-up 3 and 12 months after treatment. The proportion of treatment responders and remitters remained stable from post-treatment to 3-month follow-up and increased significantly from 3-month to 12-month follow-up. This study suggests that the gains of ICBT for youth with OCD are not only maintained long-term, but that further improvements continue to occur during follow-up.

Abstract Background Previous attempts to identify predictors of treatment outcomes in body dysmorphic disorder (BDD) have yielded inconsistent findings. One way to increase precision and clinical utility could be to use machine learning methods, which can incorporate multiple non-linear associations in prediction models. Methods This study used a random forests machine learning approach to test if it is possible to reliably predict remission from BDD in a sample of 88 individuals that had received internet-delivered cognitive behavioral therapy for BDD. The random forest models were compared to traditional logistic regression analyses. Results Random forests correctly identified 78% of participants as remitters or non-remitters at post-treatment. The accuracy of prediction was lower in subsequent follow-ups (68, 66 and 61% correctly classified at 3-, 12- and 24-month follow-ups, respectively). Depressive symptoms, treatment credibility, working alliance, and initial severity of BDD were among the most important predictors at the beginning of treatment. By contrast, the logistic regression models did not identify consistent and strong predictors of remission from BDD. Conclusions The results provide initial support for the clinical utility of machine learning approaches in the prediction of outcomes of patients with BDD. Trial registration ClinicalTrials.gov ID: NCT02010619 .

Abstract Background Population-based administrative registers are often used for research purposes. However, their potential usefulness depends on the validity of the registered information. This study assessed the validity of the recorded codes for social anxiety disorder (SAD), also known as social phobia, in the Swedish National Patient Register (NPR). Methods The personal identification numbers of 300 randomly selected individuals with a diagnosis of SAD recorded in the NPR were obtained from the Swedish National Board of Health and Welfare. The medical files of these individuals were then requested from clinics nationally. A total of 117 files were received and two independent raters reviewed each file to assess the presence or absence of SAD, according to the definition of the International Classification of Diseases, Tenth Edition (ICD-10) and the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). When disagreements between the two raters were found, a third rater reviewed the file to establish a best estimate diagnosis. Positive predictive values (PPV) and agreement between the two initial raters (using Cohen’s kappa) were calculated. Additionally, raters completed the Clinical Global Impression – Severity (CGI-S) and the Global Assessment of Functioning (GAF) rating scales for each file. Inter-rater agreement for the CGI-S and the GAF was assessed using intraclass correlation coefficients (ICC). Results After exclusion of files not containing sufficient information, 95 files were included in the analyses. Of these, 77 files (81.05%) were considered to be ‘true positive’ cases (PPV = 0.81, 95% confidence interval = 0.72–0.88). Inter-rater agreement regarding the presence or absence of SAD was substantial (κ = 0.72). CGI-S and GAF scores indicated that patients were in the moderate range of severity and functional impairment. Inter-rater agreement for the CGI-S and the GAF was moderate to good (ICC = 0.72 and ICC = 0.82, respectively). Conclusions The ICD-10 codes for SAD in the Swedish NPR are generally valid and reliable, but we recommend sensitivity analyses in future register-based studies to minimise the impact of potential diagnostic misclassification. Most patients were moderately severe and impaired, suggesting that results from register-based studies of SAD may be generalizable.

Abstract Background Obsessive-compulsive disorder (OCD) is a clinically heterogeneous disorder. Currently, the Obsessive Compulsive Inventory-Child Version (OCI-CV) is the only self-report measure that fully captures this symptom heterogeneity in children and adolescents. The psychometric properties of the OCI-CV are promising but evaluations in large clinical samples are few. Further, no studies have examined whether the measure is valid in both younger and older children with OCD and whether scores on the measure are elevated in youths with OCD compared to youths with other mental disorders. Methods To address these gaps in the literature, we investigated the psychometric properties and validity of a Swedish version of the OCI-CV in a large clinical sample of youth aged 6–18 years with OCD (n = 434), anxiety disorders (n = 84), and chronic tic disorders (n = 45). Results Internal consistency coefficients at the total scale and subscale level were consistent with the English original and in the acceptable range. Confirmatory factor analyses revealed an adequate fit for the original six-factor structure in both younger and older children with OCD. Correlations between total scores on the OCI-CV and the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were small at pre-treatment (r = 0.19) but large at post-treatment (r = 0.62). Youth with OCD scored higher than those with anxiety and chronic tic disorders, and the OCI-CV was sensitive to symptom change for youth undergoing treatment for OCD. Conclusions This Swedish version of the OCI-CV appears to be a valid and reliable measure of the OCD symptom dimensions across age groups and has good clinical utility.

BackgroundIn mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information.ObjectivesWe describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities.MethodsThe novel approach consists of a modification of Seed-based d Mapping—with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults.DiscussionThe novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools.

Objectives There is concern that the COVID-19 pandemic will be associated with an increase in suicides, but evidence supporting a link between pandemics and suicide is limited. Using data from the three influenza pandemics of the 20th century, we aimed to investigate whether an association exists between influenza deaths and suicide deaths.Design Time series analysis.Setting Sweden.Participants Deaths from influenza and suicides extracted from the Statistical Yearbook of Sweden for 1910–1978, covering three pandemics (the Spanish influenza, the Asian influenza and the Hong Kong influenza).Main outcome measures Annual suicide rates in Sweden among the whole population, men and women. Non-linear autoregressive distributed lag models was implemented to explore if there is a short-term and/or long-term relationship of increases and decreases in influenza death rates with suicide rates during 1910–1978.Results Between 1910 and 1978, there was no evidence of either short-term or long-term significant associations between influenza death rates and changes in suicides (β coefficients of 0.00002, p=0.931 and β=0.00103, p=0.764 for short-term relationship of increases and decreases in influenza death rates, respectively, with suicide rates, and β=−0.0002, p=0.998 and β=0.00211, p=0.962 for long-term relationship of increases and decreases in influenza death rates, respectively, with suicide rates). The same pattern emerged in separate analyses for men and women.Conclusions We found no evidence of short-term or long-term association between influenza death rates and suicide death rates across three 20th century pandemics.

BackgroundThe Online Remote Behavioral Intervention for Tics (ORBIT) study was a multicenter randomized controlled trial of a complex intervention that consisted of a web-based behavioral intervention for children and young people with tic disorders. In the first part of a two-stage process evaluation, we conducted a mixed methods study exploring the reach, dose, and fidelity of the intervention and contextual factors influencing engagement. ObjectiveThis study aims to explore the fidelity of delivery and contextual factors underpinning the ORBIT trial. MethodsBaseline study data and intervention usage metrics from participants in the intervention arm were used as quantitative implementation data (N=112). The experiences of being in the intervention were explored through semistructured interviews with children (n=20) and parent participants (n=20), therapists (n=4), and referring clinicians (n=6). A principal component analysis was used to create a comprehensive, composite measure of children and young people’s engagement with the intervention. Engagement factor scores reflected relative uptake as assessed by a range of usage indices, including chapters accessed, number of pages visited, and number of log-ins. The engagement factor score was used as the dependent variable in a multiple linear regression analysis with various contextual variables as independent variables to assess if there were any significant predictors of engagement. ResultsThe intervention was implemented with high fidelity, and participants deemed the intervention acceptable and satisfactory. The engagement was high, with child participants completing an average of 7.5 of 10 (SD 2.7) chapters, and 88.4% (99/112) of participants completed the minimum of the first four chapters—the predefined threshold effective dose. Compared with the total population of children with tic disorders, participants in the sample tended to have more educated parents and lived in more economically advantaged areas; however, socioeconomic factors were not related to engagement factor scores. Factors associated with higher engagement factor scores included participants enrolled at the London site versus the Nottingham site (P=.01), self-referred versus clinic referred (P=.04), higher parental engagement as evidenced by the number of parental chapters completed (n=111; ρ=0.73; P

Obsessive-compulsive disorder (OCD) can be successfully treated with cognitive behaviour therapy (CBT). However, as few patients have access to CBT, there is a strong push to develop and evaluate scalable and cost-effective internet-delivered interventions. BIP OCD is a therapist-guided online CBT intervention for pediatric OCD that has shown promise in trials conducted at a single site in Stockholm, Sweden. In this study, we evaluated if BIP OCD is an acceptable, feasible, and effective treatment in other countries and clinical contexts. Thirty-one patients were recruited at three different sites; a specialist OCD clinic in Gothenburg (Sweden), a specialist OCD clinic in London (United Kingdom), and a university-based clinic in Brisbane (Australia). Acceptability and feasibility measures included treatment adherence and feedback from therapists. Clinician assessments were conducted at baseline, post-treatment, and 3-month follow-up. The average module completion for the participants was 8.1/12 (SD=3.2) and the majority of patients completed the BIP OCD treatment (100% in Gothenburg, and 55.6% in both London and Brisbane). Pooling data from the three sites, the within-group effect sizes from baseline to post-treatment on the Children's Yale-Brown Obsessive-Compulsive Scale were in the expected range (bootstrapped Cohen's d=1.78; 95% CI 1.18–2.39), with an additional symptom reduction to the 3-month follow-up (bootstrapped Cohen's d=0.27; 95% CI 0.02–0.51). Participating therapists identified both advantages and difficulties supporting patients in this digital format. The results of this study suggest that the treatment effects obtained in the original BIP OCD trials can be generalized to other clinical contexts nationally and internationally. Lessons learned provide important information for successful implementation of BIP OCD in regular healthcare contexts.

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

BackgroundInternet-delivered cognitive behavioural therapy (ICBT) is a promising approach for increasing access to evidence-based treatments.AimsTo develop and evaluate the feasibility and preliminary efficacy of an ICBT programme for young children with obsessive–compulsive disorder (OCD), named BIP OCD Junior.MethodEleven 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).ResultsThere 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.ConclusionsBIP 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.Declaration of interestNone.

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share problems with sustained attention, and are proposed to share deficits in switching between default mode and task positive networks. The aim of this study was to investigate shared and disorder-specific brain activation abnormalities during sustained attention in the two disorders. Twenty boys with ADHD, 20 boys with OCD and 20 age-matched healthy controls aged between 12 and 18years completed a functional magnetic resonance imaging (fMRI) version of a parametrically modulated sustained attention task with a progressively increasing sustained attention load. Performance and brain activation were compared between groups. Only ADHD patients were impaired in performance. Group by sustained attention load interaction effects showed that OCD patients had disorder-specific middle anterior cingulate underactivation relative to controls and ADHD patients, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus (IFG). ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network relative to controls, but had disorder-specific overactivation in anterior default mode regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. In sum, ADHD and OCD patients showed mostly disorder-specific patterns of brain abnormalities in both task positive salience/ventral attention networks with lateral frontal deficits in ADHD and middle ACC deficits in OCD, as well as in their deactivation patterns in medial frontal DMN regions. The findings suggest that attention performance in the two disorders is underpinned by disorder-specific activation patterns. Keywords: ADHD, DMN, fMRI, OCD, Vigilance

BackgroundTelephone cognitive–behaviour therapy (TCBT) may be a cost-effective method for improving access to evidence-based treatment for obsessive–compulsive disorder (OCD) in young people.AimsEconomic evaluation of TCBT compared with face-to-face CBT for OCD in young people.MethodRandomised non-inferiority trial comparing TCBT with face-to-face CBT for 72 young people (aged 11 to 18) with a diagnosis of OCD. Cost-effectiveness at 12-month follow-up was explored in terms of the primary clinical outcome (Children's Yale-Brown Obsessive-Compulsive Scale, CY-BOCS) and quality-adjusted life-years (QALYs) (trial registration: ISRCTN27070832).ResultsTotal health and social care costs were higher for face-to-face CBT (mean total cost £2965, s.d. = £1548) than TCBT (mean total cost £2475, s.d. = £1024) but this difference was non-significant (P = 0.118). There were no significant between-group differences in QALYs or the CY-BOCS and there was strong evidence to support the clinical non-inferiority of TCBT. Cost-effectiveness analysis suggests a 74% probability that face-to-face CBT is cost-effective compared with TCBT in terms of QALYs, but the result was less clear in terms of CY-BOCS, with TCBT being the preferred option at low levels of willingness to pay and the probability of either intervention being cost-effective at higher levels of willingness to pay being around 50%.ConclusionsAlthough cost-effectiveness of TCBT was sensitive to the outcome measure used, TCBT should be considered a clinically non-inferior alternative when access to standard clinic-based CBT is limited, or when patient preference is expressed.Declaration of interestD.M.-C. reports research grants from the Swedish Research Council (Vetenskapsrådet), the Swedish Research Council for Health, working life and welfare (Forte), the US National Institute of Mental Health (NIMH), the UK National Institute of Health Research (NIHR), as well as royalties from Wolters Kluwer Health and Elsevier, all unrelated to the submitted work.

Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses.Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods.Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models.Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.

BACKGROUND: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. METHODS AND FINDINGS: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 ( 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. CONCLUSIONS: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.

Twin studies of hoarding symptoms indicate low to moderate heritability during adolescence and considerably higher heritability in older samples, suggesting dynamic developmental etiological effects. The aim of the current study was to estimate the relative contribution of additive genetic and environmental effects to hoarding symptoms during adolescence and young adulthood and to estimate the sources of stability and change of hoarding symptoms during adolescence.Univariate model-fitting was conducted in three cohorts of twins aged 15 (n = 7,905), 18 (n = 2,495) and 20-28 (n = 6,218). Longitudinal analyses were conducted in a subsample of twins for which data on hoarding symptoms was available at both age 15 and 18 (n = 1,701).Heritability estimates for hoarding symptoms at ages 15, 18 and 20-28 were 41% (95% confidence interval [CI]: 36-45%), 31% (95% CI: 22-39%) and 29% (95% CI: 24-34%) respectively. Quantitative sex-differences emerged in twins aged 15 at which point the heritability in boys was 33% (95% CI: 22-41%) and 17% (95% CI: 0-36%) in girls. Shared environmental effects played a negligible role across all samples with the exception of girls aged 15 where they accounted for a significant proportion of the variance (22%; 95% CI 6-36%). The longitudinal bivariate analyses revealed a significant phenotypic correlation of hoarding symptoms between ages 15 and 18 (0.40; 95% CI: 0.36-0.44) and a strong but imperfect genetic correlation (0.75; 95% CI: 0.57-0.94). The bivariate heritability was estimated to 65% (95% CI: 50-79%).Hoarding symptoms are heritable from adolescence throughout young adulthood, although heritability appears to slightly decrease over time. Shared environmental effects contribute to hoarding symptoms only in girls at age 15. The stability of hoarding symptoms between ages 15 and 18 is largely explained by genetic factors, while non-shared environmental factors primarily have a time-specific effect. The findings indicate that dynamic developmental etiological effects may be operating across the life span.

Background: Obsessive-compulsive disorder (OCD) is increasingly being viewed as a multidimensional heterogeneous disorder caused due to the dysfunction of several closely related, overlapping frontostriatal circuits. A study investigating the dimensional construct in treatment naïve, co-morbidity free patients with identical handedness is likely to provide the necessary homogeneity and power to elicit neural correlates of the various symptom dimensions, and overcome the limitations of previous studies. Materials and Methods: Nine DSM-IV OCD patients with predominant contamination-related obsessive-compulsive symptoms (age=29.8±7.1 years; five males: four females; years-of-education=13.9±1.6, YBOCS total score=28.8±4.7, DYBOCS Contamination dimension score=10.7±1.8) and nine healthy controls matched one to one with the patients for age, sex, and years of education (age=27.8±5.4, five males: four females; years-of-education=14.9±3.0), were examined during symptom provocation task performance in 3TMRI. Paired samples t test of brain activation differences (contamination relevant pictures - neutral pictures), limited to apriori regions of interest was done using SPM8 (uncorrected P

Anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and obsessive-compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of 'ordering' symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.

BACKGROUND:International guidelines recommend Cognitive Behavior Therapy (CBT) as the first line treatment for pediatric obsessive-compulsive disorder (OCD). However, a substantial proportion of patients do not have access to such treatment. We developed and tested the feasibility, efficacy and acceptability of a novel therapist-guided, Internet-delivered CBT (ICBT) platform for adolescents with OCD. METHODS:An interactive, age-appropriate ICBT platform ("BiP OCD") was developed. Twenty-one adolescents (12-17 years) with a DSM-IV diagnosis of OCD and their parents were enrolled in the study. All participants received 12 weeks of ICBT with therapist support. The primary outcome measure was the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Acceptability was assessed at post-treatment. RESULTS:Participants completed on average 8.29 (SD = 3.0) of the 12 treatment chapters. Treatment yielded significant improvements on all clinician-, parent- and most self-administered outcome measures, with a large effect size of d = 2.29 (95% CI 1.5-3.07) on the CY-BOCS. Patients continued to improve at follow-up. At 6-month follow-up, 71% were classified as responders (≥35% decrease on the CY-BOCS) and 76% as being in remission (CY-BOCS score ≤12). Average clinician support time was less than 20 minutes per patient per week. The majority of participants felt that BiP OCD was age-appropriate and rated the treatment as good or very good. CONCLUSIONS:ICBT could be efficacious, acceptable, and cost-effective for adolescents with OCD. More rigorously controlled studies are needed to further evaluate the treatment. TRIAL REGISTRATION:ClinicalTrials.gov; NCT01809990.

BackgroundHoarding Disorder (HD) is often assumed to be an 'old age' problem, but many individuals diagnosed with HD retrospectively report first experiencing symptoms in childhood or adolescence. We examined the prevalence, comorbidity and etiology of hoarding symptoms in adolescence.MethodsTo determine the presence of clinically significant hoarding symptoms, a population-based sample of 15-year old twins (N = 3,974) completed the Hoarding Rating Scale-Self Report. Co-occurring Obsessive Compulsive Disorder (OCD), Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) were estimated from parental report. Model-fitting analyses divided hoarding symptom scores into additive genetic, shared, and non-shared environmental effects.ResultsThe prevalence of clinically significant hoarding symptoms was 2% (95% CI 1.6-2.5%), with a significantly higher prevalence in girls than boys. Exclusion of the clutter criterion (as adolescents do not have control over their environment) increased the prevalence rate to 3.7% (95% CI 3.1-4.3%). Excessive acquisition was reported by 30-40% among those with clinically significant hoarding symptoms. The prevalence of co-occurring OCD (2.9%), ASD (2.9%) and ADHD (10.0%) was comparable in hoarding and non-hoarding teenagers. Model-fitting analyses suggested that, in boys, additive genetic (32%; 95% CI 13-44%) and non-shared environmental effects accounted for most of the variance. In contrast, among girls, shared and non-shared environmental effects explained most of the variance, while additive genetic factors played a negligible role.ConclusionsHoarding symptoms are relatively prevalent in adolescents, particularly in girls, and cause distress and/or impairment. Hoarding was rarely associated with other common neurodevelopmental disorders, supporting its DSM-5 status as an independent diagnosis. The relative importance of genetic and shared environmental factors for hoarding differed across sexes. The findings are suggestive of dynamic developmental genetic and environmental effects operating from adolescence onto adulthood.