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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 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.

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.

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.