Abstract Background Fatigue is the main complaint of 5–10% of patients in primary care and is often associated with significant suffering and functional disability. Cognitive behavioral therapy (CBT) has demonstrated efficacy in reducing fatigue severity in diverse clinical populations in specialized healthcare settings, with common treatment mechanisms identified across conditions. This study is the first to evaluate the feasibility and acceptability of a transdiagnostic CBT (tCBT) for a heterogeneous sample of patients suffering from severe and persistent fatigue in a primary care context. Methods A single-arm feasibility study was conducted in routine primary care. Adults with severe and persistent fatigue received a blended tCBT combining individual sessions and internet-based materials. Feasibility and acceptability were evaluated through adherence, completion, attrition, therapist fidelity, patient satisfaction, credibility, and negative effects. Preliminary effectiveness was evaluated by self-reported symptom change from pre- to post-treatment (6 months). Results Eighteen participants were enrolled, of whom fourteen completed the full intervention. Treatment adherence and therapist fidelity were satisfactory, and data attrition was minimal. Participants reported high satisfaction and treatment credibility. No serious adverse events were reported. Half of the participants reported some negative effects of treatment, primarily consisting of transient increases in fatigue and sleep disturbances. Large within-group reductions were observed in self-reported fatigue severity and functional impairment over the 6-month treatment period. Conclusions Preliminary findings suggest that tCBT for fatigue is feasible and acceptable in a primary care setting. Interpretation is limited by the small sample size and single-arm design. Larger randomized controlled trials are warranted to evaluate effectiveness and to determine which patients benefit most and through which mechanisms. Trial registration Pre-registered on Clinicaltrials.gov (NCT06341751), registration date: 2024-03-13.

Purpose Psychiatric disorders are a leading cause of work disability and productivity loss. Internet-delivered cognitive behavioral therapy (ICBT) is effective for symptom reduction in common mental health disorders, yet long-term socioeconomic outcomes are rarely evaluated. We aimed to predict future labor market marginalization (LMM) in patients with depression and anxiety disorders and assess whether treatment-course variables and polygenic scores added predictive value. Methods We used clinical, register-based, treatment-course, and genetic data from a large clinical MULTI-PSYCH cohort ( n = 2630). LMM was defined as receipt of disability pension, sickness absence > 90 days, or unemployment > 180 days one year after ICBT. Elastic net-regularized logistic regression, random forest, and XGBoost models were trained using nested cross-validation and evaluated in a temporally separated holdout test set ( n = 525). Results All algorithms performed comparably and showed moderate discrimination (AUC test 0.754–0.768) but limited sensitivity (37–40%) and less reliable calibration in the highest predicted risk range. Inclusion of treatment-course predictors yielded only marginal improvement, while polygenic scores provided no incremental prognostic value. Most predictive signal for post-ICBT LMM was present before treatment and was dominated by cumulative burden of prior work disability, functional impairment, and long-term psychiatric morbidity. Conclusion Current models may support early risk stratification in patients treated with ICBT and provide a basis for future evaluation of adjunct work-promoting interventions.

Background Suicidal behaviour shows notable sex differences, and understanding whether genetic factors contribute to these differences is critical for identifying at-risk individuals and prevention.Objective We aim to investigate the genetic contribution to suicide attempts and examine whether genetics account for sex differences in incidence.Methods This population-based cohort study includes 3.1 million individuals born 1963–1998 and followed through Swedish National Registers, including hospitals and specialist outpatient diagnoses and cause of death data. Suicide attempts were identified using ICD codes, indicating intentional self-harm, self-harm using lethal methods or leading to hospitalisation, or resulting in death. Familial aggregation, coaggregation, pedigree heritability and genetic correlations were estimated using genealogical data. For sex-specific analyses, we examined mother–daughter, female sibling, father–son and male sibling pairs, separately.Findings Suicide attempts were more common among females than males (3.3% vs 2.6%). In both sexes, risk aggregated within families (ORs ranged 1.6–3.4 across relative types) and was higher in first-degree than second-degree relatives. Familial aggregation was stronger in females than in males, and in same-sex first degree relatives compared with cross-sex pairs. Pedigree heritability was 41.9% (95% CI 36.0 to 48.4%) and did not differ significantly by sex (female 51.4% (95% CI 40.1% to 58.6%), male 45.1% (95% CI 32.3% to 52.5%), Bootstrap p value 0.40). Suicide attempt showed moderate to high pedigree genetic correlations with psychiatric disorders, strongest with substance use disorders (SUD, rg=0.85 (95% CI 0.83 to 0.96)), with no significant sex differences. The genetic correlation between female and male suicide attempts was high (0.85 (95% CI 0.80 to 0.99)), suggesting a substantial genetic overlap.Conclusions Suicide attempt has a moderate heritable component that largely overlaps between females and males and with other psychiatric disorders, particularly SUD. Stronger familial aggregation in females and in same-sex pairs highlights the potential role of sex-specific environmental or social factors. Future research should focus on non-genetic contributors and their potential interaction with genetic factors to better understand and address sex disparities in suicidal behaviourClinical implications Genetic risk for suicide attempt is substantial but does not fully explain sex differences in incidence. Clinicians should, therefore, consider non-genetic, including sex-specific environmental and social factors, alongside family history and psychiatric comorbidity when assessing suicidal risk.

The causal link between potentially traumatic events and obsessive-compulsive disorder (OCD) remains unclear due to reliance on retrospective self-reports and limited control for familial factors. Here, in this Swedish population-based cohort study, we identified 3,340,945 individuals born between 1975 and 2008 and prospectively examined the associations of objectively recorded assault/victimization and transport accidents with subsequent OCD diagnoses. Individuals exposed to assault/victimization, but not transport accidents, had an increased OCD risk (hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.63-1.83), especially within the first year (HR 2.31, 95% CI 1.98-2.70), decreasing thereafter (HR 1.67, 95% CI 1.57-1.77). The association persisted in discordant full sibling comparisons (HR 1.37, 95% CI 1.23-1.54). Quantitative genetic modeling indicated that the phenotypic correlation (r = 0.12) was primarily due to additive genetic (69%) and unique environmental factors (31%). These findings highlight a complex relationship between assault/victimization and OCD, involving both genetic vulnerability and individual environmental exposure.

In epidemiological studies, obsessive-compulsive disorder (OCD) is robustly associated with increased risk of cardiometabolic disorders, including cardiovascular diseases, type 2 diabetes, and obesity. However, the mechanisms behind these associations are unclear. We conducted genetic correlation analyses to explore shared genetic etiology and bi-directional summary-level Mendelian randomization (MR) to explore potential causal effects between genetic liability to OCD and 14 cardiometabolic phenotypes (e.g., coronary artery disease, blood pressure, body mass index [BMI]). If causal effects were observed, we planned to conduct multivariable MR to explore indirect effects via health behaviors. We found no evidence for genetic correlations between OCD and any of the cardiometabolic phenotypes under study, except for a negative correlation with BMI (rG = -0.123, SE = 0.029, p < 0.001). Summary-level MR showed no evidence for causal effects. Therefore, multivariable MR was not conducted. We found limited evidence for shared genetic etiology or causal effects using the largest OCD GWAS to date. However, we were predominantly only powered to detect medium to large effects in the direction of OCD to cardiometabolic traits, leaving the possibility of smaller causal effects existing. Future studies with larger, more representative samples will help to further interpret findings.

Cognitive behavioral therapy (CBT) is a well-established, evidence-based treatment for common mental disorders such as depression, anxiety disorders, and obsessive-compulsive disorder (OCD). However, treatment outcomes vary widely, and a substantial proportion of patients do not achieve sufficient improvement. Robust predictors of individual differences in symptom change are currently lacking. Genetic differences have been suggested to play a role, but existing evidence is inconclusive. This study investigated the extent to which common genetic variants-single nucleotide polymorphisms (SNPs)-contribute to variability in symptom change. The sample was derived from the MULTI-PSYCH and NORDiC cohorts, comprising 3113 adults and children treated with CBT for depression, panic disorder, social anxiety disorder, or OCD. We performed a genome-wide association study (GWAS) of symptom change following CBT and estimated the proportion of variance attributed to SNPs. Secondary analyses included GWAS and SNP-based heritability estimation of additional clinically relevant outcomes: pre- and post-treatment symptom severity and remission status. No variants reached genome-wide significance. We estimated SNP-based heritability of symptom change at h SNP 2  = 0.221 (SE = 0.123). These results suggest that common genetic variation may contribute modestly to treatment outcomes. Much larger samples would be required to obtain more precise estimates and to detect genome-wide significant loci.

Background:Up to 50% of patients treated with internet-delivered cognitive behavioral therapy (ICBT) for depression and anxiety disorders do not experience clinically significant symptom reduction. Identifying these patients prior to the initiation of ICBT can support treatment planning. Objective:The aim of this study was to enhance baseline prediction of clinically meaningful improvement in patients treated with ICBT for common psychiatric disorders in routine care, which could ultimately inform treatment planning at intake. Methods:We developed multimodal predictive models integrating clinical, sociodemographic, and genetic data available pretreatment to predict clinically meaningful improvement in a sample of 1790 patients treated with ICBT for major depressive disorder, panic disorder, and social anxiety disorder. We applied machine learning algorithms of varying complexity (logistic regression, random forest [RF], extreme gradient boosting, support vector machines, soft voting, and stacking ensemble), with nested cross-validation, elastic net variable selection, multiple imputation, and temporal validation in a 20% holdout test set (n=356). The primary performance measure was the area under the receiver operating characteristic curve (AUC). Results:All full phenotypic models showed comparable performance (AUCtest 0.732-0.749), with RF achieving the best holdout discrimination (AUCtest 0.749, 95% CI 0.698-0.797). Compared with the benchmark model based on self-reported screening data (AUCtest 0.695, 95% CI 0.637-0.748), RF and both ensemble models incorporating register data showed higher discrimination in paired DeLong tests (P=.04, P=.02, and P=.03, respectively), whereas polygenic scores added no independent predictive value in this cohort and modeling setup (P=.97). Conclusions:These promising results support the feasibility of baseline prognostic prediction of clinically meaningful improvement after ICBT and provide a basis for the prospective validation of model-informed risk stratification.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by symptoms that emerge in childhood and often improve or even disappear in adulthood, providing a model for understanding how altered brain development shapes neural structure and function. We investigate brain structural alterations in TS and Chronic Tic Disorders (TS/CTD) across development, presenting the largest structural neuroimaging analysis for TS/CTD to date (1,803 individuals from the ENIGMA-TS Working Group), and integrating with large-scale genomewide association studies. Nonlinear age effects were observed in cortical thickness across development and in thalamic volume in children, indicating altered trajectories of brain maturation. Pediatric and adult TS/CTD showed distinct structural patterns, with widespread alterations in childhood and more focal changes in adulthood. Children also showed the most prominent effects highlighting the involvement of orbitofrontal cortex and putamen, alongside additional regions such as frontal and paralimbic areas. Genetic pleiotropy analyses identified overlap between TS/CTD-associated genetic effects on brain structure and neuroanatomical differences. Cross-disorder comparisons revealed correlations with ADHD and OCD and age-related patterns. These findings demonstrate altered neurodevelopmental trajectories in TS/CTD and implicate systems underlying inhibitory control and urge regulation.

Mechanical restraint, forced medication, and seclusion are coercive measures that may be used during involuntary psychiatric hospitalisation. However, the extent of their usage and application across patient groups is unclear, limiting efforts to ensure equitable psychiatric care. Aim. To describe the absolute and relative risk of mechanical restraint, forced medication, and seclusion across sociodemographic and clinical patient characteristics. Methods. We conducted a population-wide cohort study of all involuntary psychiatric hospitalisations in Stockholm, 2012-2023 (n=49 873), using linked population-wide Swedish register data. We estimated crude absolute and relative risk adjusted for sex, age, and calendar year (aRR) with generalized estimating equations. Results. Out of all hospitalisations, 12 592 (25%) included at least one of these coercive measures. Mechanical restraint, forced medication, and seclusion were used during 6015 (12%), 9491 (19%), and 5562 (11%) of the hospitalisations, respectively. Across sociodemographic patient characteristics, the highest risk of being subject to any coercive measure was observed during hospitalisation among 18–24-year-olds (aRR 1.32 [1.22-1.43] vs. 65+ years) and patients born outside of Europe (1.20 [1.13-1.27] vs. Swedish-born). The risk was also elevated when patients were female (1.09 [1.04-1.10] vs. male), had low income (1.15 [1.06-1.25] vs. high income), primary education (1.10 [1.02-1.19] vs. higher education), or were unmarried (1.15 [1.08-1.25] vs. married). Clinically, the highest risk of any coercive measure was observed during hospitalisation for bipolar disorder (1.57 [1.42-1.73]), drug-induced psychosis (1.46 [1.31-1.62]), and for the category “other psychiatric disorders” meaning diagnoses not commonly motivating involuntary care, such as ADHD or delirium (1.48 [1.33-1.64]), compared with hospitalisation for alcohol use disorder. The risk was also elevated when patients had a lifetime history of psychiatric hospitalisation (1.26 [1.20-1.33]) or intellectual disability (1.22 [1.10-1.34]), but lower when hospitalisation was preceded by recent self-harm (0.69 [0.62-0.76]). The risk of mechanical restraint specifically was most pronounced during hospitalisation for personality disorder, while the risk of forced medication and seclusion was highest during hospitalisation for bipolar disorder and psychotic conditions. Conclusions. Coercive measures appear concentrated in identifiable patient subgroups, including socially vulnerable groups such as people born outside of Europe and those with intellectual disability. Targeted prevention strategies may help ensure equitable and safe delivery of involuntary psychiatric care. The analytic plan was preregistered at the Open Science Framework (https://osf.io/8rpu4).

To evaluate the feasibility, acceptability, safety, preliminary efficacy, and preliminary maintenance of TICNET, an online therapist-guided exposure and response prevention (ERP) for adults with Tourette syndrome or chronic tic disorder (TS/CTD). Single-group, unmasked feasibility trial. A psychiatric outpatient clinic specialized in obsessive-compulsive and related disorders in Stockholm, Sweden. Adult participants with TS/CTD were recruited nationwide by means of self- and clinical referrals. The 10-week online, ERP-based, therapist-supported programme TICNET consisted of eight chapters provided on a secure platform. The RE-AIM framework (Reach, Efficacy, Adoption, Implementation, and Maintenance) was used to assess feasibility and acceptability. Safety was measured with an adverse events questionnaire. Preliminary intervention effects on tic severity were measured with the Yale Global Tic Severity Scale – Total Tic Severity subscale. Outcome measures were collected at pre- and post-treatment, as well as at the 3-, 6- and 12-month follow-up. Out of 73 screened participants, 31 met inclusion criteria, with the most common reason for exclusion being not fulfilling the diagnostic criteria for TS/CTD. The participants completed an average of 6.5 out of 8 treatment chapters and 90

Abstract Objectives Although obsessive-compulsive disorder (OCD) is strongly associated with a range of modifiable somatic health problems, little is known about how the disorder influences the adoption and maintenance of healthy lifestyle habits, as well as how it shapes patients' experiences of seeking and receiving general healthcare. Methods Sixteen individuals with OCD and cardiometabolic risk who participated in the piloting of a lifestyle intervention completed a semi-structured interview about the impact of OCD on their lifestyle habits and their experiences with general medical services. The interviews were analysed using reflexive thematic analysis. Results The analysis generated three main themes and one overarching theme. The main themes were: (1) Living with multiple barriers to engage in healthy behaviours; (2) Changes in lifestyle habits – challenging but possible; and (3) OCD is a roadblock in general medical care. The overarching theme was: (4) It is not just OCD. The themes reflected that the participants experienced both disorder-specific and general barriers when trying to implement healthy lifestyle behaviours. Changing lifestyle habits was regarded as difficult, but facilitators of change were also identified. Participants reported that OCD affected seeking and receiving healthcare for their somatic problems. OCD was generally viewed as only one of many elements that affected health and lifestyle. Conclusions Our results indicate the need for tailored support for this at-risk group to change and maintain healthy lifestyles, as well as a need of increasing knowledge of OCD among general medical care practitioners. Trial registration Not applicable. Clinical trial number Not applicable.

The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably represent differential expressions of a dysregulated threat-response system. Here, we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 out of the 58 associations replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.

Prolonged exposure (PE) is an established treatment for PTSD, but outcomes are often limited by dropout and delivery constraints. This study evaluated the feasibility, acceptability, and preliminary effectiveness of intensive-format PE (I-PE) delivered as a pragmatic intervention in a Swedish psychiatric outpatient setting. Thirty-three adults meeting the diagnostic criteria for PTSD were enrolled in a single-center, uncontrolled pragmatic feasibility trial embedded in routine outpatient care in Sweden. I-PE comprised five consecutive days of therapist-guided treatment, followed by three individual booster sessions at weeks 2, 4, and 8. The primary objectives were to assess feasibility through reach, retention, treatment adherence, satisfaction, and safety. Clinical outcomes included clinician-rated PTSD severity with the Clinician-Administered PTSD Scale for DSM-5 at baseline and 6-month follow-up; self-reported PTSD with the PTSD Checklist for DSM-5 at baseline, posttreatment, and 6-month follow-up; complex PTSD symptoms with the International Trauma Questionnaire at baseline and posttreatment; and depression with the Patient Health Questionnaire-9 and quality of life with the EuroQol 5-Dimension at baseline, posttreatment, and 6-month follow-up. Analyses were conducted using mixed-effects linear models under an intention-to-treat framework. I-PE proved both feasible and acceptable within routine care; 97

BACKGROUND:Body dysmorphic disorder (BDD) is a debilitating and understudied psychiatric condition of largely unknown etiology. Emerging evidence suggests that BDD may be a familial and heritable disorder, but family studies of diagnosed individuals and their biological relatives are yet to be conducted. METHODS:We identified 4,857,049 individuals born in Sweden between 1960 and 2008 with information on both biological parents who were living in Sweden in 1997. From this cohort, we identified clusters of full siblings, half siblings, and cousins and compared the risk of BDD among those with a relative diagnosed with BDD and those without. Previously validated ICD-10 diagnoses of BDD were identified through the Swedish National Patient Register. To estimate hazard ratios (HRs), we fitted a series of Cox regression models with time-varying exposures and attained age as the underlying time scale. Individuals were considered unexposed before their relative's BDD diagnosis and exposed thereafter. RESULTS:Relatives of individuals with BDD had a higher risk of BDD compared with relatives of individuals without BDD, with the highest risk observed in full siblings (HR, 16.2; 95% CI, 9.2-28.7), followed by half-siblings (HR, 7.8; 95% CI, 2.5-23.9) and cousins (HR, 2.8; 95% CI, 1.3-6.2), showing a gradient by degree of genetic relatedness. CONCLUSIONS:Our findings indicate that BDD is a familial disorder and suggest an important role for genetic factors.

BACKGROUND:Suicide is more common among males and in older age, but the understanding of sex-specific and age-specific risk indicators is limited. OBJECTIVE:To describe the sex-specific and age-specific prevalence of 25 suicide risk indicators in the year preceding suicide and estimate their associations with suicide. METHODS:Register-based population-nested case-control study in Sweden, 2009-2021, comprising 19 741 suicide cases and 197 296 general population controls matched by sex, age and county of residence. Death by suicide was collected from the cause of death register. 25 suicide risk indicators covering psychiatric history, somatic disorders, bereavement and sociodemographic factors in the previous year were collected from nationwide registers. Sex-specific and age-specific ORs of suicide for the presence/absence of each risk indicator in the prior year were estimated and complemented by risk differences. FINDINGS:Suicide cases were 70% male, 9% were aged 15-24 years, 29% 25-44 years, 36% 45-64 years and 26% 65+ years. In the year preceding suicide, the prevalence of most risk indicators was the lowest among males and people aged 65+ years. Most risk indicators also showed weaker 1-year associations with suicide in these groups. The median OR (IQR) of suicide across the 25 risk indicators was 14.6 (5.2, 29.1) in females versus 10.3 (4.3, 21.3) in males, and 17.4 (6.5, 28.9) in 24-44 year-olds versus 8.0 (3.6, 23.7) in people aged 65+years. Risk differences of suicide were larger in males across nearly all risk indicators. CONCLUSIONS:There was considerable heterogeneity across sex and age groups, both in the prevalence of risk indicators preceding suicide and in their associations with suicide. Risk indicators were generally less common and displayed weaker associations with suicide on the relative risk scale among males and older people. CLINICAL IMPLICATIONS:Suicides in males and older people may be harder to predict, as indicators are rarer. When males present with risk indicators, they generally have a higher absolute risk of suicide, making them important targets for prevention even when risk indicators do not cause suicide. Our findings underscore the importance of considering sex-specific and age-specific risk indicators for individualised suicide prediction and prevention.

Objective To provide a comprehensive analysis of initial suicide attempts, covering incidence, risk factors, outcomes, and healthcare use in the month before and the month after the attempts.Design Comprehensive analysis of the Swedish population that included three designs: a retrospective cohort study to investigate incidence and healthcare use, a nested case-control study to investigate risk factors, and a matched cohort study to examine subsequent suicide attempts and mortality.Setting Comprehensive Swedish national registers that include patient diagnoses from hospitals and specialist outpatient care, and cause of death information updated to the end of 2019.Participants 3.7 million people born in Sweden in 1963-98 and followed from age 10 to 57 years.Main outcome measure First lifetime suicide attempt identified in patient and death registers using ICD (international classification of diseases) codes for intentional self-harm, any self-harm with lethal methods or requiring hospital admission, or any self-harm resulting in death.Results The lifetime risk of an initial suicide attempt in the study population was 4.6%, with greater risk in females and highest risk between ages 18 and 24. One in 10 families in Sweden had at least one family member who attempted suicide. Overdose and poisoning were the most common methods. Previous psychiatric disorders, general medical diseases, and adverse life events were associated with increased risk of initial suicide attempt, while higher socioeconomic status was associated with decreased risk. People with an initial suicide attempt were at substantially increased risk of subsequent attempts (hazard ratio 23.4), death by suicide (16.4), and all cause mortality (7.3). At least 60% of those who made an initial suicide attempt had a healthcare contact in the month before the attempt.Conclusions This study provides comprehensive data on the incidence, risk factors, outcomes, and healthcare use of initial suicide attempts in the Swedish population, highlighting the need for systematic prevention efforts for people who have attempted suicide for the first time.

BACKGROUND:Individuals with intellectual disabilities (ID) are disproportionately exposed to several risk factors for suicidality. However, no meta-analysis has yet quantified the relative risk of suicide and self-harm, including suicide attempts, within this population. The aim of this project was to bring together and synthesise the research on suicidality among individuals with ID. METHODS:A systematic review and meta-analysis was carried out. Medline, Embase, Web of Science and PsycInfo were searched from inception through 4 August 2025. Observational studies with a quantitative design, evaluating the relative risk of suicide or self-harm, including suicide attempts, in individuals with and without ID, were included. Risk of bias was assessed using a shortened version of the Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) checklist. A random effects model was used to synthesise the results. RESULTS:Eleven primary studies were included in the review (n = 241 438). The level of ID severity was only presented in two articles. Compared to the general population, the pooled relative risk for death by suicide was 0.54 (95% CI 0.33 to 0.89, k = 6, I2 = 77%) and the relative risk for self-harm was 3.16, (95% CI 2.3 to 4.35, k = 6, I2 = 89%). CONCLUSION:The findings suggest that individuals with ID have an elevated risk of self-harm but a lower risk of dying by suicide compared to the general population. However, these results should be interpreted with caution due to the limited number of primary studies and substantial between-study heterogeneity. Further, separate analyses of mild versus moderate-to-profound ID are warranted.

IntroductionTourette syndrome (TS) and chronic motor or vocal tic disorder (CTD) are neurodevelopmental disorders associated with functional impairment and reduced quality of life. Behavioral therapy (BT) is an effective treatment, but lack of experienced practitioners makes it hard for patients to receive appropriate help. One approach to bridge the gap between demand and availability is to offer the treatment remotely over the internet with minimal support from a therapist.MethodsThis single-blind randomized controlled superiority trial including 110 participants will compare internet-delivered BT (I-BT) primarily consisting of exposure and response prevention (ERP) to a control condition consisting of internet-delivered general psychological support. The primary aim of the trial is to evaluate whether ERP-based I-BT is superior to the control condition in reducing TS/CTD symptoms. The primary outcome measure is the Yale Global Tic Severity Scale - Total Tic Severity score administered by blinded raters at primary endpoint 11 weeks after the treatment start. Secondary endpoints occur at week 23 and 14 months after the treatment start, and the secondary outcomes include tic-related impairment, rates of responders, self-rated tic severity, symptoms of depression, quality of life and cost-effectiveness. Data on dropout rates and adverse events is also collected.DiscussionThis is the first randomized controlled trial to evaluate therapist-guided ERP-based I-BT for adults with TS/CTD. The study has been approved by the Swedish Ethical Review Authority (EPM 2023-06541-01). The hypotheses were pre-registered before the start of the data collection. Results from all analyses will be reported according to the Consolidated Standards of Reporting Trials statement for non-pharmacological trials (CONSORT) and Consolidated Health Economic Evaluation Reporting Standards (CHEERS). The participants in the control condition will have the opportunity to receive I-BT after the data from the first follow-up is collected. The study will be published in open access and the results will be shared with service user organizations. At the moment of submission, the study has recruited 87 out of 110 planned participants and the recruitment is expected to be completed in February 2025.Trial registrationOpen Science Framework: https://osf.io/cq97b/ (uploaded 31/01/2024); Clinicaltrials.gov: NCT06271083 (submitted 14/02/2024).

Tourette Syndrome (TS) and Persistent Tic Disorder (PTD) are childhood-onset neuropsychiatric conditions with high heritability. Due to current sample size limitations, identifying TS/PTD risk genes has been challenging. This study addressed this issue by conducting a meta-analysis of microarray copy number variant (CNV) studies from three TS/PTD genomics consortia, supplemented with new data from 3,291 cases. This approach more than doubled the sample size of previous TS/PTD CNV studies, with CNV calls generated from 5,725 TS/PTD cases and 10,982 matched controls. The results confirmed that TS/PTD cases 1) have a higher burden of ultra-rare deletions overlapping loss-of-function intolerant genes (OR = 1.68, P = 9.3×10^-5) and 2) are more likely to carry established neurodevelopmental CNVs (OR = 1.42, P = 3.9×10^-2) compared to controls. Additionally, a novel, genome-wide significant CNV locus for TS/PTD was discovered, involving duplications at 17q12 (hg19 chr17:34.8 - 36.2 Mb). This locus is associated with a known duplication syndrome associated with variable neuropsychiatric traits, but has not been previously linked to tic disorders. Eight cases and one control carried the canonical ~1.4 Mb duplication at chr17:34.8 - 36.2 Mb, while one additional case had a smaller 110 kb duplication within this known CNV that included only one gene, ACACA (acetyl-CoA carboxylase, OR = 26.7, P = 5.69×10^-7). Overall, this study provides further evidence that rare, genic CNVs play a substantial role in the genetic architecture of TS/PTD and identifies a new genome-wide significant association with this neurodevelopmental disorder.

Background Obsessive-compulsive disorder (OCD) is associated with an increased risk of morbidity and mortality due to cardiometabolic disorders. Whether this association is driven by familial factors is unknown. This population-based family study explored the familial co-aggregation of OCD and cardiometabolic disorders.Methods We identified 6 049 717 individuals born in Sweden between 1950 and 2008, including 50 212 individuals with OCD, and followed them up to 2020. These individuals were linked to their mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles and cousins. We estimated the risk of cardiovascular diseases (CVD) and metabolic disorders (including obesity, type 2 diabetes and hyperlipidaemia), comparing the relatives of probands with and without OCD. Cox proportional hazards regression models, incorporating time-varying exposures, estimated HRs.Results OCD was associated with an increased risk of CVD (HR 1.47; 95% CI 1.43 to 1.51), obesity (HR 1.69; 95% CI 1.63 to 1.74), type 2 diabetes (HR 2.01; 95% CI 1.90 to 2.12) and hyperlipidaemia (HR 1.42; 95% CI 1.33 to 1.52). The relatives of probands with OCD exhibited small increased risks of CVD (HRs from 1.01 to 1.11) and obesity (HRs from 1.03 to 1.20). Slightly increased risks for type 2 diabetes were observed in mothers (HR 1.11; 95% CI 1.07 to 1.15) and full siblings (HR 1.12; 95% CI 1.05 to 1.20), while for hyperlipidaemia it was only observed in mothers (HR 1.06; 95% CI 1.02 to 1.10).Conclusions Our results do not support a major contribution of familial factors to the association between OCD and cardiometabolic disorders, suggesting a more prominent role of unique environmental factors.