Intentional self-harm and death by suicide in body dysmorphic disorder:A nationwide cohort study.

OBJECTIVES: Body dysmorphic disorder (BDD) is thought to be associated with considerable suicide risk. This nationwide cohort study quantified the risks of intentional self-harm - including non-suicidal self-injuries and suicide attempts - and death by suicide in BDD. METHODS: Individuals with a validated ICD-10 diagnosis of BDD in the Swedish National Patient Register, registered between January 1, 1997 and December 31, 2020, were matched with 10 unexposed individuals from the general population on birth year, sex, and county of residence. Conditional Poisson regression models estimated incidence rate ratios (IRR) and 95% confidence intervals (CIs) for intentional self-harm and stratified Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs for death by suicide. Models adjusted for sociodemographic variables and lifetime psychiatric comorbidities. RESULTS: Among 2,833 individuals with BDD and 28,330 unexposed matched individuals, 466 (16.45%) and 1,071 (3.78%) had at least one record of intentional self-harm during the study period, respectively (IRR=3.37; 95% CI, 3.02-3.76). In the BDD cohort, about two thirds (n=314; 67%) had their first recorded self-harm event before their first BDD diagnosis. A total of 17 (0.60%) individuals with BDD and 27 (0.10%) unexposed individuals died by suicide (HR=3.47; 95% CI, 1.76-6.85). All results remained robust to additional adjustment for lifetime psychiatric comorbidities. A higher proportion of individuals with BDD who died by suicide had at least one previous record of intentional self-harm, compared to unexposed individuals (52.94% vs. 22.22%; p=0.0363). CONCLUSIONS: BDD was associated with a three-fold increased risk of intentional self-harm and death by suicide.

Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome: 12-Month Follow-Up of a Randomized Clinical Trial.

Importance: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. Objective: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. Design, Setting, And Participants: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. Interventions: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. Main Outcomes And Measures: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). Results: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. Conclusions And Relevance: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. Trial Registration: ClinicalTrials.gov Identifier: NCT03916055.

WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production.

BACKGROUND AND AIMS: Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis. METHODS: We investigated the intestinal health of Wnt2b knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, as well as the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue. RESULTS: Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis due to an increased early injury response. While ISC markers were decreased, epithelial proliferation was similar to controls. Wnt2b KO mice showed an enhanced inflammatory signature after DSS treatment. Wnt2b KO colon and human WNT2B-deficient organoids both had increased levels of CXCR4 and IL6, and biopsy tissue from humans showed increased neutrophils. CONCLUSION: WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.

Practitioner Review: Assessment and treatment of body dysmorphic disorder in young people.

Body dysmorphic disorder (BDD) is a relatively common and highly impairing mental disorder that is strikingly underdiagnosed and undertreated in Child and Adolescent Mental Health Services (CAMHS). The only clinical guidelines for the management of BDD in youth were published nearly 20 years ago, when empirical knowledge was sparse. Fortunately, there has been a surge in research into BDD over the last 10 years, shedding important insights into the phenomenology, epidemiology, assessment and treatment of the disorder in young people. This review aimed to provide an overview of recent research developments of relevance to clinicians and healthcare policymakers. We summarise key findings regarding the epidemiology of BDD in youth, which indicate that the disorder usually develops during teenage years and affects approximately 2% of adolescents at any one point in time. We provide an overview of aetiological research, highlighting that BDD arises from an interplay between genetic and environmental influences. We then focus on screening and assessment strategies, arguing that these are crucial to promote detection and diagnosis of this under-recognised condition. Additionally, we summarise the recommended treatment approaches for BDD in youth, namely cognitive behaviour therapy with or without selective serotonin reuptake inhibitors. The review concludes by highlighting key knowledge gaps and priorities for future research including, but not limited to, better understanding aetiological factors, long-term consequences and treatment.

Family accommodation in obsessive-compulsive disorder: An updated systematic review and meta-analysis.

Family accommodation might play a crucial role in obsessive-compulsive disorder (OCD). Previous systematic reviews on family accommodation in OCD have focused on specific populations or variables or are outdated. We conducted a preregistered systematic review and meta-analysis on family accommodation in adults, children, and adolescents with OCD (CRD42021264461). We searched PubMed, Scopus, and Web of Science using the keywords "family accommodation" and "obsessive-compulsive disorder. One hundred-eight studies involving 8928 individuals with OCD were included. Our results indicate that levels of family accommodation in OCD are moderate, that there is a significant positive correlation between family accommodation and OCD severity (r = 0.42), that baseline family accommodation does not predict pre- to post-treatment change in OCD severity (g = -0.03), and that family accommodation decreases as a result of both individual and family-focused cognitive behavioral therapy for OCD (g = 2.00 and g = 1.17, respectively). Our findings highlight the relevance of family accommodation in OCD and may help guide assessment and treatment.

The journey of a generation: advances and promises in the study of primordial germ cell migration.

The germline provides the genetic and non-genetic information that passes from one generation to the next. Given this important role in species propagation, egg and sperm precursors, called primordial germ cells (PGCs), are one of the first cell types specified during embryogenesis. In fact, PGCs form well before the bipotential somatic gonad is specified. This common feature of germline development necessitates that PGCs migrate through many tissues to reach the somatic gonad. During their journey, PGCs must respond to select environmental cues while ignoring others in a dynamically developing embryo. The complex multi-tissue, combinatorial nature of PGC migration is an excellent model for understanding how cells navigate complex environments in vivo. Here, we discuss recent findings on the migratory path, the somatic cells that shepherd PGCs, the guidance cues somatic cells provide, and the PGC response to these cues to reach the gonad and establish the germline pool for future generations. We end by discussing the fate of wayward PGCs that fail to reach the gonad in diverse species. Collectively, this field is poised to yield important insights into emerging reproductive technologies.

Heritability of Clinically Diagnosed Obsessive-Compulsive Disorder Among Twins.

This cohort study estimates the heritability of clinically diagnosed obsessive-compulsive disorder in a sample of twins.

Body-Focused Repetitive Behavior Disorders in Children and Adolescents: Clinical Characteristics and Treatment Outcomes in a Naturalistic Setting.

Body-focused repetitive behavior disorders, including trichotillomania (hair-pulling disorder) and excoriation (skin picking) disorder, typically emerge in early adolescence, but little is known about the clinical characteristics and treatment outcomes of these disorders in young people, particularly in real-world clinical settings. Participants were 63 children and adolescents (51 girls; age range 9-17) with a diagnosis of trichotillomania (n = 33) and/or skin-picking disorder (n = 33) attending a specialist outpatient clinic in Stockholm, Sweden. Demographic and clinical characteristics were gathered at the initial assessment. Of the 63 assessed youths, 56 received manual-based behavior therapy mainly focusing on habit reversal training, which was combined with medication when deemed appropriate. The mean clinician-reported trichotillomania and skin-picking disorder symptom severity at baseline (n = 63) was in the moderate range. We observed high rates of psychiatric comorbidity (63.5%) and use of psychiatric medication (54.8%). For the 56 individuals undertaking treatment at the clinic, mixed-effects regression models showed a significant decrease in symptom severity from baseline to posttreatment, with gains maintained up to the 12-month follow-up. Substantial and durable improvements were also seen on self-reported symptoms, self-reported depression, and global functioning. Specialist care should be made more widely available to improve the prognosis and quality of life of young people with trichotillomania and skin-picking disorder.

General somatic health and lifestyle habits in individuals with obsessive- compulsive disorder: an international survey.

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.

Psychometric evaluation of the appearance anxiety inventory in adolescents with body dysmorphic disorder.

The Appearance Anxiety Inventory (AAI) is a self-report measure assessing the typical cognitions and behaviours of body dysmorphic disorder (BDD). Despite its use in research and clinical settings, its psychometric properties have not been evaluated in young people with BDD. We examined the factor structure, reliability, validity, and sensitivity to change of the AAI in 182 youths with BDD (82.9% girls; Mage = 15.56, SD = 1.37) consecutively referred to two specialist outpatient clinics in Stockholm, Sweden (n = 97) and London, England (n = 85). An exploratory factor analysis identified three factors, namely "threat monitoring", "camouflaging", and "avoidance", explaining 48.15% of the variance. The scale showed good internal consistency (McDonalds omega = 0.83) and adequate convergent validity with the Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder for Adolescents (BDD-YBOCS-A; rs = 0.42) and the Clinical Global Impression-Severity Scale (rs = 0.32). Sensitivity to change was adequate, with AAI total scores and individual factor scores significantly decreasing over time in the subgroup of participants receiving multimodal treatment for BDD (n = 79). Change of AAI scores over treatment showed a positive statistically significant moderate-to-good correlation (r = 0.55) with changes in BDD symptom severity, measured by the BDD-YBOCS-A. The study provides empirical support for the use of the AAI in young people with BDD in clinical settings.

All cause and cause specific mortality in obsessive-compulsive disorder: nationwide matched cohort and sibling cohort study.

OBJECTIVE: To estimate the risk of all cause and cause specific mortality in people with obsessive-compulsive disorder (OCD) compared with matched unaffected people from the general population and with their unaffected siblings. DESIGN: Population based matched cohort and sibling cohort study. SETTING: Register linkage in Sweden. PARTICIPANTS: Population based cohort including 61 378 people with OCD and 613 780 unaffected people matched (1:10) on sex, birth year, and county of residence; sibling cohort consisting of 34 085 people with OCD and 47 874 unaffected full siblings. Cohorts were followed up for a median time of 8.1 years during the period from 1 January 1973 to 31 December 2020. MAIN OUTCOME MEASURES: All cause and cause specific mortality. RESULTS: 4787 people with OCD and 30 619 unaffected people died during the study period (crude mortality rate 8.1 and 5.1 per 1000 person years, respectively). In stratified Cox proportional hazards models adjusted for birth year, sex, county, migrant status (born in Sweden versus abroad), and sociodemographic variables (latest recorded education, civil status, and family income), people with OCD had an increased risk of all cause mortality (hazard ratio 1.82, 95% confidence interval 1.76 to 1.89) and mortality due to natural causes (1.31, 1.27 to 1.37) and unnatural causes (3.30, 3.05 to 3.57). Among the natural causes of death, those due to endocrine, nutritional, and metabolic diseases, mental and behavioural disorders, and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems were higher in the OCD cohort. Conversely, the risk of death due to neoplasms was lower in the OCD cohort compared with the unaffected cohort. Among the unnatural causes, suicide showed the highest hazard ratio, followed by accidents. The results were robust to adjustment for psychiatric comorbidities and familial confounding. CONCLUSIONS: Non-communicable diseases and external causes of death, including suicides and accidents, were major contributors to the risk of mortality in people with OCD. Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD.

All-Cause and Cause-Specific Mortality Among Individuals With Hypochondriasis.

Importance: Hypochondriasis, also known as health anxiety disorder, is a prevalent, yet underdiagnosed psychiatric disorder characterized by persistent preoccupation about having serious and progressive physical disorders. The risk of mortality among individuals with hypochondriasis is unknown. Objective: To investigate all-cause and cause-specific mortality among a large cohort of individuals with hypochondriasis. Design, Setting, and Participants: This Swedish nationwide matched-cohort study included 4129 individuals with a validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of hypochondriasis assigned between January 1, 1997, and December 31, 2020, and 41 290 demographically matched individuals without hypochondriasis. Individuals with diagnoses of dysmorphophobia (body dysmorphic disorder) assigned during the same period were excluded from the cohort. Statistical analyses were conducted between May 5 and September 27, 2023. Exposure: Validated ICD-10 diagnoses of hypochondriasis in the National Patient Register. Main Outcome and Measures: All-cause and cause-specific mortality in the Cause of Death Register. Covariates included birth year, sex, county of residence, country of birth (Sweden vs abroad), latest recorded education, civil status, family income, and lifetime psychiatric comorbidities. Stratified Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs of all-cause and cause-specific mortality. Results: Of the 4129 individuals with hypochondriasis (2342 women [56.7%]; median age at first diagnosis, 34.5 years [IQR, 26.3-46.1 years]) and 41 290 demographically matched individuals without hypochondriasis (23 420 women [56.7%]; median age at matching, 34.5 years [IQR, 26.4-46.2 years]) in the study, 268 individuals with hypochondriasis and 1761 individuals without hypochondriasis died during the study period, corresponding to crude mortality rates of 8.5 and 5.5 per 1000 person-years, respectively. In models adjusted for sociodemographic variables, an increased rate of all-cause mortality was observed among individuals with hypochondriasis compared with individuals without hypochondriasis (HR, 1.69; 95% CI, 1.47-1.93). An increased rate was observed for both natural (HR, 1.60; 95% CI, 1.38-1.85) and unnatural (HR, 2.43; 95% CI, 1.61-3.68) causes of death. Most deaths from unnatural causes were attributed to suicide (HR, 4.14; 95% CI, 2.44-7.03). The results were generally robust to additional adjustment for lifetime psychiatric disorders. Conclusions and Relevance: This cohort study suggests that individuals with hypochondriasis have an increased risk of death from both natural and unnatural causes, particularly suicide, compared with individuals from the general population without hypochondriasis. Improved detection and access to evidence-based care should be prioritized.

Association of pre-existing maternal cardiovascular diseases with neurodevelopmental disorders in offspring: a cohort study in Sweden and British Columbia, Canada.

BACKGROUND: We aimed to investigate the associations of pre-existing maternal cardiovascular disease (CVD) with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) in offspring. METHODS: This population-based cohort study included singletons live-born without major malformations in Sweden (n = 2 699 675) and British Columbia (BC), Canada (n = 887 582) during 1990-2019, with follow-up from age 1 year until the outcome, death, emigration or December 2020, whichever came first. The primary exposure was defined as a composite CVD diagnosed prior to conception: cerebrovascular disease, arrhythmia, heart failure, valvular and congenital heart diseases. The incidences of ADHD, ASD and ID, comparing offspring of mothers with versus without CVD, were calculated as adjusted hazard ratios (aHRs). These results were compared with models using paternal CVD as negative control exposure. RESULTS: Compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD [95% confidence interval (CI): 1.10-1.20] and ASD (95% CI 1.07-1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (HR 1.31, 95% CI 1.02-1.61), cerebrovascular disease (HR 1.20, 95% CI 1.08-1.32), congenital heart disease (HR 1.18, 95% CI 1.08-1.27), arrhythmia (HR 1.13, 95% CI 1.08-1.19) and valvular heart disease (HR 1.12, 95% CI 1.00-1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (HR 1.25, 95% CI 1.04-1.46), congenital heart disease (HR 1.17, 95% CI 1.01-1.33) and arrythmia (HR 1.12, 95% CI 1.01-1.21). Paternal CVD did not show associations with ADHD, ASD or ID, except for cerebrovascular disease which showed associations with ADHD and ASD. CONCLUSIONS: In this large cohort study, pre-existing maternal CVD was associated with increased risk of ADHD and ASD in offspring.

Therapist-guided, Internet-delivered cognitive behaviour therapy for adolescents with body dysmorphic disorder: A feasibility trial with long-term follow-up.

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.

Influence of Initial Treatment Strategy on Outcomes for Children With Rectal Prolapse.

OBJECTIVE: Pediatric rectal prolapse is a common and often self-limited condition with multiple management options. Selecting the optimal approach requires personalization and remains a challenge for pediatricians and pediatric surgeons. METHODS: A single-center retrospective review of 67 children with rectal prolapse undergoing surgical evaluation between 2010 and 2021. Patients with anorectal malformations, Hirschsprung disease, inflammatory bowel disease, and cystic fibrosis were excluded. We used multivariable logistic regression to compare medical management, sclerotherapy, and surgical correction (rectopexy or transanal resection) as initial treatment strategies, with a primary endpoint of prolapse resolution. RESULTS: Younger patients (<5 years) were more likely to be initially treated with medical management alone (P < 0.001). Patients with a psychiatric diagnosis were more likely to be offered either sclerotherapy or surgery upfront (P = 0.009). The resolution rate with surgery as initial management was 79% (n = 11/14). The resolution rate with sclerotherapy as initial management was 54% (n = 13/24), with 33% (n = 8/24) resolving with sclerotherapy alone and 21% (n = 5/24) resolving after a subsequent surgical procedure (P = 0.011). Patients who underwent initial surgical management had an adjusted odds ratio of 8.0 (95% CI: 1.1-59.1; P = 0.042) for resolution of prolapse compared to patients who underwent sclerotherapy initially. Markers of severity (bleeding, need for manual reduction) were not associated with initial therapy offered (P = 0.064). CONCLUSIONS: Surgical intervention (sclerotherapy, rectopexy, transanal resection) resolved rectal prolapse in most children (63%). Surgery as an initial management approach had a significantly higher success rate than sclerotherapy, even after controlling for severity of disease, psychiatric diagnosis, need for manual reduction, and age.

Swedish multimodal cohort of patients with anxiety or depression treated with internet-delivered psychotherapy (MULTI-PSYCH).

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.

Study protocol for a randomized controlled trial of in-home decluttering augmentation of group cognitive-behavioral therapy for hoarding disorder: the Joining Forces Trial.

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.

A Medium-Chain Fatty Acid Analogue Prevents Intestinal Failure-Associated Liver Disease in Preterm Yorkshire Piglets.

BACKGROUND & AIMS: At least 20%-30% of patients with intestinal failure receiving long-term parenteral nutrition will develop intestinal failure-associated liver disease (IFALD), for which there are few therapeutic options. SEFA-6179 is a first-in-class structurally engineered medium-chain fatty acid analogue that acts through GPR84, PPARα, and PPARγ agonism. We hypothesized that SEFA-6179 would prevent biochemical and histologic liver injury in a preterm piglet model of IFALD. METHODS: Preterm Yorkshire piglets were delivered by cesarean section, and parenteral nutrition was provided for 14 days via implanted central venous catheters. Animals were treated with either medium-chain triglyceride vehicle control or SEFA-6179. RESULTS: Compared to medium-chain triglyceride vehicle at day of life 15, SEFA-6179 prevented biochemical cholestasis (direct bilirubin: 1.9 vs <0.2 mg/dL, P = .01; total bilirubin: 2.7 vs 0.4 mg/dL, P = .02; gamma glutamyl transferase: 172 vs 30 U/L, P = .01). SEFA-6179 also prevented steatosis (45.6 vs 13.9 mg triglycerides/g liver tissue, P = .009), reduced bile duct proliferation (1.6% vs 0.5% area cytokeratin 7 positive, P = .009), and reduced fibrosis assessed by a masked pathologist (median Ishak score: 3 vs 1, P = 0.007). RNA sequencing of liver tissue demonstrated that SEFA-6179 broadly impacted inflammatory, metabolic, and fibrotic pathways, consistent with its in vitro receptor activity (GPR84/PPARα/PPARγ agonist). CONCLUSIONS: In a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis and reduced bile duct proliferation and fibrosis. SEFA-6179 is a promising first-in-class therapy for the prevention and treatment of IFALD that will be investigated in an upcoming phase II clinical trial.

Pregnancy, Delivery, and Neonatal Outcomes Associated With Maternal Obsessive-Compulsive Disorder: Two Cohort Studies in Sweden and British Columbia, Canada.

Importance: Obsessive-compulsive disorder (OCD) is associated with adverse health-related outcomes. However, pregnancy and neonatal outcomes among women with OCD have been sparsely studied. Objective: To evaluate associations of maternal OCD with pregnancy, delivery, and neonatal outcomes. Design, Setting, and Participants: Two register-based cohort studies in Sweden and British Columbia (BC), Canada, included all singleton births at 22 weeks or more of gestation between January 1, 1999 (Sweden), or April 1, 2000 (BC), and December 31, 2019. Statistical analyses were conducted between August 1, 2022, and February 14, 2023. Exposure: Maternal OCD diagnosis recorded before childbirth and use of serotonin reuptake inhibitors (SRIs) during pregnancy. Main Outcomes and Measures: Pregnancy and delivery outcomes examined were gestational diabetes, preeclampsia, maternal infection, antepartum hemorrhage or placental abruption, premature rupture of membranes, induction of labor, mode of delivery, and postpartum hemorrhage. Neonatal outcomes included perinatal death, preterm birth, small for gestational age, low birth weight (<2500 g), low 5-minute Apgar score, neonatal hypoglycemia, neonatal jaundice, neonatal respiratory distress, neonatal infections, and congenital malformations. Multivariable Poisson log-linear regressions estimated crude and adjusted risk ratios (aRRs). In the Swedish cohort, sister and cousin analyses were performed to account for familial confounding. Results: In the Swedish cohort, 8312 pregnancies in women with OCD (mean [SD] age at delivery, 30.2 [5.1] years) were compared with 2 137 348 pregnancies in unexposed women (mean [SD] age at delivery, 30.2 [5.1] years). In the BC cohort, 2341 pregnancies in women with OCD (mean [SD] age at delivery, 31.0 [5.4] years) were compared with 821 759 pregnancies in unexposed women (mean [SD] age at delivery, 31.3 [5.5] years). In Sweden, maternal OCD was associated with increased risks of gestational diabetes (aRR, 1.40; 95% CI, 1.19-1.65) and elective cesarean delivery (aRR, 1.39; 95% CI, 1.30-1.49), as well as preeclampsia (aRR, 1.14; 95% CI, 1.01-1.29), induction of labor (aRR, 1.12; 95% CI, 1.06-1.18), emergency cesarean delivery (aRR, 1.16; 95% CI, 1.08-1.25), and postpartum hemorrhage (aRR, 1.13; 95% CI, 1.04-1.22). In BC, only emergency cesarean delivery (aRR, 1.15; 95% CI, 1.01-1.31) and antepartum hemorrhage or placental abruption (aRR, 1.48; 95% CI, 1.03-2.14) were associated with significantly higher risk. In both cohorts, offspring of women with OCD were at elevated risk of low Apgar score at 5 minutes (Sweden: aRR, 1.62; 95% CI, 1.42-1.85; BC: aRR, 2.30; 95% CI, 1.74-3.04), as well as preterm birth (Sweden: aRR, 1.33; 95% CI, 1.21-1.45; BC: aRR, 1.58; 95% CI, 1.32-1.87), low birth weight (Sweden: aRR, 1.28; 95% CI, 1.14-1.44; BC: aRR, 1.40; 95% CI, 1.07-1.82), and neonatal respiratory distress (Sweden: aRR, 1.63; 95% CI, 1.49-1.79; BC: aRR, 1.47; 95% CI, 1.20-1.80). Women with OCD taking SRIs during pregnancy had an overall increased risk of these outcomes, compared with those not taking SRIs. However, women with OCD not taking SRIs still had increased risks compared with women without OCD. Sister and cousin analyses showed that at least some of the associations were not influenced by familial confounding. Conclusion and Relevance: These cohort studies suggest that maternal OCD was associated with an increased risk of adverse pregnancy, delivery, and neonatal outcomes. Improved collaboration between psychiatry and obstetric services and improved maternal and neonatal care for women with OCD and their children is warranted.

In search of environmental risk factors for obsessive-compulsive disorder: study protocol for the OCDTWIN project.

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.