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.

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.

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.

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.

Early-Life and Family Risk Factors for Tic Disorder Persistence into Adulthood.

BACKGROUND: Many children with tic disorders outgrow their tics, but little is known about the proportion of individuals who will continue to require specialist services in adulthood and which variables are associated with tic persistence. OBJECTIVES: The aims were to estimate the proportion of individuals first diagnosed with tic disorders in childhood who continued to receive tic disorder diagnoses after age 18 years and to identify risk factors for persistence. METHODS: In this Swedish nationwide cohort study including 3761 individuals diagnosed with tic disorders in childhood, we calculated the proportion of individuals whose diagnoses persisted into adulthood. Minimally adjusted logistic regression models examined the associations between sociodemographic, clinical, and family variables and tic disorder persistence. A multivariable model was then fitted, including only variables that were statistically significant in the minimally adjusted models. RESULTS: Seven hundred and fifty-four (20%) children with tic disorders received a diagnosis of a chronic tic disorder in adulthood. Psychiatric comorbidity in childhood (particularly attention-deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorders, and anxiety disorders) and psychiatric disorders in first-degree relatives (particularly tic and anxiety disorders) were the strongest risk factors for persistence. We did not observe statistically significant associations with socioeconomic variables, perinatal complications, comorbid autoimmune diseases, or family history of autoimmune diseases. All statistically significant variables combined explained approximately 10% of the variance in tic disorder persistence (P < 0.0001). CONCLUSIONS: Childhood psychiatric comorbidities and family history of psychiatric disorders were the strongest risk factors associated with tic disorder persistence into adulthood. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Maternal suicide attempts and deaths in the first year after cesarean delivery.

BACKGROUND: Cesarean delivery (CD) has been associated with postpartum psychiatric disorders, but less is known about the risk of suicidal behaviors. We estimated the incidence and risk of suicide attempts and deaths during the first postpartum year in mothers who delivered via CD v. vaginally. METHOD: All deliveries in Sweden between 1973 and 2012 were identified. The mothers were followed since delivery for 12 months or until the date of one of the outcomes (i.e. suicide attempt or death by suicide), death by other causes or emigration. Associations were estimated using Cox proportional hazards regression models. RESULTS: Of 4 016 789 identified deliveries, 514 113 (12.8%) were CDs and 3 502 676 (87.2%) were vaginal deliveries. During the 12-month follow-up, 504 (0.098%) suicide attempts were observed in the CD group and 2240 (0.064%) in the vaginal delivery group (risk difference: 0.034%), while 11 (0.0037%) deaths by suicide were registered in the CD group and 109 (0.0029%) in the vaginal delivery group (risk difference: 0.008%). Compared to vaginal delivery, CD was associated with an increased risk of suicide attempts [hazard ratio (HR) 1.46; 95% CI 1.32-1.60], but not of deaths by suicide (HR 1.44; 95% CI 0.88-2.36). CONCLUSIONS: Maternal suicidal behaviors during the first postpartum year were uncommon in Sweden. Compared to vaginal delivery, CD was associated with a small increased risk of suicide attempts, but not death by suicide. Improved understanding of the association between CD and maternal suicidal behaviors may promote more appropriate measures to improve maternal mental well-being and further reduce suicidal risks.

Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison.

Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973-2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32-36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.12] and sibling analyses (HR 1.10, 95% CI 1.02-1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

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.

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.

Psychometric Evaluation of the Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder for Adolescents (BDD-YBOCS-A).

The Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder for Adolescents (BDD-YBOCS-A) is a clinician-rated measure of BDD symptom severity in youth. Despite widespread use in both research and clinical practice, its psychometric properties have not been formally evaluated. The current study examined the factor structure, reliability, validity, and sensitivity to change of the BDD-YBOCS-A in 251 youths with BDD attending two specialist clinics. A principal component analysis identified two factors, explaining 56% of the variance. The scale showed good internal consistency (Cronbach's alpha = 0.87) and adequate convergent and divergent validity. In a subgroup of participants receiving BDD treatment (n = 175), BDD-YBOCS-A scores significantly decreased over time, demonstrating sensitivity to change. BDD-YBOCS-A change scores over treatment were highly correlated with severity changes measured by the Clinical Global Impression - Severity scale (r = .84). The study provides empirical support for the use of the BDD-YBOCS-A in children and adolescents with BDD.

Insomnia in Tourette Syndrome and Chronic Tic Disorder.

BACKGROUND: Insomnia is common in Tourette syndrome (TS) and chronic tic disorder (CTD), but precise prevalence estimates are lacking. OBJECTIVE: In this Swedish register-based cohort study, we estimated the prevalence of insomnia in TS/CTD and quantified the magnitude of this association, accounting for familial confounders and relevant somatic and psychiatric comorbidities. METHODS: Of 10,444,702 individuals living in Sweden during the period from 1997 to 2013, 5877 had a diagnosis of TS/CTD and were compared to unexposed individuals from the general population on the presence of insomnia using logistic regression models. RESULTS: Individuals with TS/CTD had a period prevalence of insomnia of 32.16%, compared to 13.70% of the unexposed population. This translated into a 6.7-fold increased likelihood of insomnia in TS/CTD (odds ratio adjusted [aOR] for sex, birth year, birth country, and somatic disorders = 6.74; 95% confidence interval [CI], 6.37-7.15). A full sibling comparison, designed to adjust for shared familial factors, attenuated the estimates (aOR = 5.41; 95% CI, 4.65-6.30). When individuals with attention-deficit/hyperactivity disorder (ADHD) and pervasive developmental disorders were excluded, the association was also attenuated, whereas exclusion of other psychiatric comorbidities had minimal impact. Having persistent TS/CTD, comorbid ADHD, and taking ADHD medication greatly increased the likelihood of insomnia. CONCLUSIONS: Insomnia is significantly associated with TS/CTD, independently from somatic disorders, familial factors or psychiatric comorbidities, although familial factors, neurodevelopmental comorbidities, and ADHD/ADHD medication may explain part of the association. Insomnia should be routinely assessed and managed in TS/CTD, particularly in chronic patients and in those with comorbid ADHD. Other sleep disorders require further study. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The association between body dysmorphic symptoms and suicidality among adolescents and young adults: a genetically informative study.

BACKGROUND: Previous research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown. METHODS: Two independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages. RESULTS: Suicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively). CONCLUSIONS: BDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk.

Genetic and environmental sources of familial coaggregation of obsessive-compulsive disorder and suicidal behavior: a population-based birth cohort and family study.

Obsessive-compulsive disorder (OCD) is associated with high risk of suicide. It is yet unknown whether OCD and suicidal behaviors coaggregate in families and, if so, what are the mechanisms underlying this coaggregation. In a population-based birth cohort and family study, we linked individuals born in Sweden in 1967-2003 (n = 3,594,181) to their parents, siblings, and cousins, and collected register-based diagnoses of OCD, suicide attempts, and deaths by suicide and followed them until December 31, 2013. We also applied quantitative genetic modeling to estimate the contribution of genetic and environmental factors to the familial coaggregation of OCD and suicidal behavior. An elevated risk of suicide attempts was observed across all relatives of individuals with OCD, increasing proportionally to the degree of genetic relatedness, with odds ratios (OR) ranging from 1.56 (95% confidence interval (CI) 1.49-1.63) in parents to 1.11 (95% CI 1.07-1.16) in cousins. The risk of death by suicide also increased alongside narrowing genetic distance, but was only significant in parents (OR 1.55; 95% CI 1.40-1.72) and full siblings (OR 1.80; 95% CI 1.43-2.26) of individuals with OCD. Familial coaggregation of OCD and suicide attempts was explained by additive genetic factors (60.7%) and non-shared environment (40.4%), with negligible contribution of shared environment. Similarly, familial coaggregation with death by suicide was attributed to additive genetics (65.8%) and nonshared environment (34.2%). Collectively, these observations indicate that OCD and suicidal behaviors coaggregate in families largely due to genetic factors. The contribution of unique environment is also considerable, providing opportunities to target high-risk groups for prevention and treatment.

A population-based family clustering study of tic-related obsessive-compulsive disorder.

In the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), obsessive-compulsive disorder (OCD) included a new "tic-related" specifier. However, strong evidence supporting tic-related OCD as a distinct subtype of OCD is lacking. This study investigated whether, at the population level, tic-related OCD has a stronger familial load than non-tic-related OCD. From a cohort of individuals born in Sweden between 1967 and 2007 (n = 4,085,367; 1257 with tic-related OCD and 20,975 with non-tic-related OCD), we identified all twins, full siblings, maternal and paternal half siblings, and cousins. Sex- and birth year-adjusted hazard ratios (aHR) were calculated to estimate the risk of OCD in relatives of individuals with OCD with and without comorbid tics, compared with relatives of unaffected individuals. We found that OCD is a familial disorder, regardless of comorbid tic disorder status. However, the risk of OCD in relatives of individuals with tic-related OCD was considerably greater than the risk of OCD in relatives of individuals with non-tic-related OCD (e.g., risk for full siblings: aHR = 10.63 [95% CI, 7.92-14.27] and aHR = 4.52 [95% CI, 4.06-5.02], respectively; p value for the difference < 0.0001). These differences remained when the groups were matched by age at first OCD diagnosis and after various sensitivity analyses. The observed familial patterns of OCD in relation to tics were not seen in relation to other neuropsychiatric comorbidities. Tic-related OCD is a particularly familial subtype of OCD. The results have important implications for ongoing gene-searching efforts.

Operational Definitions of Treatment Response and Remission in Obsessive-Compulsive Disorder Capture Meaningful Improvements in Everyday Life.

INTRODUCTION: The operational definitions of treatment response, partial response, and remission in obsessive-compulsive disorder (OCD) are widely used in clinical trials and regular practice. However, the clinimetric sensitivity of these definitions, that is, whether they identify patients that experience meaningful changes in their everyday life, remains unexplored. OBJECTIVE: The objective was to examine the clinimetric sensitivity of the operational definitions of treatment response, partial response, and remission in children and adults with OCD. METHODS: Pre- and post-treatment data from five clinical trials and three cohort studies of children and adults with OCD (n = 1,528; 55.3% children, 61.1% female) were pooled. We compared (1) responders, partial responders, and non-responders and (2) remitters and non-remitters on self-reported OCD symptoms, clinician-rated general functioning, and self-reported quality of life. Remission was also evaluated against post-treatment diagnostic interviews. RESULTS: Responders and remitters experienced large improvements across validators. Responders had greater improvements than partial responders and non-responders on self-reported OCD symptoms (Cohen's d 0.65-1.13), clinician-rated functioning (Cohen's d 0.53-1.03), and self-reported quality of life (Cohen's d 0.63-0.73). Few meaningful differences emerged between partial responders and non-responders. Remitters had better outcomes across most validators than non-remitters. Remission criteria corresponded well with absence of post-treatment diagnosis (sensitivity/specificity: 93%/83%). Using both the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression Scale yielded more conservative results and more robust changes across validators, compared to only using the Y-BOCS. CONCLUSIONS: The current definitions of treatment response and remission capture meaningful improvements in the everyday life of individuals with OCD, whereas the concept of partial response has dubious clinimetric sensitivity.

Hit-and-run: a Swedish nationwide cohort study of serious transport accidents and convictions due to traffic offenses in obsessive-compulsive disorder.

PURPOSE: Individuals with obsessive-compulsive disorder (OCD) often report driving-related obsessions, such as fears of causing accidents, but the risk of transport accidents in OCD is unknown. We investigated whether individuals with OCD have an increased risk of serious transport accidents and convictions due to traffic offenses and explored the role of psychiatric comorbidities. METHODS: We included all individuals ≥ 18 years living in Sweden between 1997 and 2013 (N = 5,760,734). A total of 23,126 individuals had a diagnosis of OCD in the National Patient Register. We also identified 16,607 families with full siblings discordant for OCD. Cox proportional hazards regression models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of three outcomes in individuals with OCD, compared to unexposed individuals and their unexposed full siblings: injuries or deaths due to transport accidents, injuries or deaths due to motor vehicle accidents, and convictions related to traffic offenses. Psychiatric comorbidities were systematically adjusted for. RESULTS: Women, but not men, with OCD had a marginally increased risk of serious transport accidents (adjusted HR = 1.20 [95% CI 1.13-1.28]) and motor vehicle accidents (adjusted HR = 1.20 [95% CI 1.09-1.31]), compared to unaffected individuals. Neither women nor men with OCD had a significantly increased risk of convictions. The sibling comparisons showed no significant associations. When psychiatric comorbidities were adjusted for, several observed associations became non-significant or inversed (HRs and 95% CIs below one). CONCLUSION: The risks of serious transport accidents and driving-related criminal convictions in OCD are negligible and heavily influenced by psychiatric comorbidity.

Clinical characteristics of 172 children and adolescents with body dysmorphic disorder.

Body dysmorphic disorder (BDD) often starts in childhood, with most cases developing symptoms before age 18. Yet, BDD research has primarily focused on adults. We report the clinical characteristics of the world's largest cohort of carefully diagnosed youths with BDD and focus on previously unexplored sex and age differences. We systematically collected clinical data from 172 young people with BDD consecutively referred to 2 specialist pediatric obsessive-compulsive and related disorders outpatient clinics in Stockholm, Sweden and in London, England. A series of clinician-, self-, and parent-reported measures were administered. The cohort consisted of 136 girls, 32 boys, and 4 transgender individuals (age range 10-19 years). The mean severity of BDD symptoms was in the moderate to severe range, with more than one third presenting with severe symptoms and more than half showing poor or absent insight/delusional beliefs. We observed high rates of current psychiatric comorbidity (71.5%), past or current self-harm (52.1%), suicide attempts (11.0%), current desire for cosmetic procedures (53.7%), and complete school dropout (32.4%). Compared to boys, girls had significantly more severe self-reported BDD symptoms, depression, suicidal thoughts, and self-harm. Compared to the younger participants (14 or younger), older participants had significantly more severe compulsions and were more likely to report a desire for conducting cosmetic procedures. Adolescent BDD can be a severe and disabling disorder associated with significant risks and substantial functional impairment. The clinical presentation of the disorder is largely similar across sexes and age groups, indicating the importance of early detection and treatment. More research is needed specifically focusing on boys and pre-pubertal individuals with BDD.

Serious Transport Accidents in Tourette Syndrome or Chronic Tic Disorder.

BACKGROUND: It is unknown whether individuals with tic disorders are at increased risk for serious transport accidents. OBJECTIVES: The aim of this study was to investigate the risk for injuries or death caused by transport and motor vehicle accidents in individuals with Tourette syndrome or chronic tic disorder. METHODS: This population-based, sibling-controlled cohort study included all individuals aged ≥18 years living in Sweden between 1997 and 2013 (N = 6,127,290). A total of 3449 individuals had a registered diagnosis of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. We also identified 2191 families with full siblings discordant for tic disorders. Cox proportional hazards regression modeling was used to estimate the risk for injuries or deaths as a result of transport accidents in individuals with a lifetime diagnosis of Tourette syndrome or chronic tic disorder compared with unexposed individuals and siblings. RESULTS: Individuals with tic disorders had a higher risk for transport injuries or death compared with the general population (adjusted hazard ratio, 1.50 [95% confidence interval: 1.33-1.69]) and their unaffected siblings (adjusted hazard ratio, 1.41 [95% confidence interval: 1.18-1.68]). The risks were similar across sexes. The exclusion of most psychiatric comorbidities did not alter the magnitude of the estimates. However, the risks were no longer significant after exclusion of individuals with comorbid attention deficit hyperactivity disorder. CONCLUSIONS: The marginally increased risk for serious transport accidents in tic disorders is mainly driven by attention deficit hyperactivity disorder comorbidity. Improved detection and management of attention deficit hyperactivity disorder symptoms in this patient group are warranted. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.