The genetic architecture of youth anxiety: a study protocol.

BACKGROUND: Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. METHODS: The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10-19 (n = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span. DISCUSSION: Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world.

Racial/Ethnic Disparities in Psychiatric Traits and Diagnoses within a Community-based Sample of Children and Youth: Disparités raciales/ethniques dans les traits et diagnostics psychiatriques au sein d'un échantillon communautaire d'enfants et de jeunes.

OBJECTIVE: Racial/ethnic disparities in the prevalence of psychiatric disorders have been reported, but have not accounted for the prevalence of the traits that underlie these disorders. Examining rates of diagnoses in relation to traits may yield a clearer understanding of the degree to which racial/ethnic minority youth in Canada differ in their access to care. We sought to examine differences in self/parent-reported rates of diagnoses for obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders after adjusting for differences in trait levels between youth from three racial/ethnic groups: White, South Asian and East Asian. METHOD: We collected parent or self-reported ratings of OCD, ADHD and anxiety traits and diagnoses for 6- to 17-year-olds from a Canadian general population sample (Spit for Science). We examined racial/ethnic differences in trait levels and the odds of reporting a diagnosis using mixed-effects linear models and logistic regression models. RESULTS: East Asian (N = 1301) and South Asian (N = 730) youth reported significantly higher levels of OCD and anxiety traits than White youth (N = 6896). East Asian and South Asian youth had significantly lower odds of reporting a diagnosis for OCD (odds ratio [OR]East Asian = 0.08 [0.02, 0.41]; ORSouth Asian = 0.05 [0.00, 0.81]), ADHD (OREast Asian = 0.27 [0.16, 0.45]; ORSouth Asian = 0.09 [0.03, 0.30]) and anxiety (OREast Asian = 0.21 [0.11, 0.39]; ORSouth Asian = 0.12 [0.05, 0.32]) than White youth after accounting for psychiatric trait levels. CONCLUSIONS: These results suggest a discrepancy between trait levels of OCD, ADHD and anxiety and rates of diagnoses for East Asian and South Asian youth. This discrepancy may be due to increased barriers for ethnically diverse youth to access mental health care. Efforts to understand and mitigate these barriers in Canada are needed.

We know that there is there are differences in the prevalence of childhood mental illnesses by race/ethnic group, which may be related to disproportionate access to mental health care. What is unknown is whether there this difference in prevalence is related to differences in the presence of symptoms for mental illness or whether children and youth from marginalized racial/ethnic groups have symptoms but are not getting diagnosed. This information is needed to understand the degree to which children and youth from marginalized race/ethnicity groups are accessing mental health care in Canada. We tested the differences in reported symptoms and diagnosis of three common and impairing childhood-onset disorders (obsessive-compulsive disorder­OCD), attention-deficit/hyperactivity disorder­ADHD and anxiety disorders) in children and youth (6­17 years of age) living in Canada that were from three racial/ethnic groups: White, South Asian and East Asian. East Asian and South Asian youth reported significantly higher levels of OCD and anxiety traits than White youth. However, East Asian and South Asian youth were significantly less likely than White youth to have a reported diagnosis of OCD, ADHD or anxiety even after accounting for symptom levels for each disorder. Our findings suggest that East and South Asian children are less likely than White children to get a diagnosis for common mental illness even if they have symptoms of that mental illness. This gap in receiving a diagnosis might be because of more barriers to mental health care for children and youth from marginalized racial/ethnic groups but we need more research to pinpoint the cause.

Exploring latent clusters in pediatric OCD based on symptoms, severity, age, gender, and comorbidity.

Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children's Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by symptom expression and comorbidity type. Fit indices for 3-7 cluster models were only marginally different and characteristics of the clusters remained largely stable between solutions with small clusters of distinct presentations added in more complex models. Rather than identifying a single classification system, the findings support the utility of integrating dimensional, developmental, and transdiagnostic information in the conceptualization of OCD-affected children and adolescents. Identified clusters point to the centrality of contamination concerns to OCD, relationships between broader symptom expression and higher levels of comorbidity, and the potential for complex/neurodevelopmental presentations.

Neurocognitive effects of transcranial direct current stimulation in obsessive-compulsive disorder: a systematic review.

Transcranial direct current stimulation (tDCS) has been used with increasing frequency as a therapeutic tool to alleviate clinical symptoms of obsessive compulsive-disorder (OCD). However, little is known about the effects of tDCS on neurocognitive functioning among OCD patients. The aim of this review was to provide a comprehensive overview of the literature examining the effects of tDCS on specific neurocognitive functions in OCD. A literature search following PRISMA guidelines was conducted on the following databases: PubMed, PsycINFO, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. The search yielded 4 results: one randomized, sham-controlled study (20 patients), one randomized, controlled, partial crossover trial (12 patients), one open-label study (5 patients), and one randomized, double-blind, sham-controlled, parallel-group trial (37 patients). A total of 51 patients received active tDCS with some diversity in electrode montages targeting the dorsolateral prefrontal cortex, the pre-supplementary motor area, or the orbitofrontal cortex. tDCS was associated with improved decision-making in study 1, enhanced attentional monitoring and response inhibition in study 2, improved executive and inhibitory control in study 3, and reduced attentional bias and improved response inhibition and working memory in study 4. Limitations of this review include its small sample, the absence of a sham group in half of the studies, and the heterogeneity in tDCS parameters. These preliminary results highlight the need for future testing in randomized, sham-controlled trials to examine whether and how tDCS induces relevant cognitive benefits in OCD.

Obsessive-compulsive disorder in children and youth: neurocognitive function in clinic and community samples.

BACKGROUND: Neurocognitive impairments are common in OCD, although not well studied in children and youth with the disorder. METHOD: Using the stop-signal task (SST), we measured response inhibition (stop-signal reaction time-SSRT), sustained attention (reaction time variability-RTV), reaction time (RT), and performance monitoring (post-error slowing-PES) in OCD cases and controls from two samples of children and youth. A Clinic OCD group (n = 171, aged 7-17 years) was recruited from a specialty clinic after rigorous assessment. A typically developing (Clinic TD, n = 157) group was enlisted through advertisement. A community OCD sample (Community OCD, n = 147) and controls (Community TD n = 13,832, aged 6-17 years) were recruited at a science museum. We also identified a community group with high OCD traits without an OCD diagnosis (Community High Trait; n = 125). RESULTS: Clinic OCD participants had longer SSRT and greater RTV than Clinic TD. These effects were greater in younger OCD participants and, for SSRT, in those on medication for OCD. The Community OCD group did not differ from Controls but was similar to the Clinic OCD group in ADHD and ASD comorbidity and medication usage. The Community High Trait group had longer SSRT and atypical PES suggesting that symptom severity predicts neurocognitive function. No group differences were found in RT. CONCLUSIONS: In the largest study of neurocognitive performance in children with OCD to date, we found impaired response inhibition and sustained attention in OCD participants in comparison to typically developing peers. Performance was worse in younger OCD participants. In the community sample, participants with high OCD trait scores but no OCD diagnosis had impaired response inhibition and error processing, suggesting that OCD might be under-recognized.

Exposure to stressful and traumatic life events in hoarding: Comparison to clinical controls.

BACKGROUND: Individuals with hoarding report stressful and traumatic life events at an elevated rate compared with those with obsessive-compulsive disorder and healthy controls, but have not been compared with other clinical groups. This study compared rates of traumatic life events between those with clinically significant hoarding, anxiety disorders, or posttraumatic stress disorder (PTSD), hypothesizing that rates would be higher in the hoarding and PTSD groups than the anxiety group. METHODS: Rates of traumatic and stressful events were compared across groups. RESULTS: All comparisons across groups on types of events were significant (partial-eta squared 0.051-0.162). The hoarding group endorsed significantly more crime-related events but similar rates of other events as compared to the PTSD and anxiety disorder groups. CONCLUSION: These findings suggest that many stressful and traumatic life events are not uniquely elevated in hoarding when compared with other clinical populations.

Hoarding: A meta-analysis of age of onset.

Hoarding disorder is present in 2-6% of the population and can have an immense impact on the lives of patients and their families. Before its inclusion the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, pathological hoarding was often characterized as a symptom of obsessive-compulsive disorder, and several different diagnostic assessment methods were used to identify and characterize it. Although the age of onset of pathological hoarding is an important epidemiological measure, as clarifying the age of onset of hoarding symptoms may allow for early identification and implementation of evidence-based treatments before symptoms become clinically significant, the typical age of onset of hoarding is still uncertain. To that end, this study is a systematic review and meta-analysis of research published in English between the years 1900 and 2016 containing information on age of onset of hoarding symptoms. Twenty-five studies met inclusion criteria. The mean age of onset of hoarding symptoms across studies was 16.7 years old, with evidence of a bimodal distribution of onset. The authors conclude by discussing practice implications for early identification and treatment.

Psychometric Evaluation of a Revised Scoring Approach for the Children's Saving Inventory in a Canadian Sample of Youth With Obsessive-Compulsive Disorder.

The Children's Saving Inventory (CSI) was introduced in 2011 and is the first parent-rated questionnaire specifically designed to measure the severity of hoarding symptoms in youth. To date, however, no replication studies of the CSI have been published. Additionally, the total CSI score includes several items measuring acquisition, a behavioural dimension that has since been excluded from DSM-5's hoarding disorder criteria. Given these limitations, the primary goal of the present study was to test a modified, DSM-5-consistent, total score of the CSI. Because a confirmatory factor analysis did not support the 2011 four-factor model of the CSI, we reviewed the original CSI and excluded all acquisition items. An exploratory factor analysis yielded a strong three-factor solution (difficulty discarding, Clutter, and distress/impairment) with good reliability and validity for a 15-item version of the CSI. Overall, our results support the use of the 15-item CSI in youth with OCD.

Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes.

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.

Standards of care for obsessive-compulsive disorder centres.

In recent years, many assessment and care units for obsessive-compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a standards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries.

A preliminary study on the effects of acute ethanol ingestion on default mode network and temporal fractal properties of the brain.

OBJECT: To study the effect of acute alcohol intoxication on the functional connectivity of the default mode network (DMN) and temporal fractal properties of the healthy adult brain. MATERIALS AND METHODS: Eleven healthy male volunteers were asked to drink 0.59 g/kg of ethanol. Resting state blood oxygen level dependent (rsBOLD) MRI scans were obtained before consumption, 60 min post-consumption and 90 min post-consumption. Before each rsBOLD scan, pointed-resolved spectroscopy (PRESS) (1)H-MRS (magnetic resonance spectroscopy) scans were acquired to measure ethanol levels in the right basal ganglia. RESULTS: Significant changes in DMN connectivity were found following alcohol consumption (p < 0.01). Both increased and decreased regional connectivity were found after 60 min, whereas mostly decreased connectivity was found after 90 min. The fractal behaviour of the rsBOLD signal, which is believed to help reveal complexity of small-scale neuronal circuitry, became more ordered after both 60 and 90 min of alcohol consumption (p < 0.01). CONCLUSION: The DMN has been linked to personal identity and social behavior. As such, our preliminary findings may provide insight into the neuro-functional underpinnings of the cognitive and behavioral changes observed during acute alcohol intoxication. The reduced fractal dimension implies a change in function of small-scale neural networks towards less complex signaling.

The Effects of a Single Transcranial Direct Current Stimulation Session on Impulsivity and Risk Among a Sample of Adult Recreational Cannabis Users.

Individuals with substance use disorders exhibit risk-taking behaviors, potentially leading to negative consequences and difficulty maintaining recovery. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have yielded mixed effects on risk-taking among healthy controls. Given the importance of risk-taking behaviors among substance-using samples, this study aimed to examine the effects of tDCS on risk-taking among a sample of adults using cannabis. Using a double-blind design, 27 cannabis users [M(SD) age = 32.48 (1.99), 41% female] were randomized, receiving one session of active or sham tDCS over the bilateral dorsolateral prefrontal cortex (dlPFC). Stimulation parameters closely followed prior studies with anodal right dlPFC and cathodal left dlPFC stimulation. Risk-taking-assessed via a modified Cambridge Gambling Task-was measured before and during tDCS. Delay and probability discounting tasks were assessed before and after stimulation. No significant effects of stimulation on risk-taking behavior were found. However, participants chose the less risky option ∼86% of the trials before stimulation which potentially contributed to ceiling effects. These results contradict one prior study showing increased risk-taking among cannabis users following tDCS. There was a significant increase in delay discounting of a $1000 delayed reward during stimulation for the sham group only, but no significant effects for probability discounting. The current study adds to conflicting and inconclusive literature on tDCS and cognition among substance-using samples. In conclusion, results suggest the ineffectiveness of single session dlPFC tDCS using an established stimulation protocol on risk-taking, although ceiling effects at baseline may have also prevented behavior change following tDCS.

Characterizing problematic internet use in a sample of heavy drinking emerging adults.

OBJECTIVE: Problematic internet use (PIU) is characterized by excessive or poorly controlled internet use resulting in impairment or distress. PIU is most prevalent during emerging adulthood, a period marked by an increase in psychiatric disorders, including substance use disorders (SUDs). In a sample of high-risk emerging adults, the aim of this study was to examine the relationship between PIU and quality of life (QoL), psychiatric disorders, and impulsivity. METHODS: Participants were a community sample of heavy drinking emerging adults in Hamilton, Ontario (N = 709). Measures included: PIU, QoL, eight psychiatric indicators, and three domains of impulsivity. All variables that were significantly associated with PIU were subsequently examined concurrently in structural equation models. RESULTS: PIU was negatively associated with physical QoL (ß = -0.27, p < .01) and social QoL (ß = -0.20, p < .01), but positively associated with environmental QoL (ß = 0.17, p < .01). For psychiatric conditions, PIU was positively associated with internalizing disorders (ß = 0.42, p < .01) but not SUD (ß = -0.01, p = .90). For impulsivity, PIU was positively associated with Lack of Perseverance (ß = 0.16, p < .01) and Negative Urgency (ß = 0.23, p < .01) but no other indicators. CONCLUSIONS: This study provides further evidence that PIU is associated with lower quality of life, selectively co-occurs with internalizing psychopathology, and is associated with certain impulsive traits. Lack of associations with SUD challenges conceptualizations of PIU as an alternative manifestation of externalizing psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does cannabis use impact cognitive behavioural therapy outcomes for anxiety and related disorders? A preliminary examination.

OBJECTIVES: The current study examined whether cannabis use frequency and cannabis-related problem severity (as per the Cannabis Use Disorder Identification Test-Revised) predicted outcomes of cognitive behavioural therapy (CBT) for anxiety and related disorders. It was predicted that greater frequency of cannabis use and greater cannabis-related problem severity would be associated with dampened treatment outcomes compared to less severe cannabis use presentations. METHODS: Participants were 253 adults seeking treatment for anxiety and related disorders. Cannabis use was categorized as non-use (n = 135), infrequent use (using monthly to 4 times per month; n = 45), and frequent use (using 2 or more times per week; n = 73). Individuals who reported using cannabis completed cannabis use and cannabis-related problem measures before starting a CBT group. Participants also completed a weekly symptom-specific measure of anxiety symptoms throughout CBT. RESULTS: As hypothesized, frequent cannabis use was associated with poorer outcomes in CBT for anxiety and related disorders compared to non-use. Despite this, individuals who used cannabis frequently still experienced a statistically significant decrease in their anxiety symptoms from pre-to post-CBT, with a large effect size (d = -0.87). Cannabis-related problems was not a significant predictor of CBT outcomes. CONCLUSIONS: Cannabis use frequency was associated with poorer CBT outcomes for anxiety and related disorders, however these individuals still made notable treatment gains. The mechanism driving this relationship remains unclear. Future studies should attempt to replicate the current findings and examine possible mechanisms.

Investigating executive functions in youth with OCD and hoarding symptoms.

Executive functions (EF) deficits are hypothesized to be a core contributor to hoarding symptoms. EF have been studied in adult hoarding populations, but studies in youth are lacking. The current study compared multiple EF subdomains between youth with obsessive-compulsive disorder (OCD) and youth with OCD and hoarding symptoms. Forty youth (8-18 years old) with a primary diagnosis of OCD were recruited. Participants were divided by hoarding severity on the Child Saving Inventory (CSI) into either the "hoarding group" (upper 33.3%) or the "low-hoarding group" (lower 66.7%). Groups were compared on EF tasks of cognitive flexibility, decision-making, and inhibitory control. Youth in the hoarding group exhibited significantly higher cognitive flexibility and lowered perseveration than the low-hoarding group. Hoarding and low-hoarding groups did not differ in any other EF subdomain. Hoarding symptoms in youth with OCD were not associated with deficits in EF subdomains; instead, youth who hoard exhibited higher cognitive flexibility compared to youth with low hoarding symptoms.

LIVES for families psychological first aid training programme to address COVID-19 psychological distress: a mixed methods acceptability and feasibility protocol.

INTRODUCTION: Best practice approaches for addressing COVID-19-related psychological distress among young people (<25 years) and their families remain unclear. Psychological first aid (PFA) is promoted by public health authorities to provide psychological support in the context of extreme events; however, there is limited evidence for its effectiveness. As a prerequisite to conducting a randomised controlled trial to examine programme effectiveness, this project is evaluating the acceptability and feasibility of implementing and evaluating a PFA training programme ('LIVES for Families') for mental health (MH) practitioners to improve their ability to recognise and respond to COVID-19-related psychological distress among their clients. METHODS AND ANALYSIS: We are using a triangulation mixed methods research design; complementary strands of quantitative and qualitative data are being collected in parallel and will be merged at the interpretation phase of the project. The quantitative strand uses a repeated measures design; a consecutive sample of MH practitioners (n=80) providing MH support to young people or their families are being recruited to participate in the LIVES for Families PFA training programme and complete quantitative measures at baseline (pretraining), 2-week and 6-month follow-up time points. The qualitative strand uses fundamental description and semistructured interviews with a subset of practitioners (n=30), as well as managers of MH agencies (n=20). A mixed methods joint display and associated narrative will generate a comprehensive understanding regarding acceptability and feasibility. ETHICS AND DISSEMINATION: The Hamilton Integrated Research Ethics Board approved the study (project number: 11295). Results will be shared broadly with the policy and practice community through publications, presentations and public webinars. As a brief, evidence-informed intervention, the LIVES for Families PFA training programme is suitable in its mode of delivery across care settings. The outcomes of this study could have international implications for mitigating the MH impacts of viral pandemics.

Clinical validation of the parent-report Toronto Obsessive-Compulsive Scale (TOCS): A pediatric open-source rating scale.

Background: There is a need to develop a multipurpose obsessive-compulsive disorder (OCD) measure that is useful for cross disorder research and as a reliable clinical rating scale. The current study examined the psychometric properties and established clinical cutoffs for the parent-report version of the Toronto Obsessive-Compulsive Scale (TOCS), a 21-item rating scale of obsessive-compulsive traits. Method: Participants ranged in age from 6 to 21 years old and had a primary diagnosis of OCD (n = 350, 50% female), attention-deficit/hyperactivity disorder (ADHD) (n = 820, 25% female), autism spectrum disorder (ASD) (n = 794, 22% female), or were typically developing controls (n = 391, 51% female). Confirmatory factor analyses, internal consistency reliability, and convergent and divergent validity of the TOCS were examined in the OCD group. Using various scoring approaches, receiver operating characteristic (ROC) analyses were used to establish a clinical cut-off by splitting the OCD group into a discovery sample (166 OCD cases, 164 controls) and a validation sample (184 OCD cases, 227 controls). Classification accuracy and TOCS scores were compared across OCD, ADHD, and ASD groups. Results: The psychometric properties of the TOCS were confirmed. ROC analyses across TOCS scoring approaches in the discovery sample indicated excellent diagnostic discrimination (AUC ≥0.95, sensitivity 77%-92%, specificity 92%-98%). Established cutoffs, when applied in the independent validation sample of OCD cases and controls, showed an overall classification accuracy of 85%-90%. The TOCS total score and symptom count showed good discrimination of OCD from ADHD (AUC ≥0.86) and ASD (AUC ≥0.81). The OCD group scored significantly higher on all TOCS dimensions (except Hoarding) than the ADHD and ASD groups. Conclusion: The TOCS is a reliable and valid rating scale with strong sensitivity and specificity in discriminating OCD cases from controls, as well as from ASD and ADHD. It is a quantitative OCD measure with important clinical and research applications, with particular relevance for cross disorder phenotyping and population-based studies.

Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder.

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10-8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p's < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (rg = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Interindividual, repositioning, and time-of-day effects on single voxel proton MR spectroscopy of the anterior cingulate cortex.

PURPOSE: To measure interindividual, repositioning, and time-of-day effects of single voxel PRESS (Point RESolved Spectroscopy) proton magnetic resonance spectroscopy ((1)H-MRS) acquisition of the anterior cingulate cortex (AC) in healthy human subjects. MATERIALS AND METHODS: AC (1)H-MRS measurements were performed in 15 healthy adult volunteers using a short echo PRESS sequence (GE Healthcare 3 Tesla, TE/TR = 30/2500 ms, 192 acquisitions, 6 cm(3) voxels). For each individual, a total of eight spectra were obtained during two identical scanning sessions separated by 3.5 h. In each, two consecutive AC spectra were acquired. After the first two scans, the subject left the scanner, then immediately returned for repositioning and acquisition of two more consecutive spectra. The subject then left the imaging centre to return 3.5 h later for a repeated procedure. Spectroscopic postprocessing was done using LCmodel. Interindividual, repositioning and time-of-day effects were measured using restricted maximum likelihood (REML) models of variance components analysis, where response variables were levels of creatine/phosphocreatine (Cr), N-acetyl-aspartate (NAA), myo-inositol (mI), choline (Cho), and the glutamate-glutamine complex (Glx). RESULTS: Interindividual effects were markedly higher than time-of-day and repositioning effects for all metabolites. CONCLUSION: Our findings show that (1)H-MRS measurements of the AC are sensitive to interindividual differences, while time of day and repositioning are markedly less important.