Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium.

BACKGROUND: Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity. METHODS: The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m2) and child sex were evaluated for effect modification. RESULTS: Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71-1.03) or ADHD (aOR 0.89; 95% CI, 0.76-1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55-0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80-1.18). CONCLUSIONS: In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.

The Challenge of Examining Social Determinants of Health in People Living With Tourette Syndrome.

BACKGROUND: To examine the association between race, ethnicity, and parental educational attainment on tic-related outcomes among Tourette Syndrome (TS) participants in the Tourette Association of America International Consortium for Genetics (TAAICG) database. METHODS: 723 participants in the TAAICG dataset aged ≤21 years were included. The relationships between tic-related outcomes and race and ethnicity were examined using linear and logistic regressions. Parametric and nonparametric tests were performed to examine the association between parental educational attainment and tic-related outcomes. RESULTS: Race and ethnicity were collapsed as non-Hispanic white (N=566, 88.0%) versus Other (N=77, 12.0%). Tic symptom onset was earlier by 1.1 years (P < 0.0001) and TS diagnosis age was earlier by 0.9 years (P = 0.0045) in the Other group (versus non-Hispanic white). Sex and parental education as covariates did not contribute to the differences observed in TS diagnosis age. There were no significant group differences observed across the tic-related outcomes in parental education variable. CONCLUSIONS: Our study was limited by the low number of nonwhite or Hispanic individuals in the cohort. Racial and ethnic minoritized groups experienced an earlier age of TS diagnosis than non-Hispanic white individuals. Tic severity did not differ between the two groups, and parental educational attainment did not affect tic-related outcomes. There remain significant disparities and gaps in knowledge regarding TS and associated comorbid conditions. Our study suggests the need for more proactive steps to engage individuals with tic disorders from all racial and ethnic minoritized groups to participate in research studies.

Temperament Traits in Pediatric Obsessive-Compulsive Disorder in Relation to Tourette Syndrome and Attention-Deficit Hyperactivity Disorder.

INTRODUCTION: Pediatric obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are often concurrent. This study explores the temperament profile of complex OCD phenotypes. METHODS: A clinical registry recorded demographic data, psychiatric diagnoses, and temperament traits, including novelty seeking (exploratory behaviors), harm avoidance (fear of uncertainty), reward dependence (sentimentality), and persistence (perseverance). Temperament data were accrued from the Junior Temperament and Character Inventory (JTCI). Participants were divided into (1) OCD only; (2) OCD+ADHD or TS; and (3) OCD+ADHD+TS to compare temperament. RESULTS: Participants include 126 youths with OCD (61.9% male, 88.9% white) between the ages 6 and 18 years (12.7 ± 3.1). Among the three groups, the complex neurodevelopmental disorder group OCD+ADHD+TS expresses the highest novelty seeking and lowest persistence. Harm avoidance is increased in all groups compared to reference controls, irrespective of concurrent ADHD or TS. For the OCD+ADHD+TS group, contamination and washing symptoms have higher novelty seeking (p < 0.01), while counting and ordering have lower novelty seeking (p < 0.05). Harm avoidance is increased with aggressive, somatic, and checking symptoms in OCD only (p < 0.01), while persistence is increased with repeating and counting symptoms in the comorbid groups (OCD+ADHD or TS, OCD+ADHD+TS). DISCUSSION/CONCLUSION: The complex subtype, OCD+ADHD+TS, is associated with high novelty seeking and low persistence, while high harm avoidance is linked to pediatric OCD irrespective of ADHD or TS co-occurrence. In sum, pediatric OCD with ADHD and TS confers a unique temperament profile, further refining complex phenotypes of pediatric OCD for future research.

Sex Differences in People with Tourette Syndrome and Persistent Motor or Vocal Tic Disorder in the Tourette Association of America International Consortium for Genetics Database.

Background and Objective: Tourette Syndrome (TS) and Persistent Motor or Vocal Tic Disorders (PMVT) are more prevalent in males (vs. females). Females with TS may have a delay in diagnosis, and more complex tic features (vs. males). With respect to comorbidities, obsessive-compulsive disorder (OCD) is more prevalent in females; attention-deficit hyperactivity disorder (ADHD) is more prevalent in males. Less is known about sex differences in PMVT. This study analyzes sex differences in outcomes among individuals with TS and PMVT in the Tourette Association of America International Consortium for Genetics dataset (TAAICG). Design/Methods: Data from 2403 individuals (N=2109 TS; N=294 PMVT) from the TAAICG were analyzed to explore the relationship between sex and TS or PMVT outcomes: age at tic onset; age at diagnosis; time-to-diagnosis; tic severity; and comorbidity rates. Regression models were adjusted for age and family relationships to examine the impact of sex on outcomes. Results: Females with TS (25.5% of the sample) had a later age of symptom onset (6.5±2.8 vs. 6.0±2.7; p=0.001), later age at diagnosis (13.3±11.2 vs. 10.7±8.1; p=0.0001), and a longer time-to-diagnosis [3 (1,7) vs. 2 (1,5), p=0.01] than males. The total Yale-Global Tic Severity Scale (YGTSS) was lower in females with TS (28.4±9.1 vs. 30.7±8.7); p<0.0001); OCD was slightly more prevalent in females (55% vs. 48.7%; p=0.01) although OCD severity did not differ by sex; ADHD was more prevalent in males (55.7% vs 38.9%; p<0.001). Females with TS had 0.46 lower odds of being diagnosed with TS (p<0.00001). Females with PMVT (42.9% of the sample) had an earlier age of symptom onset (7.9±3.3 vs. 8.9±3.7; p=0.05). Motor or vocal tic severity (YGTSS) was not significantly different. OCD, but not ADHD, was more prevalent in females (OCD: 41.9% vs. 22.2%; p<0.001: ADHD:16.5% vs 21.0%; p=0.4). Conclusion: Females with TS are less likely to be formally diagnosed and have a later age of symptom onset, later age at diagnosis, longer time-to-diagnosis, higher prevalence of OCD, and lower prevalence of ADHD (vs. males). Females with PMVT have an earlier age of symptom onset, higher prevalence of OCD, but similar ADHD prevalence rates (vs. males). Females with TS and PMVT may be clinically different than males with TS. Future research is needed to understand differences longitudinally in TS and PMVT.

Subtypes of Depressed Youth Admitted for Inpatient Psychiatric Care: A Latent Profile Analysis.

Depressed youth frequently present with comorbid symptoms. Comorbidity is related to a poorer prognosis, including treatment resistance, academic problems, risk of suicide, and overall impairment. Studies examining the latent structure of depression support the notion of multiple presentations of depressed youth; however, it is unclear how these presentations are represented among acutely impaired youth. Participants (n = 457) in this naturalistic study were admitted to a psychiatric inpatient unit (Mean age = 14.33 years, SD = 1.94;76% female;46.6% Black/African-American). Selected subscales from the parent-report Behavior Assessment System for Children, Second Edition, were utilized as indicators in a latent profile analysis. Subgroups were validated based on their relationships with meaningful clinical correlates (e.g., family factors, discharge diagnosis) and further described by their associations with demographic variables. A five-class model provided the best balance of fit and parsimony. Subtypes of depressed youth included Predominantly Depressed (39.1%), Oppositional (28.2%), Severely Disruptive (12.3%), Anxious-Oppositional (11.6%), and Anxious-Withdrawn (8.8%). Comorbid symptoms were present in four of the five classes (60.9% of sample). High levels of externalizing symptoms were a prominent clinical feature associated with three classes (52.1% of the sample). Construct validity of the respective classes was demonstrated by differential association with clinical correlates, family characteristics, and demographics. Findings suggest that depressed youth presenting for acute inpatient psychiatric care displayed varied clinical presentations. The identified latent groups aligned with existing research reflecting comorbidity with anxiety, inattention, and externalizing disorders. Findings underscore the need for an increased clinical appreciation of comorbidity and encourage more targeted and effective prevention and treatment strategies.

Caregiver-reported psychological and behavioural functioning of children with suicidal thoughts and behaviour: A case-control design.

OBJECTIVE: This exploratory project aims to provide an empirical understanding of the caregiver-reported emotional and behavioural functioning of children 12 and under who present to an inpatient psychiatric unit with suicidal ideation and/or attempts. METHOD: A retrospective chart review was conducted, including all patients (n = 573) aged 12 and under admitted to a psychiatric inpatient unit between September 2011-December 2015 for suicidal ideation without proximal attempt (n = 155) or a suicide attempt (n = 37). Inpatients without suicidal thoughts and behaviour in the same age range (n = 381) served as a control group. The three groups were compared on a range of variables, including patient history/demographics, caregiver-reported emotional/behavioural functioning, and discharge diagnoses. RESULTS: Children who were admitted to a psychiatric inpatient unit following suicide attempts and/or ideation demonstrated clinically significant levels of externalizing and internalizing symptoms. Children with suicidal thoughts and behaviour (STB) were more likely to be female and older than their peers without STB, more likely to report a history of sexual abuse and non-suicidal self-injury, and to be diagnosed with a depressive disorder. CONCLUSIONS: Children with STB differ demographically, symptomatically, and diagnostically from their peers without STB with comparable levels of psychiatric impairment (i.e., necessitating inpatient admission). Results provide provisional information on this concerning group of children, which can be used to aid identification of risk factors, inform treatment, and stimulate future work.

Prevalence and correlates of lifetime suicide attempt in obsessive-compulsive disorder with major depression.

BACKGROUND: Little is known about specific obsessive-compulsive clinical features associated with lifetime history of suicide attempt in individuals with obsessive-compulsive disorder (OCD) and major depression. METHODS: The study sample included 515 adults with OCD and a history of major depression. In exploratory analyses, we compared the distributions of demographic characteristics and clinical features in those with and without a history of attempted suicide and used logistic regression to evaluate the association between specific obsessive-compulsive clinical features and lifetime suicide attempt. RESULTS: Sixty-four (12%) of the participants reported a lifetime history of suicide attempt. Those who had attempted suicide were more likely to report having experienced violent or horrific images (52% vs. 30%; p < 0.001). The odds of lifetime suicide attempt were more than twice as great in participants with versus without violent or horrific images (O.R. = 2.46, 95%, CI = 1.45-4.19; p < 0.001), even after adjustment for other risk correlates of attempted suicide, including alcohol dependence, post-traumatic stress disorder, parental conflict, excessive physical discipline, and number of episodes of depression. The association between violent or horrific images and attempted suicide was especially strong in men, 18-29 year olds, those with post-traumatic stress disorder, and those with particular childhood adversities. CONCLUSIONS: Violent or horrific images are strongly associated with lifetime suicide attempts in OCD-affected individuals with a history of major depression. Prospective clinical and epidemiological studies are needed to elucidate the basis of this relationship.

Exome sequencing in obsessive-compulsive disorder reveals a burden of rare damaging coding variants.

Obsessive-compulsive disorder (OCD) affects 1-2% of the population, and, as with other complex neuropsychiatric disorders, it is thought that rare variation contributes to its genetic risk. In this study, we performed exome sequencing in the largest OCD cohort to date (1,313 total cases, consisting of 587 trios, 41 quartets and 644 singletons of affected individuals) and describe contributions to disease risk from rare damaging coding variants. In case-control analyses (n = 1,263/11,580), the most significant single-gene result was observed in SLITRK5 (odds ratio (OR) = 8.8, 95% confidence interval 3.4-22.5, P = 2.3 × 10-6). Across the exome, there was an excess of loss of function (LoF) variation specifically within genes that are LoF-intolerant (OR = 1.33, P = 0.01). In an analysis of trios, we observed an excess of de novo missense predicted damaging variants relative to controls (OR = 1.22, P = 0.02), alongside an excess of de novo LoF mutations in LoF-intolerant genes (OR = 2.55, P = 7.33 × 10-3). These data support a contribution of rare coding variants to OCD genetic risk.

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

BACKGROUND: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. OBJECTIVE: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. METHODS: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature. RESULTS: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. CONCLUSIONS: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Use of Electroconvulsive Therapy in Autism.

The mechanism of action of electroconvulsive therapy (ECT) is not fully elucidated, with prevailing theories ranging from neuroendocrinological to neuroplasticity effects of ECT or epileptiform brain plasticity. Youth with autism can present with catatonia. ECT is a treatment that can safely and rapidly resolve catatonia in autism and should be considered promptly. The literature available for ECT use in youth with autism is consistently growing. Under-recognition of the catatonic syndrome and delayed diagnosis and implementation of the anticatatonic treatment paradigms, including ECT, as well as stigma and lack of knowledge of ECT remain clinical stumbling blocks.

Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Repetitive and Self-injurious Behaviors in Children with Cornelia de Lange Syndrome.

Cornelia de Lange syndrome (CdLS) is associated with repetitive and self-injurious behaviors (RBs, SIB). Evaluating children with CdLS, this study: (1) characterizes the spectrum of RBs; (2) characterizes the impact and severity of RBs including SIB; (3) describes how age and adaptive functioning relate to RBs including SIB. Fifty children (5-17 years) with CdLS were assessed with Children's Yale-Brown Obsessive Compulsive Scale Modified for PDD; Aberrant Behavior Checklist (ABC); Vineland Adaptive Behaviors Scales (VABS). All children had ≥ 1 type of RB; 44% had some form of SIB. 64% spent > 1 h/day displaying RBs. Lower VABS adaptive functioning was associated with higher stereotypy and SIB scores (ABC). In children with CdLS, RBs including SIB are common, impactful, and associated with lower adaptive functioning.

Use of Electroconvulsive Therapy in Autism.

The mechanism of action of electroconvulsive therapy (ECT) is not fully elucidated, with prevailing theories ranging from neuroendocrinological to neuroplasticity effects of ECT or epileptiform brain plasticity. Youth with autism can present with catatonia. ECT is a treatment that can safely and rapidly resolve catatonia in autism and should be considered promptly. The literature available for ECT use in youth with autism is consistently growing. Under-recognition of the catatonic syndrome and delayed diagnosis and implementation of the anticatatonic treatment paradigms, including ECT, as well as stigma and lack of knowledge of ECT remain clinical stumbling blocks.

Risk Factors for Seclusion in Children and Adolescents Inpatient Psychiatry: The Role of Demographic Characteristics, Clinical Severity, Life Experiences and Diagnoses.

OBJECTIVE: To understand the risk factors for seclusion in a sample of children and adolescents admitted to an inpatient psychiatry unit looking at demographic, clinical severity, life experience, and diagnostic characteristics. METHODS: An unmatched case-control retrospective analysis of psychiatric records in a pediatric inpatient unit from December 2011 to December 2015 (N = 1986) RESULTS: Individual characteristics, including demographics, clinical severity, and clinical presentation as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) jointly predicted seclusion in adolescents, with younger age, male sex, black race, having a prior admission, and having a disruptive behavior or bipolar and related disorder diagnoses being predictive of seclusion. While demographic and clinical severity factors were predictive of seclusion in multivariate models, clinical diagnoses only added modestly to the variance explained. CONCLUSIONS: High-risk demographic and clinical characteristics for seclusion events in children and adolescents can provide valuable information to guide interventions to prevent seclusion events during their hospitalization.

Hydrogen sulfide: a target to modulate oxidative stress and neuroplasticity for the treatment of pathological anxiety.

Introduction: Anxiety disorders result inhigh patient burden and utilization of healthcare resources. Evidence-based treatments for pathological anxiety include targeted psychotherapy and use of serotonin-augmenting agents. Limitations in access to cognitive behavioral therapy and potential disadvantages to the use of psychotropics make the need for novel approaches to therapeutics for pathological anxiety salient.Areas Covered: Neuroplasticity mechanisms, as well as managing oxidative stress and inflammatory cellular allostatic loads can decrease anxiety. The gasotransmitter hydrogen sulfide (H2S) can impact these mechanisms through a) maintaining intracellular reduced glutathione in the CNS to decrease oxidative stress; b) facilitating neuroplasticity in amygdalar regions via the 2B subunit of n-methyl-d-aspartate (NMDA) receptors, in conjunction with the cAMP messenger system and a CNS kinase, PKC-γ; and c) regulating intracellular Ca2+ homeostasis in neurons and glial cells, among others.Expert Opinion: Given the mounting evidence for the role of H2S in neuronal health and its potential to decrease pathological anxiety, the current challenge in H2S therapeutics remains finding an efficient delivery system of this gasotransmitter in a reliable, safe and nontoxic form to engage in clinical trials. Current efforts include H2S-delivering moieties attached to known drugs, natural sulfide-releasing compounds such as garlic, and the regulation of dysfunctional breathing through breathing retraining.

General personality dimensions, impairment and treatment response in obsessive-compulsive disorder.

General personality dimensions are associated with clinical severity and treatment response in individuals with depression and many anxiety disorders, but little is known about these relationships in individuals with obsessive-compulsive disorder (OCD). Individuals in the current study included 705 adults with OCD who had participated in family and genetic studies of the disorder. Participants self-completed the Neuroticism, Extraversion, Openness Personality Inventory or Neuroticism, Extraversion, Openness Five-Factor Inventory-3. Relationships between personality scores, and subjective impairment and OCD treatment response, were evaluated. The odds of subjective impairment increased with (unit increase in) the neuroticism score (odds ratio, OR = 1.03; 95% CI = 1.01-1.04; p < 0.01) and decreased with extraversion scores (OR = 0.98; 95% CI = 0.96-0.99; p < 0.01). The odds of reporting a good response to serotonin/selective serotonin reuptake inhibitors (OR = 1.02; 95% CI = 1.01-1.04; p < 0.01) or cognitive behavioural therapy (OR = 1.03; 95% CI = 1.01-1.05; p < 0.01) increased with the extraversion score. The magnitude of these relationships did not change appreciably after adjusting for other clinical features related to one or more of the personality dimensions. The findings suggest that neuroticism and extraversion are associated with subjective impairment, and that extraversion is associated with self-reported treatment response, in individuals with OCD. © 2019 John Wiley & Sons, Ltd.

Trichotillomania comorbidity in a sample enriched for familial obsessive-compulsive disorder.

BACKGROUND: This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (n = 2606) enriched for familial obsessive-compulsive disorder (OCD), to inform TTM classification. METHODS: We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and the OCD Collaborative Genetics Study, a six-site genetic linkage study of OCD (487 families). We used logistic regression (with generalized estimating equations) to assess the strength of associations between TTM and other DSM-IV disorders. RESULTS: TTM had excess comorbidity with a number of conditions from different DSM-IV chapters, including tic disorders, alcohol dependence, mood disorders, anxiety disorders, impulse-control disorders, and bulimia nervosa. However, association strengths (odds ratios) were highest for kleptomania (6.6), pyromania (5.8), OCD (5.6), skin picking disorder (4.4), bulimia nervosa (3.5), and pathological nail biting (3.4). CONCLUSIONS: TTM is comorbid with a number of psychiatric conditions besides OCD, and it is strongly associated with other conditions involving impaired impulse control. Though DSM-5 includes TTM as an OCD-related disorder, its comorbidity pattern also emphasizes the impulsive, appetitive aspects of this condition that may be relevant to classification.

Evidence-based treatment of Tourette's disorder and chronic tic disorders.

Introduction: Chronic Tic Disorders and Tourette's Disorder (collectively referred to as TD) are characterized by sudden, rapid, and repetitive motor movements or vocalizations called tics. Children, adolescents, and adults with TD often experience co-occurring psychiatric symptoms and impairments in multiple domains. As a result of tics and other symptoms, patients with TD can develop negative self-views, require considerable accommodations, and experience a poor quality of life. Therefore, the efficient and effective management of TD bears considerable importance. Areas covered: This expert review evaluated the empirical support for behavioral and pharmacological interventions based on the results of randomized controlled trials (RCTs). Behavioral interventions evaluated include habit reversal training (HRT), comprehensive behavioral intervention for tics (CBIT), and exposure response prevention (ERP). Reviewed pharmacological interventions included alpha-2 agonists, antipsychotics, and anticonvulsants. Expert opinion: This review identified several efficacious behavioral and pharmacological interventions for TD. However, several gaps in the management of TD include: (1) the access/availability of behavioral interventions, (2) novel and more efficacious treatment approaches, and (3) the development of more comprehensive interventions to manage TD. In order to advance the treatment of TD, additional research is necessary to efficiently, effectively, and comprehensively develop and evaluate new treatments for patients with TD.

Immune-Related Comorbidities in Childhood-Onset Obsessive Compulsive Disorder: Lifetime Prevalence in the Obsessive Compulsive Disorder Collaborative Genetics Association Study.

Objective: To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives. Methods: Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Genetics Association Study. Lifetime prevalence of immune-related diseases was compared with the highest available population estimate and reported as a point estimate with 95% adjusted Wald interval. Worst-episode OCD severity and symptom dimensions were assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Symptom Checklist (YBOCS-CL). Results: Probands reported higher-than-expected prevalence of scarlet fever (4.0 [3.1-5.2]% vs. 1.0%-2.0%, z = 1.491, p < 0.001, n = 1389), encephalitis or meningitis (1.4 [0.9-2.1]% vs. 0.1%-0.4%, z = 5.913, p < 0.001, n = 1393), rheumatoid arthritis (1.1 [0.6-2.0]% vs. 0.2%-0.4%, z = 3.416, p < 0.001, n = 949) and rheumatic fever (0.6 [0.3-1.2]% vs. 0.1%-0.2%, z = 3.338, p < 0.001, n = 1390), but not systemic lupus erythematosus, diabetes, asthma, multiple sclerosis, psoriasis, or inflammatory bowel disease. First-degree relatives reported similarly elevated rates of scarlet fever, rheumatic fever, and encephalitis or meningitis independent of OCD status. There was no association between worst-episode severity and immune-related comorbidities, although probands reporting frequent ear or throat infections had increased severity of cleaning-/contamination-related symptoms (mean factor score 2.5 ± 0.9 vs. 2.3 ± 1.0, t = 3.183, p = 0.002, n = 822). Conclusion: These data suggest high rates of streptococcal-related and other immune-mediated diseases in patients with childhood-onset OCD and are consistent with epidemiological studies in adults noting familial clustering. Limitations include potential reporting bias and absence of a control group, underscoring the need for further prospective studies characterizing medical and psychiatric disease clusters and their interactions in children. Such studies may ultimately improve our understanding of OCD pathogenesis and aid in the development of adjunctive immune-modulating therapeutic strategies.