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.

Psychiatric comorbidity in the Baltimore ECA follow-up study: the matrix approach.

BACKGROUND: Psychiatric comorbidity is defined as the joint occurrence of two or more mental or substance use disorders. Widespread psychiatric comorbidity has been reported in treatment and population-based studies. The aim of this study was to measure the extent and impact of psychiatric comorbidity in a cohort of the Baltimore Epidemiologic Catchment Area study. METHODS: We examined the comorbidity burden of 16 mental disorders in a cohort of 847 participants using both established and novel analytical approaches The Comorbidity to Diagnosis Inflation Ratio (CDIR), is a statistical instrument that quantifies impact of pairwise comorbid associations, both on the whole sample, as well as on each specific disorder. RESULTS: Most anxiety disorders had substantial co-occurrence with each other, as well as with Major Depressive Disorder (MDD). In addition, mood disorders had a high degree of comorbidity with Alcohol Dependence (AD). The CDIR for the whole sample was 1.32, indicating a ratio of 132 comorbidities per 100 diagnoses. The conditions with high sample prevalence were relatively less comorbid than the low prevalence conditions. Obsessive Compulsive Disorder had a comorbidity burden that was 89% greater than the overall sample. CONCLUSION: Anxiety disorders are highly interrelated, as well as highly comorbid with depression. The comorbidity phenomenon is linked to the differential prevalence of the analyzed conditions. Comorbidity frequency (most prevalent comorbid condition) appears mutually exclusive to comorbidity burden (most widely interrelated condition). While AD and MDD were the most frequently diagnosed disorders; low prevalence conditions as OCD and GAD were the most widely interrelated.

An investigation of COVID-19 related worry in a United States population sample.

BACKGROUND: Although general anxiety has increased markedly since the onset of the COVID-19 pandemic, little has been reported about the demographic distribution of COVID-19 related worry, its relationship with psychological features, and its association with depression symptoms in the United States (US). METHODS: 2117 participants, selected to represent the age, gender, and race/ethnic distributions of the US population, completed an online survey. Analysis of variance and correlation analyses were used to assess relationships between the COVID-19 related worry score and demographic characteristics, past psychiatric diagnoses, personality dimensions, and current psychological symptoms. Logistic regression was used to evaluate the association between the COVID-19 worry score and depression symptoms. RESULTS: The COVID-19 worry score was markedly higher in younger (18-49 year-olds) than older participants, and moderately higher in men, those who were married or cohabiting, with post-college education, and/or living in large urban areas. The COVID-19 worry score also was markedly higher in those who reported having been diagnosed with a psychiatric disorder. The COVID-19 worry score correlated with neuroticism, current psychological symptoms, and COVID-19 risk and COVID-19 behavior scores. The COVID-19 worry score was associated with current depression symptoms (OR = 1.10, 95% CI = 1.09-1.11; p < 0.001) in univariable models and remained significant after adjustment for other correlates of depression, including COVID-19 risk. CONCLUSIONS: In this US sample, the COVID-19 worry score was inversely related to age, strongly related to psychological symptoms, and independently associated with depression symptoms. These findings have implications for the community mental health response to the COVID-19 pandemic in the US.

Neural correlates of doubt in decision-making.

The experience of doubt, the lack of confidence in one's perceptions, internal states, memory and attention, can be due to the variability in occurrence of a phenomenon or can be driven by the internal experience of uncertainty based on subjective evaluation of the environment. Although the experience of some doubt is adaptive in normal cognitive functioning, excessive doubt can significantly impair decision-making and in extreme cases give rise to psychopathology. Although neuroimaging studies have provided some insight into the network of brain areas that is engaged when decision-making involves uncertainty, it remains unclear if dysfunction in these areas also gives rise to the experience and pathological expression of doubt. This study examined the neural correlates of doubt using neuroimaging during the performance of a forced-choice perceptual decision-making task under varying levels of uncertainty in participants who reported either low or high doubt. Participants reporting high doubt exhibited increased activation in the bilateral inferior parietal lobule (IPL) during perceptual decision-making which was not observed in participants who reported low doubt. Furthermore, activity in the IPL in high doubt participants was associated with clinical measures of doubt and showed functional connectivity differences between the high and low doubt groups. The findings of the current study suggest a key role of the IPL and provide a network of brain regions that may play a role in the experience and expression of doubt.

Long-term physical health outcomes of obsessive-compulsive personality disorder traits.

BACKGROUND: Obsessive-compulsive personality disorder (OCPD) is characterized by pervasive and persistent traits including preoccupation with orderliness, perfectionism, and control. Relatively little is known about the potential relationship between OCPD traits and physical health. METHODS: We investigated the association between OCPD traits and several self-reported medical conditions in 249 individuals followed prospectively from 1981 until 2004/2005 as part of the Epidemiological Catchment Area. RESULTS: The OCPD trait score was inversely related to hypertension in males, in models unadjusted (OR = 0.66; 95% CI, 0.45-0.90) and adjusted (OR = 0.70; 95% CI, 0.47-0.95) for sociodemographic variables. Perfectionism was inversely related to hypertension in the unadjusted models for men (OR = 0.34; 95% CI, 0.12-0.89). Indecisiveness was positively associated with heart conditions in adjusted models for women (OR = 3.46; 95% CI, 1.11-10.52). CONCLUSION: OCPD traits are associated with cardiovascular health in both sexes. Further studies are needed to understand the specificity of these relationships, as well as to determine the underlying mechanism.

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.

Peripartum complications associated with obsessive compulsive disorder exacerbation during pregnancy.

Prior research has shown that onset or exacerbation of OCD is associated with menstruation, pregnancy, and the post-partum period. However, the underlying cause is unclear. The goal of this study was to assess whether pregnancy and birth complications were associated with OCD symptoms exacerbation, among women with established OCD. Two-hundred and five (n=205) women with OCD retrospectively reported information on their physical and mental health during their first pregnancy. Over a third of the sample (34%) reported an exacerbation in their OCD symptoms. History of pregnancy and birth complications in the first pregnancy were similar between women who did and did not experience symptom exacerbation, with the exception of gestational diabetes, which was significantly more common among women who experienced exacerbation (7% vs 1%, p=0.03). In a multivariable logistic regression model, gestational diabetes remained significantly associated with exacerbation of OCD symptoms (OR=8.44 [95% CI 1.37-77.27]; p=0.03), even after adjusting for maternal age, OCD severity and treatment, premenstrual OCD symptom increase, stress during pregnancy, and major depression or anxiety disorder diagnosis during pregnancy. We discuss potential explanations for this link. These findings should be treated as hypothesis-generating and need to be replicated in a larger, prospective study.

Contamination-related behaviors, obsessions, and compulsions during the COVID-19 pandemic in a United States population sample.

BACKGROUND: Contamination-prevention behaviors such as mask wearing and physical distancing are crucial to reduce coronavirus transmission during the COVID-19 pandemic. We hypothesized that engagement in these behaviors could provoke obsessions and phobias in vulnerable individuals in the community. METHODS: A total of 2117 participants, systematically selected to represent the age, gender, and race distributions of the US population, completed an online survey that assessed demographic characteristics, clinical features, COVID-19 risks, and COVID-19 contamination-prevention behaviors. Logistic regression was used to estimate the magnitude of the relationships between the COVID-19 behavior score and clinically significant contamination obsessions, contamination compulsions, and pre-COVID-19 to current change in obsessive-compulsive symptom scores. RESULTS: The COVID-19 behavior score was significantly associated with contamination obsessions (odds ratio (OR) = 1.15, 95% CI = 1.12-1.16; p < 0.001) and contamination phobias (OR = 1.14, 95% CI = 1.12-1.16; p < 0.001). The COVID-19 behavior score also was associated with pre-pandemic to current increase in the overall obsessive-compulsive symptom score (OR = 1.16, 95% CI = 1.09-1.23; p < 0.001), as well as increase in obsessive-compulsive symptom score excluding washing items (OR = 1.13, 95% CI = 1.07-1.19; p < 0.001). The magnitude of these relationships did not appreciably change, after adjustment for other variables associated with the outcomes. Moreover, the relationship was significant in those with or without OCD, and in individuals with different levels of doubt and COVID-19 risk. CONCLUSIONS: Contamination safety measures are critical for reducing the spread of COVID-19 in the community. However, they may be related to the development of contamination-related symptoms and OCD in vulnerable individuals, complicating the diagnosis and treatment of mental disorders during this period.

The serotonin transporter gene polymorphism (SLC6A4) and risk for psychiatric morbidity and comorbidity in the Baltimore ECA follow-up study.

BACKGROUND: The human serotonin transporter (SERT) gene polymorphism (5HTTLPR) has been associated with multiple psychiatric disorders, including major depression, anxiety disorders, and substance use disorders. This study investigated the association between 5HTTLPR and psychiatric morbidity and comorbidity in a psychiatrist-examined population sample. METHODS: 628 participants, mean age 48.3 years old, were assessed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry. Associations between 5HTTLPR and the prevalence, comorbidity, and time-to-diagnoses for 16 psychiatric conditions were evaluated, using several analytical approaches. RESULTS: The SERT S allele was significantly associated with an increased lifetime prevalence of panic disorder. There was a "protective" association between SERT gene S allele carrier status and the risk of obsessive-compulsive disorder (OCD) in time-to-event analysis. Carriers of the S allele had a significant increased risk of two specific comorbid disorder pairs: major depressive disorder (MDD) and social phobia, and MDD and agoraphobia. Overall, there was no increased risk of receiving an initial or an additional diagnosis for a mental disorder in the SERT S allele carriers CONCLUSIONS: The findings suggest that the S allele carrier status is associated with an increased prevalence of panic disorder in a community sample. There was an increased risk for comorbidity in a more homogeneous subgroup of cases with MDD and social phobia, as well as or agoraphobia. Our findings suggest a specific effect of the SERT promoter gene polymorphism on a subgroup of individuals identifiable by their comorbidity.

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.

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.

Validating a dimension of doubt in decision-making: A proposed endophenotype for obsessive-compulsive disorder.

Doubt is subjective uncertainty about one's perceptions and recall. It can impair decision-making and is a prominent feature of obsessive-compulsive disorder (OCD). We propose that evaluation of doubt during decision-making provides a useful endophenotype with which to study the underlying pathophysiology of OCD and potentially other psychopathologies. For the current study, we developed a new instrument, the Doubt Questionnaire, to clinically assess doubt. The random dot motion task was used to measure reaction time and subjective certainty, at varying levels of perceptual difficulty, in individuals who scored high and low on doubt, and in individuals with and without OCD. We found that doubt scores were significantly higher in OCD cases than controls. Drift diffusion modeling revealed that high doubt scores predicted slower evidence accumulation than did low doubt scores; and OCD diagnosis lower than controls. At higher levels of dot coherence, OCD participants exhibited significantly slower drift rates than did controls (q<0.05 for 30%, and 45% coherence; q<0.01 for 70% coherence). In addition, at higher levels of coherence, high doubt subjects exhibited even slower drift rates and reaction times than low doubt subjects (q<0.01 for 70% coherence). Moreover, under high coherence conditions, individuals with high doubt scores reported lower certainty in their decisions than did those with low doubt scores. We conclude that the Doubt Questionnaire is a useful instrument for measuring doubt. Compared to those with low doubt, those with high doubt accumulate evidence more slowly and report lower certainty when making decisions under conditions of low uncertainty. High doubt may affect the decision-making process in individuals with OCD. The dimensional doubt measure is a useful endophenotype for OCD research and could enable computationally rigorous and neurally valid understanding of decision-making and its pathological expression in OCD and other disorders.

Genetics of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been seen to run in families and genetics help to understand its heritability. In this review, we summarize older studies which focused on establishing the familial nature of OCD, including its various dimensions of symptoms, and we focus on recent findings from studies using both the candidate gene approach and genome-wide association study (GWAS) approach. The family studies and twin studies establish the heritability of OCD. Candidate gene approaches have implicated genes in the serotonergic, glutamatergic, and dopaminergic pathways. GWAS has not produced significant results possibly due to the small sample size. Newer techniques such as gene expression studies in brain tissue, stem cell technology, and epigenetic studies may shed more light on the complex genetic basis of OCD.

Antisocial personality and risks of cause-specific mortality: results from the Epidemiologic Catchment Area study with 27 years of follow-up.

PURPOSE: Little is known about the effect of antisocial personality disorder (ASPD) on the risks of cause-specific mortality in the community. This study aimed to close this gap by evaluating if ASPD increases risks of cause-specific mortality in population-based residential and institutionalized samples with 27 years of follow-up. METHODS: Data were collected in four metropolitan sites as part of the Epidemiologic Catchment Area (ECA) study during 1979-1983. Records were linked to the National Death Index through the end of 2007. Cox proportional hazards models adjusted for propensity weights and sample weights were fitted to estimate the effect of ASPD on the hazard of dying. RESULTS: 420 respondents with ASPD (median survival age 71.0 years) and 15,367 without ASPD (median survival age 84.6 years) were included in this study. Those with ASPD were more likely to die from all causes (HR = 4.46; 95% CI = 2.44-8.16), suicide (HR = 2.81; 95% CI = 1.03-7.65), malignant neoplasms (HR = 4.09; 95% CI = 2.66-6.28), chronic lower respiratory disease (HR = 5.67; 95% CI = 2.92-11.0), and human immunodeficiency virus infection (HR = 8.07; 95% CI = 2.03-32.1), but not from accidents (HR = 0.58; 95% CI = 0.17-1.93) or heart disease (HR = 1.09; 95% CI = 0.43-2.76). CONCLUSIONS: Our findings demonstrate that antisocial personality disorder is a strong predictor of all-cause mortality, and cause-specific mortality. Early identification, treatment, and prevention of ASPD are important public mental health initiatives that could reduce premature mortality among this vulnerable population.

Self-reported executive function and hoarding in adults with obsessive-compulsive disorder.

BACKGROUND: Hoarding behavior may distinguish a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Little is known about the relationship between executive dysfunction and hoarding in individuals with OCD. METHODS: The study sample included 431 adults diagnosed with DSM-IV OCD. Participants were assessed by clinicians for Axis I disorders, personality disorders, indecision, and hoarding. Executive functioning domains were evaluated using a self-report instrument, the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). We compared scores on these domains in the 143 hoarding and 288 non-hoarding participants, separately in men and women. We used logistic regression to evaluate relationships between executive function scores and hoarding, and correlation and linear regression analyses to evaluate relationships between executive function scores and hoarding severity, in women. RESULTS: In men, the hoarding group had a significantly higher mean score than the non-hoarding group only on the shift dimension. In contrast, in women, the hoarding group had higher mean scores on the shift scale and all metacognition dimensions, i.e., those that assess the ability to systematically solve problems via planning and organization. The relationships in women between hoarding and scores on initiating tasks, planning/organizing, organization of materials, and the metacognition index were independent of other clinical features. Furthermore, the severity of hoarding in women correlated most strongly with metacognition dimensions. CONCLUSIONS: Self-reported deficits in planning and organization are associated with the occurrence and severity of hoarding in women, but not men, with OCD. This may have implications for elucidating the etiology of, and developing effective treatments for, hoarding in OCD.

Genome Wide Association Study (GWAS) between Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD).

Objective: The aim of this study was to identify any potential genetic overlap between attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). We hypothesized that since these disorders share a sub-phenotype, they may share common risk alleles. In this manuscript, we report the overlap found between these two disorders. Methods: A meta-analysis was conducted between ADHD and OCD, and polygenic risk scores (PRS) were calculated for both disorders. In addition, a protein-protein analysis was completed in order to examine the interactions between proteins; p-values for the protein-protein interaction analysis was calculated using permutation. Conclusion: None of the single nucleotide polymorphisms (SNPs) reached genome wide significance and there was little evidence of genetic overlap between ADHD and OCD.

C9orf72 hexanucleotide repeat expansions are not a common cause of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a polygenic neuropsychiatric disorder characterized by repetitive thoughts and behaviors that cause distress. The pathogenic repeat expansion [GGGGCC]n found at the C9orf72 locus is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and has also been documented in patients with psychosis and schizophrenia. Furthermore, obsessions and compulsions have been identified in patients diagnosed with ALS and/or FTD and carrying the pathogenic repeat expansion. Here, we performed genetic screening for the C9orf72 repeat expansion on 573 patients diagnosed with OCD. None of the patients were found to carry the expansion. The results show that patients with OCD do not commonly carry the pathogenic repeat expansion and therefore should not be routinely screened. OCD and psychotic patients who do test positive for the C9orf72, however, should be closely observed for the later development of FTD and ALS.