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.

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.

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.

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.

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.

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.

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.

An investigation of doubt in obsessive-compulsive disorder.

BACKGROUND: Clinicians have long considered doubt to be a fundamental characteristic of obsessive-compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been addressed. METHODS: Participants included 1182 adults with OCD who had participated in family and genetic studies of OCD. We used a clinical measure of the severity of doubt, categorized as none, mild, moderate, severe, or extreme. We evaluated the relationship between doubt and OCD clinical features, Axis I disorders, personality and personality disorder dimensions, impairment, and treatment response. RESULTS: The severity of doubt was inversely related to the age at onset of OCD symptoms. Doubt was strongly related to the number of checking symptoms and, to a lesser extent, to the numbers of contamination/cleaning and hoarding symptoms. Doubt also was related to the lifetime prevalence of recurrent major depression and generalized anxiety disorder; to the numbers of avoidant, dependent, and obsessive-compulsive personality disorder traits; and to neuroticism and introversion. Moreover, doubt was strongly associated with global impairment and poor response to cognitive behavioral treatment (CBT), even adjusting for OCD severity and other correlates of doubt. CONCLUSIONS: Doubt is associated with important clinical features of OCD, including impairment and cognitive-behavioral treatment response.

Parental bonding and hoarding in obsessive-compulsive disorder.

BACKGROUND: Hoarding behavior may indicate a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Empirical evidence supports a relationship between hoarding and emotional over-attachment to objects. However, little is known about the relationship between hoarding and parental attachment in OCD. METHOD: The study sample included 894 adults diagnosed with DSM-IV OCD who had participated in family and genetic studies of OCD. Participants were assessed for Axis I disorders, personality disorders, and general personality dimensions. The Parental Bonding Instrument (PBI) was used to assess dimensions of perceived parental rearing (care, overprotection, and control). We compared parental PBI scores in the 334 hoarding and 560 non-hoarding participants, separately in men and women. We used logistic regression to evaluate the relationship between parenting scores and hoarding in women, adjusting for other clinical features associated with hoarding. RESULTS: In men, there were no significant differences between hoarding and non-hoarding groups in maternal or paternal parenting scores. In women, the hoarding group had a lower mean score on maternal care (23.4 vs. 25.7, p<0.01); a higher mean score on maternal protection (9.4 vs. 7.7, p<0.001); and a higher mean score on maternal control (7.0 vs. 6.2, p<0.05), compared to the non-hoarding group. The magnitude of the relationships between maternal bonding dimensions and hoarding in women did not change after adjustment for other clinical features. Women who reported low maternal care/high maternal protection had significantly greater odds of hoarding compared to women with high maternal care/low maternal protection (OR=2.54, 95% CI=1.60-4.02, p<0.001). CONCLUSIONS: Perceived poor maternal care, maternal overprotection, and maternal overcontrol are associated with hoarding in women with OCD. Parenting dimensions are not related to hoarding in men. These findings provide further support for a hoarding subtype of OCD and for sex-specific differences in etiologic pathways for hoarding in OCD.

Doubt and the decision-making process in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) is based on the presence of specific symptoms and their consequence in the lives of those that exhibit them. It is likely that these symptoms emerge from a neurocognitive vulnerability in the mental life of the individual which has a basis in neurophysiology. The prominence of doubt/uncertainty/lack of confidence (These terms are used interchangeably in this paper.), in the clinical presentation of many patients suffering from OCD leads to our consideration of the cognitive basis for this phenomenon. In this paper, we propose that OCD emerges from a perturbation in the decision-making process. Specifically, we hypothesize that there is diminished confidence, conviction, or certainty with regard to assimilating the information necessary to reach a decision. Recent advances in the neuroscience of decision-making provide an opportunity to further our understanding of the vulnerability underlying OCD.

ADHD and executive functioning deficits in OCD youths who hoard.

Hoarding is common among youth with obsessive compulsive disorder (OCD), with up to 26% of OCD youth exhibiting hoarding symptoms. Recent evidence from adult hoarding and OCD cohorts suggests that hoarding symptoms are associated with executive functioning deficits similar to those observed in subjects with attention deficit hyperactivity disorder (ADHD). However, while hoarding behavior often onsets during childhood, there is little information about executive function deficits and ADHD in affected children and adolescents. The study sample included 431 youths (ages 6-17 years) diagnosed with OCD who participated in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study and completed a series of clinician-administered and parent report assessments, including diagnostic interviews and measures of executive functioning (Behavior Rating Inventory of Executive Functioning; BRIEF) and hoarding severity (Hoarding Rating Scale-Interview; HRS-I). 113 youths (26%) had clinically significant levels of hoarding compulsions. Youths with and without hoarding differed significantly on most executive functioning subdomains and composite indices as measured by the parent-rated BRIEF. Groups did not differ in the frequency of full DSM-IV ADHD diagnoses; however, the hoarding group had significantly greater number of inattention and hyperactivity symptoms compared to the non-hoarding group. In multivariate models, we found that overall BRIEF scores were related to hoarding severity, adjusting for age, gender and ADHD symptoms. These findings suggest an association between hoarding and executive functioning deficits in youths with OCD, and assessing executive functioning may be important for investigating the etiology and treatment of children and adolescents with hoarding and OCD.