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.

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.

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.

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.

Obsessive-compulsive disorder and female reproductive cycle events: results from the OCD and reproduction collaborative study.

BACKGROUND: Women with obsessive-compulsive disorder (OCD) often report that symptoms first appear or exacerbate during reproductive cycle events; however, little is known about these relationships. The goals of this study were to examine, in a US and a European female OCD sample, onset and exacerbation of OCD in reproductive cycle events, and to investigate the likelihood of repeat exacerbation in subsequent pregnancies and postpartum periods. METHODS: Five hundred forty-two women (United States, n = 352; Dutch, n = 190) who met DSM-IV criteria for OCD, completed self-report questionnaires designed to assess OCD onset and symptom exacerbation associated with reproductive events. RESULTS: OCD onset occurred within 12 months after menarche in 13.0%, during pregnancy in 5.1%, at postpartum in 4.7%, and at menopause in 3.7%. Worsening of pre-existing OCD was reported by 37.6% of women at premenstruum, 33.0% during pregnancy, 46.6% postpartum, and 32.7% at menopause. Exacerbation in first pregnancy was significantly associated with exacerbation in second pregnancy (OR = 10.82, 95% CI 4.48-26.16), as was exacerbation in first postpartum with exacerbation in second postpartum (OR = 6.86, 95% CI 3.27-14.36). Results were replicated in both samples. CONCLUSIONS: Reproductive cycle events are periods of increased risk for onset and exacerbation of OCD in women. The present study is the first to provide significant evidence that exacerbation in or after first pregnancy is a substantial risk factor for exacerbation in or after a subsequent pregnancy. Further research is needed to identify factors related to exacerbation, so that physicians may provide appropriate recommendations to women regarding clinical issues involving OCD and reproductive cycle events.

Personality and cognitive decline in the Baltimore Epidemiologic Catchment Area follow-up study.

OBJECTIVE: To determine the association between personality domains and 11-year cognitive decline in a sample from a population-based study. METHOD: Data from Waves 3 (1993-1996) and 4 (2003-2004) of the Baltimore cohort of the Epidemiologic Catchment Area (ECA) study were used for analyses. The sample included 561 adults (mean age ± SD: 45.2 ± 10.78 years) who completed the NEO Personality Inventory-Revised prior to Wave 4. Participants also completed the Mini-Mental State Examination (MMSE) and immediate and delayed word recall tests at Wave 3, and at Wave 4, 10.9 ± 0.6 years later. RESULTS: In models adjusted for baseline cognitive performance, demographic characteristics, medical conditions, depressive symptoms, and psychotropic medication use, each 10-point increase in Neuroticism T-scores was associated with a 0.15-point decrease in MMSE scores (B = -0.15, 95% confidence interval [CI]: -0.30, -0.01), whereas each 10-point increase in Conscientiousness T-scores was associated with a 0.18-point increase on the MMSE (B = 0.18, 95% CI: 0.04, 0.32) and a 0.21-point increase in immediate recall (B = 0.21, 95% CI: 0.003, 0.41) between baseline and follow-up. CONCLUSION: Findings suggest that greater Neuroticism is associated with decline, and greater Conscientiousness is associated with improvement in performance on measures of general cognitive function and memory in adults. Further studies are needed to determine the extent to which personality traits in midlife are associated with clinically significant cognitive outcomes in older adults, such as mild cognitive impairment and dementia, and to identify potential mediators of the association between personality and cognitive trajectories.

Cognitive functioning in compulsive hoarding.

The aim of this study is to determine whether neurocognitive performance distinguishes individuals with compulsive hoarding (CH) from those with obsessive-compulsive disorder (OCD). Compared to control subjects, OCD patients and CHs scored significantly worse on the Serial Reaction Time Task suggesting disturbed implicit memory in both patient groups. On the Iowa Gambling Task, an overall learning progression difference over time was found between the CHs, OCD group, and control subjects, suggesting differences in decision-making between the groups. The groups did not differ in performance on the Stop Signal Reaction Time Task (motor inhibition). This study found evidence for impaired implicit memory in CHs, but also in OCD patients, albeit less severe. There was evidence that OCD patients learned more slowly on a decision-making task than CHs and control subjects. This latter finding provides some evidence to suggest that CH and OCD have, at least on this one measure, differing cognitive substrates.

Association between a serotonin transporter promoter polymorphism (5HTTLPR) and personality disorder traits in a community sample.

BACKGROUND: The serotonin transporter (SERT) polymorphism (5HTTLPR) has been reported to be associated with several psychiatric conditions. Specific personality disorders could be intermediate factors in the known relationship between 5HTTLPR and psychiatric disorders. This is the first study to test the association between this polymorphism and dimensions of all DSM-IV personality disorders in a community sample. METHODS: 374 white participants were assessed by clinical psychologists using the International Personality Disorder Examination (IPDE). Associations between dimensions of each DSM-IV personality disorder and the long (l) and short (s) alleles of the 5HTTLPR were evaluated using non-parametric tests and regression models. RESULTS: The s allele of the 5HTTLPR polymorphism was significantly associated with higher avoidant personality trait scores in the whole sample. Males with the s allele had a significantly lower likelihood of higher obsessive-compulsive personality disorder (OCPD) trait scores, whereas females with the s allele were likely to have higher OCPD personality trait scores. CONCLUSION: This paper provides preliminary data on the relationship between personality disorders and the 5HTTLPR polymorphism. The relationship of the s allele and avoidant PD is consistent with findings of a nonspecific relationship of this polymorphism to anxiety and depressive disorders. Concerning the unusual sexual dimorphic result with OCPD, several hypotheses are presented. These findings need further replication, including a more detailed study of additional variants in SERT.

Separation anxiety disorder in OCD.

BACKGROUND: A history of separation anxiety disorder (SAD) is frequently reported by patients with obsessive-compulsive disorder (OCD). The purpose of this study was to determine if there are clinical differences between OCD-affected individuals with, versus without, a history of SAD. METHODS: Using data collected during the OCD Collaborative Genetic Study, we studied 470 adult OCD participants; 80 had a history of SAD, whereas 390 did not. These two groups were compared as to onset and severity of OCD, lifetime prevalence of Axis I disorders, and number of personality disorder traits. RESULTS: OCD participants with a history of SAD were significantly younger than the non-SAD group (mean, 34.2 versus 42.2 years; P<.001). They had an earlier age of onset of OCD symptoms (mean, 8.0 versus 10.5 years; P<.003) and more severe OCD, as measured by the Yale-Brown Obsessive Compulsive Scale (mean, 27.5 versus 25.0; P<.005). In addition, those with a history of SAD had a significantly greater lifetime prevalence of agoraphobia (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.4-4.6, P<.003), panic disorder (OR = 1.84, CI = 1.03-3.3 P<.04), social phobia (OR = 1.69, CI 1.01-2.8, P<.048), after adjusting for age at interview, age at onset of OCD, and OCD severity in logistic regression models. There was a strong relationship between the number of dependent personality disorder traits and SAD (adjusted OR = 1.42, CI = 1.2-1.6, P<.001). CONCLUSIONS: A history of SAD is associated with anxiety disorders and dependent personality disorder traits in individuals with OCD.

Genetics of obsessive-compulsive disorder.

Obsessive-compulsive disorder is a common debilitating condition affecting individuals from childhood through adult life. There is good evidence of genetic contribution to its etiology, but environmental risk factors also are likely to be involved. The condition probably has a complex pattern of inheritance. Molecular studies have identified several potentially relevant genes, but much additional research is needed to establish definitive causes of the condition.

Recent advances in the genetics of obsessive-compulsive disorder.

This article reviews recent developments in understanding the genetic etiology of obsessive-compulsive disorder (OCD). Family studies provide further support for the familial aggregation of OCD. Genome-wide linkage studies indicate that specific chromosomal regions are linked to OCD. Moreover, results from recent molecular genetic studies suggest that several candidate genes are associated with OCD. However, specific genes causing OCD have not been conclusively identified, and the molecular pathogenesis of the disorder has not been elucidated. The search for genes is complicated by the clinical and etiologic heterogeneity of OCD, as well as the possibility of gene-gene and gene-environment interactions. Despite this complexity, further refinement of the phenotype and developments in molecular and statistical genetics hold promise for further deepening our genetic understanding of OCD in the future.

Personality disorder traits as predictors of subsequent first-onset panic disorder or agoraphobia.

Determining how personality disorder traits and panic disorder and/or agoraphobia relate longitudinally is an important step in developing a comprehensive understanding of the etiology of panic/agoraphobia. In 1981, a probabilistic sample of adult (> or =18 years old) residents of east Baltimore were assessed for Axis I symptoms and disorders using the Diagnostic Interview Schedule (DIS); psychiatrists reevaluated a subsample of these participants and made Axis I diagnoses, as well as ratings of individual Diagnostic and Statistical Manual of Mental Disorders, Third Edition personality disorder traits. Of the participants psychiatrists examined in 1981, 432 were assessed again in 1993 to 1996 using the DIS. Excluding participants who had baseline panic attacks or panic-like spells from the risk groups, baseline timidity (avoidant, dependent, and related traits) predicted first-onset DIS panic disorder or agoraphobia over the follow-up period. These results suggest that avoidant and dependent personality traits are predisposing factors, or at least markers of risk, for panic disorder and agoraphobia-not simply epiphenomena.

Sex-specific clinical correlates of hoarding in obsessive-compulsive disorder.

Little is known about whether the clinical correlates of hoarding behavior are different in men and women with obsessive-compulsive disorder (OCD). In the current study, we evaluated the association of hoarding with categories of obsessions and compulsions, psychiatric disorders, personality dimensions, and other clinical characteristics separately in 151 men and 358 women with OCD who were examined during the OCD Collaborative Genetics Study. We found that, among men but not women, hoarding was associated with aggressive, sexual, and religious obsessions and checking compulsions. In men, hoarding was associated with generalized anxiety disorder and tics whereas, among women, hoarding was associated with social phobia, post-traumatic stress disorder, body dysmorphic disorder, nail biting, and skin picking. In women but not men, hoarding was associated with schizotypal and dependent personality disorder dimensions, and with low conscientiousness. These findings indicate that specific clinical correlates of hoarding in OCD are different in men and women and may reflect sex-specific differences in the course, expression, and/or etiology of hoarding behavior in OCD.

Further development of YBOCS dimensions in the OCD Collaborative Genetics study: symptoms vs. categories.

Despite progress in identifying homogeneous subphenotypes of obsessive-compulsive disorder (OCD) through factor analysis of the Yale Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC), prior solutions have been limited by a reliance on presupposed symptom categories rather than discrete symptoms. Furthermore, there have been few attempts to evaluate the familiality of OCD symptom dimensions. The purpose of this study was to extend prior work by this collaborative group in category-based dimensions by conducting the first-ever exploratory dichotomous factor analysis using individual OCD symptoms, comparing these results to a refined category-level solution, and testing the familiality of derived factors. Participants were 485 adults in the six-site OCD Collaborative Genetics Study, diagnosed with lifetime OCD using semi-structured interviews. YBOCS-SC data were factor analyzed at both the individual item and symptom category levels. Factor score intraclass correlations were calculated using a subsample of 145 independent affected sib pairs. The item- and category-level factor analyses yielded nearly identical 5-factor solutions. While significant sib-sib associations were found for four of the five factors, Hoarding and Taboo Thoughts were the most robustly familial (r ICC>or=0.2). This report presents considerable converging evidence for a five-factor structural model of OCD symptoms, including separate factor analyses employing individual symptoms and symptom categories, as well as sibling concordance. The results support investigation of this multidimensional model in OCD genetic linkage studies.

Prevalence and correlates of hoarding behavior in a community-based sample.

Little is known about the prevalence and correlates of hoarding behavior in the community. We estimated the prevalence and evaluated correlates of hoarding in 742 participants in the Hopkins Epidemiology of Personality Disorder Study. The prevalence of hoarding was nearly 4% (5.3%, weighted) and was greater in older than younger age groups, greater in men than women, and inversely related to household income. Hoarding was associated with alcohol dependence; paranoid, schizotypal, avoidant, and obsessive-compulsive personality disorder traits; insecurity from home break-ins and excessive physical discipline before 16 years of age; and parental psychopathology. These findings suggest that hoarding may be relatively prevalent and that alcohol dependence, personality disorder traits, and specific childhood adversities are associated with hoarding in the community.

Demographic and clinical characteristics associated with treatment status in family members with obsessive-compulsive disorder.

This study investigated the demographic and clinical factors that influence treatment status in family members with obsessive compulsive disorder (OCD). Six hundred and two subjects from the OCD Collaborative Genetics Study were interviewed using the Structured Clinical Interview for DSM-IV (SCID) to diagnose Axis I disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for assessment of OCD symptoms. The demographic and clinical data were compared between subjects who had received treatment and those who had not. A precipitous onset of symptoms, severe illness, multiple obsessions and compulsions, and co-morbid affective disorders were all positively associated with receiving treatment. Older age and the presence of obsessive compulsive personality disorder (OCPD) or OCPD traits were negatively associated with treatment. Gender and age at onset of symptoms did not predict treatment history. The mean duration from onset of symptoms to receiving treatment was 13.8+/-SD 11.9 years, but there was a direct relationship between current age and time to treatment, with younger subjects receiving treatment sooner. Clinical factors are predominant in predicting treatment status in family members with OCD. Although the mean duration from onset of symptoms to treatment was long, younger family members appear to receive treatment sooner.

Hoarding in obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study.

Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study. We found that, compared to non-hoarding individuals, hoarders were more likely to have symmetry obsessions and repeating, counting, and ordering compulsions; poorer insight; more severe illness; difficulty initiating or completing tasks; and indecision. Hoarders had a greater prevalence of social phobia and generalized anxiety disorder. Hoarders also had a greater prevalence of obsessive-compulsive and dependent personality disorders. Five personality traits were independently associated with hoarding: miserliness, preoccupation with details, difficulty making decisions, odd behavior or appearance, and magical thinking. Hoarding and indecision were more prevalent in the relatives of hoarding than of non-hoarding probands. Hoarding in relatives was associated with indecision in probands, independently of proband hoarding status. The findings suggest that hoarding behavior may help differentiate a distinct clinical subgroup of people with OCD and may aggregate in some OCD families. Indecision may be a risk factor for hoarding in these families.

The OCD collaborative genetics study: methods and sample description.

Results from twin and family studies suggest that obsessive-compulsive disorder (OCD) may be transmitted in families but, to date, genes for the disorder have not been identified. The OCD Collaborative Genetics Study (OCGS) is a six-site collaborative genetic linkage study of OCD. Specimens and blinded clinical data will be made available through the National Institute of Mental Health (NIMH) cell repository. In this initial report, we describe the methods of the study and present clinical characteristics of affected individuals for researchers interested in this valuable resource for genetic studies of OCD. The project clinically evaluated and collected blood specimens from 238 families containing 299 OCD-affected sibling pairs and their parents, and additional affected relative pairs, for a genome-wide linkage study. Of the 999 individuals interviewed to date, 624 were diagnosed with "definite" OCD. The mean age of subjects was 36 years (range 7-95). The majority of affected individuals (66%) were female. The mean age at onset of obsessive-compulsive symptoms was 9.5 years. Specific mood disorders, anxiety disorders, eating disorders, and skin picking were more prevalent in female cases, whereas tics, Tourette disorder, and alcohol dependence were more prevalent in male cases. Compared to "definite" cases of OCD, "probable" cases (n = 82) had, on average, later age at onset of obsessive-compulsive symptoms, lower severity score, and fewer numbers of different categories of obsessions and compulsions, and they were less likely to have received treatment for their symptoms.

Anxiety and depressive disorders and the five-factor model of personality: a higher- and lower-order personality trait investigation in a community sample.

We describe in detail normal personality traits in persons with psychiatrist-ascertained anxiety and depressive disorders in a general population sample. We investigated Revised NEO Personality Inventory traits in 731 community subjects examined by psychiatrists with the Schedules for Clinical Assessment in Neuropsychiatry. All of the lifetime disorders of interest (simple phobia, social phobia, agoraphobia, panic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder, major depressive disorder (MDD), and dysthymia) were associated with high neuroticism. Social phobia, agoraphobia, and dysthymia were associated with low extraversion, and OCD was associated with high openness to experience. In addition, lower-order facets of extraversion (E), openness (O), agreeableness (A), and conscientiousness (C) were associated with certain disorders (specifically, low assertiveness (E) and high openness to feelings (O) with MDD, low trust (A) with social phobia and agoraphobia, low self-discipline (C) with several of the disorders, and low competence and achievement striving (C) with social phobia). Neuroticism in particular was related to acuity of disorder. Longitudinal study is necessary to differentiate state versus pathoplastic effects.