Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics ...Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 × 10
; odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11), rs1030757 (P=1.1 × 10
; OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 × 10
; OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case-control status in the other by explaining 0.9% (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Genetics of obsessive-compulsive disorder Purty, Abhishek; Nestadt, Gerald; Samuels, Jack ...
Indian journal of psychiatry,
01/2019, Volume:
61, Issue:
7
Journal Article
Peer reviewed
Open access
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Like most human behaviors, saving and collecting possessions can range from totally normal and adaptive to excessive or pathological. Hoarding, or compulsive hoarding, are some of the more commonly ...used terms to refer to this excessive form of collectionism. Hoarding is highly prevalent and, when severe, it is associated with substantial functional disability and represents a great burden for the sufferers, their families, and society in general. It is generally considered difficult to treat. Hoarding can occur in the context of a variety of neurological and psychiatric conditions. Although it has frequently been considered a symptom (or symptom dimension) of obsessive–compulsive disorder, and is listed as one of the diagnostic criteria for obsessive–compulsive personality disorder, its diagnostic boundaries are still a matter of debate. Recent data suggest that compulsive hoarding can also be a standalone problem. Growing evidence from epidemiological, phenomenological, neurobiological, and treatment studies suggests that compulsive hoarding may be best classified as a discrete disorder with its own diagnostic criteria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
6.
Genetics of obsessive-compulsive disorder Nestadt, Gerald; Grados, Marco; Samuels, Jack F
The Psychiatric clinics of North America,
03/2010, Volume:
33, Issue:
1
Journal Article
Peer reviewed
Open access
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.
To determine the association between personality domains and 11-year cognitive decline in a sample from a population-based study.
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.
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.
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.
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.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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
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.
•In a community sample, we found an association of the SERT S allele with an increased risk for panic disorder, and a decreased risk for OCD.•SERT S allele was associated with increased risk for PD, a decreased risk for OCD, and increased risk for comorbidity between MDD, PD, Agoraphobia.•The SERT S allele was not associated with an increased risk for psychopathology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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