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
). 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
). These data support a contribution of rare coding variants to OCD genetic risk.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Acute lung injury (ALI), including its more severe subcategory, acute respiratory distress syndrome (ARDS), is a critical illness associated with considerable morbidity and mortality. Our objective ...was to summarize data on the prevalence of depressive, posttraumatic stress disorder (PTSD), and other anxiety syndromes amongst survivors of ALI/ARDS, potential risk factors for these syndromes, and their relationships to quality of life.
We conducted a systematic literature review using Medline, EMBASE, Cochrane Library, CINAHL, and PsycINFO. Eligible studies reported data on psychiatric morbidity at least once after intensive care treatment of ALI/ARDS.
Ten observational studies met inclusion criteria (total n = 331). Using questionnaires, the point prevalence of "clinically significant" symptoms of depression ranged from 17% to 43% (4 studies); PTSD, 21% to 35% (4 studies); and nonspecific anxiety, 23% to 48% (3 studies). Studies varied in terms of instruments used, thresholds for clinical significance, baseline psychiatric history exclusions, and timing of assessments (range = 1 month to 8 years). Psychiatrist-diagnosed PTSD prevalence at hospital discharge, 5 years, and 8 years were 44%, 25%, and 24%, respectively. Three studies prospectively assessed risk factors for post-ALI/ARDS PTSD and depressive symptoms; significant predictors included longer durations of mechanical ventilation, intensive care unit stay, and sedation. All four studies that examined relationships between psychiatric symptoms and quality of life found significant negative associations.
The prevalence of psychiatric morbidity in patients surviving ARDS seems high. Future research should incorporate more in-depth diagnostic and risk factor assessments for prevention and monitoring purposes.
Knowledge of the prevalence and correlates of personality disorders in the community is important for identifying treatment needs and for provision of psychiatric services.
To estimate the prevalence ...of personality disorders in a community sample and to identify demographic subgroups with especially high prevalence.
Clinical psychologists used the International Personality Disorder Examination to assess DSM-IV and ICD-10 personality disorders in a sample of 742 subjects, ages 34-94 years, residing in Baltimore, Maryland. Logistic regression was used to evaluate the association between demographic characteristics and DSM-IV personality disorder clusters.
The estimated overall prevalence of DSM-IV personality disorders was 9%. Cluster A disorders were most prevalent in men who had never married. Cluster B disorders were most prevalent in young men without a high school degree, and cluster C disorders in high school graduates who had never married.
Approximately 9% of this community sample has a DSM-IV personality disorder. Personality disorders are over-represented in certain demographic subgroups of the community.
Genetic association studies of SLC6A4 (SERT) and obsessive-compulsive disorder (OCD) have been equivocal. We genotyped 1241 individuals in 278 pedigrees from the OCD Collaborative Genetics Study for ...13 single-nucleotide polymorphisms, for the linked polymorphic region (LPR) indel with molecular haplotypes at rs25531, for VNTR polymorphisms in introns 2 and 7 and for a 381-bp deletion 3' to the LPR. We analyzed using the Family-Based Association Test (FBAT) under additive, dominant, recessive and genotypic models, using both OCD and sex-stratified OCD as phenotypes. Two-point FBAT analysis detected association between Int2 (P = 0.0089) and Int7 (P = 0.0187) (genotypic model). Sex-stratified two-point analysis showed strong association in females with Int2 (P<0.0002), significant after correction for linkage disequilibrium, and multiple marker and model testing (P(Adj) = 0.0069). The SLC6A4 gene is composed of two haplotype blocks (our data and the HapMap); FBAT whole-marker analysis conducted using this structure was not significant. Several noteworthy nonsignificant results have emerged. Unlike Hu et al., we found no evidence for overtransmission of the LPR L(A) allele (genotype relative risk = 1.11, 95% confidence interval: 0.77-1.60); however, rare individual haplotypes containing L(A) with P<0.05 were observed. Similarly, three individuals (two with OCD/OCPD) carried the rare I425V SLC6A4 variant, but none of them passed it on to their six OCD-affected offspring, suggesting that it is unlikely to be solely responsible for the 'OCD plus syndrome', as reported by Ozaki et al. In conclusion, we found evidence of genetic association at the SLC6A4 locus with OCD. A noteworthy lack of association at the LPR, LPR-rs25531 and rare 425V variants suggests that hypotheses about OCD risk need revision to accommodate these new findings, including a possible gender effect.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the ...underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10−7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Evidence from twin and family studies supports a genetic etiology for obsessive-compulsive disorder (OCD). The purpose of this study was to test whether a major gene is implicated in a proportion of ...families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a major gene. A Mendelian-dominant model, with significant sex effects and with residual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogeneity with respect to familial aggregation. Segregation analyses of 86 families with a female proband and of the 67 families with a male proband suggested that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study investigates the relationship of specific anxiety and affective disorders to obsessive-compulsive disorder (OCD) in a blind, controlled family study.
Eighty case and 73 control probands, ...as well as 343 case and 300 control first-degree relatives of these probands, participated in the study. Subjects were examined by psychologists or psychiatrists using the Schedule for Affective Disorder and Schizophrenia-Lifetime Anxiety version (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials, and final diagnoses were made according to DSM-IV criteria, by consensus procedure.
Except for bipolar disorder, all anxiety and affective disorders investigated were more frequent in case than control probands. Substance dependence disorders were not more frequent. Generalized anxiety disorder (GAD), panic disorder, agoraphobia, separation anxiety disorder (SAD) and recurrent major depression were more common in case than control relatives. These disorders occurred more frequently if the relative was diagnosed with OCD. Only GAD and agoraphobia were more frequent in case relatives independent of OCD.
GAD and agoraphobia share a common familial aetiology with OCD. The other anxiety and affective disorders, when comorbid with OCD, may emerge as a consequence of the OCD or as a more complex syndrome.
Little is known about personality disorders and normal personality dimensions in relatives of patients with obsessive-compulsive disorder (OCD).
To determine whether specific personality ...characteristics are part of a familial spectrum of OCD.
Clinicians evaluated personality disorders in 72 OCD case and 72 control probands and 198 case and 207 control first-degree relatives. The selfcompleted Revised NEO Personality Inventory was used for assessment of normal personality dimensions. The prevalence of personality disorders and scores on normal personality dimensions were compared between case and control probands and between case and control relatives.
Case probands and case relatives had a high prevalence of obsessive-compulsive personality disorder (OCPD) and high neuroticism scores. Neuroticism was associated with OCPD in case but not control relatives.
Neuroticism and OCPD may share a common familial aetiology with OCD.
Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and ...co-morbid conditions to identify subtypes.
Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD). The relationship of the derived classes to specific clinical characteristics was investigated.
Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive-compulsive personality disorder (OCPD) features, high scores on the 'taboo' factor of OCD symptoms, and low conscientiousness.
OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors.
The Burden of Mental Disorders Eaton, William W.; Martins, Silvia S.; Nestadt, Gerald ...
Epidemiologic reviews,
11/2008, Volume:
30, Issue:
1
Journal Article
Peer reviewed
Open access
In the last decade, there has been an increase in interest in the burden of chronic and disabling health conditions that are not necessarily fatal, such as the mental disorders. This review ...systematically summarizes data on the burden associated with 11 major mental disorders of adults. The measures of burden include estimates of prevalence, mortality associated with the disorders, disabilities and impairments related to the disorders, and costs. This review expands the range of mental disorders considered in a report on the global burden of disease, updates the literature, presents information on the range and depth of sources of information on burden, and adds estimates of costs. The purpose is to provide an accessible guide to the burden of mental disorders, especially for researchers and policy makers who may not be familiar with this subfield of epidemiology.
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