Experts have proposed removing obsessive-compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity ...and familiality data to inform these issues.
Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives).
Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive-compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously.
On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.
We assess the annual economic burden of anxiety disorders in the United States from a societal perspective.
Using data from the National Comorbidity Study, we applied multivariate regression ...techniques to calculate the costs associated with anxiety disorders, after adjusting for demographic characteristics and the presence of comorbid psychiatric conditions. Based on additional data, in part from a large managed care organization, we estimated a human capital model of the societal cost of anxiety disorders.
We estimated the annual cost of anxiety disorders to be approximately $42.3 billion in 1990 in the United States, or $1542 per sufferer. This comprises $23.0 billion (or 54% of the total cost) in nonpsychiatric medical treatment costs, S13.3 billion (31%) in psychiatric treatment costs, $4.1 billion (10%) in indirect workplace costs, $1.2 billion (3%) in mortality costs, and $0.8 billion (2%) in prescription pharmaceutical costs. Of the $256 in workplace costs per anxious worker, 88% is attributable to lost productivity while at work as opposed to absenteeism. Posttraumatic stress disorder and panic disorder are the anxiety disorders found to have the highest rates of service use. Other than simple phobia, all anxiety disorders analyzed are associated with impairment in workplace performance.
Anxiety disorders impose a substantial cost on society, much of which may be avoidable with more widespread awareness, recognition, and appropriate early intervention.
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
Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not ...been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed.
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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
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
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
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.
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