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Disrupted computations of social control in individuals with obsessive-compulsive and misophonia symptoms.

ABSTRACT: Misophonia is a disorder in which certain sounds produced by other people lead to intense negative reactions. It remains unknown how misophonia relates to other psychiatric conditions or impairments. To identify latent constructs underlying symptoms, we conducted a factor analysis consisting of items from questionnaires assessing symptoms of misophonia and other psychiatric conditions. One thousand forty-two participants completed the questionnaires and a social exchange task in which they either could ("controllable") or could not ("uncontrollable") influence future monetary offers from other people. Misophonia and obsessive-compulsive (OC) symptoms loaded onto the same factor. Compared with individuals with low Miso-OC factor scores, individuals with high scores reported higher perceived controllability of their social interactions during the uncontrollable condition and stronger aversion to social norm violations in the uncontrollable compared with the controllable condition. Together, these results suggest misophonia, and OC symptoms share a latent psychiatric dimension characterized by aberrant computations of social controllability.

SUBMITTER: Banker SM

PROVIDER: S-EPMC9253698 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Disrupted computations of social control in individuals with obsessive-compulsive and misophonia symptoms.

Banker Sarah M SM Na Soojung S Beltrán Jacqueline J Koenigsberg Harold W HW Foss-Feig Jennifer H JH Gu Xiaosi X Schiller Daniela D

iScience 20220616 7

Misophonia is a disorder in which certain sounds produced by other people lead to intense negative reactions. It remains unknown how misophonia relates to other psychiatric conditions or impairments. To identify latent constructs underlying symptoms, we conducted a factor analysis consisting of items from questionnaires assessing symptoms of misophonia and other psychiatric conditions. One thousand forty-two participants completed the questionnaires and a social exchange task in which they eithe ...[more]

PMID: 35800773

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Project description:While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed = 3.06 × 10-5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes = 28, Beta = 0.79, SE = 0.16, Pbon = 0.008). Expression of genes in this set is high at sites of insulin mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33-43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG = 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.

Project description:We investigated whether obsessive-compulsive (OC) symptoms from a population-based sample could be analyzed to detect genetic variants influencing obsessive-compulsive disorder (OCD). We performed a genome-wide association studies (GWAS) on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N = 8,267 with genome-wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case-control GWAS (r G = 0.61, p = .017) previously published by the Psychiatric Genomics Consortium (PGC-OCD). The obsession subscale and the total Padua score showed no significant genetic correlations (r G = -0.02 and r G = 0.42, respectively). A meta-analysis of the compulsive symptoms GWAS with the PGC-OCD revealed no genome-wide significant Single-Nucleotide Polymorphisms (SNPs combined N = 17,992, indicating that the power is still low for individual SNP effects). A gene-based association analysis, however, yielded two novel genes (WDR7 and ADCK1). The top 250 genes in the gene-based test also showed a significant increase in enrichment for psychiatric and brain-expressed genes. S-Predixcan testing showed that for genes expressed in hippocampus, amygdala, and caudate nucleus significance increased in the meta-analysis with compulsive symptoms compared to the original PGC-OCD GWAS. Thus, the inclusion of dimensional symptom data in genome-wide association on clinical case-control GWAS of OCD may be useful to find genes for OCD if the data are based on quantitative indices of compulsive behavior. SNP-level power increases were limited, but aggregate, gene-level analyses showed increased enrichment for brain-expressed genes related to psychiatric disorders, and increased association with gene expression in brain tissues with known emotional, reward processing, memory, and fear-formation functions.

Dataset Information

Disrupted computations of social control in individuals with obsessive-compulsive and misophonia symptoms.

Publications

Disrupted computations of social control in individuals with obsessive-compulsive and misophonia symptoms.

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