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Are stressful life events causally related to the severity of obsessive-compulsive symptoms? A monozygotic twin difference study.

ABSTRACT: Traumatic or stressful life events have long been hypothesized to play a role in causing or precipitating obsessive-compulsive symptoms but the impact of these environmental factors has rarely been investigated using genetically informative designs. We tested whether a wide range of retrospectively-reported stressful life events (SLEs) influence the lifetime presence and severity of obsessive-compulsive symptoms (OCS) in a large Swedish population-based cohort of 22,084 twins. Multiple regression models examined whether differences in SLEs within twin pairs were significantly associated with differences in OCS. In the entire sample (i.e., both monozygotic [MZ] and dizygotic twin pairs), two SLEs factors, "abuse and family disruption" and "sexual abuse", were significantly associated with the severity of OCS even after controlling for depressive symptoms. Other SLEs factors were either not associated with OCS ("loss", "non-sexual assault") or were no longer associated with OCS after controlling for depression ("illness/injury"). Within MZ pair analyses, which effectively control for genetic and shared environmental effects, showed that only the "abuse and family disruption" factor remained independently related to within-pair differences in OCS severity, even after controlling for depressive symptoms. Despite being statistically significant, the magnitude of the associations was small; "abuse and family disruption" explained approximately 3% of the variance in OCS severity. We conclude that OCS are selectively associated with certain types of stressful life events. In particular, a history of interpersonal abuse, neglect and family disruption may make a modest but significant contribution to the severity of OCS. Further replication in longitudinal cohorts is essential before causality can be firmly established.

SUBMITTER: Vidal-Ribas P

PROVIDER: S-EPMC4331096 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To investigate environmental factors that protect against or exacerbate obsessive-compulsive (OC) symptoms, we selected 25 monozygotic (MZ) twin pairs discordant, 17 MZ twin pairs concordant high and 34 MZ pairs concordant low on OC symptoms from a large longitudinal Dutch sample of adult twin pairs and their family members, applying stringent criteria for OC symptomatology. Data were collected on psychopathology, family structure, health, lifestyle, birth complications and life events. Unique environmental factors were studied using within-discordant MZ pair comparisons, whereas between-concordant MZ pair comparisons were used to study environmental factors that are shared by the twins of an MZ pair. The high-scoring MZ twins of the discordant group reported more life events (especially sexual abuse) than their low-scoring twin-siblings. The between-pair comparisons showed lower birth weight in the discordant MZ pairs than in the concordant MZ pairs. Further, the concordant high MZ pairs as well as their spouses had a lower educational level than the two other groups. On scale scores of anxious-depression, neuroticism, and somatic complaints, concordant high MZ pairs showed highest scores, and the discordant MZ pairs scored intermediate, except for neuroticism, on which the high-scoring twins of discordant MZ pairs were equal to the concordant high pairs. Discordance on psychological scale scores between the concordant MZ pairs was evident from 1991 onward, and within the discordant MZ pairs from 1997 onward, confirming previous reports of an association of early-onset OC symptoms with higher genetic load. Parent scores of OC symptoms and anxious-depression suggested intermediate genetic load in the discordant MZ group. In conclusion, this study reports on both unique and shared environmental factors associated with OC symptomatology. Whether these factors operate in addition to or in interaction with genetic disposition is to be elucidated in future studies.

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.

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Are stressful life events causally related to the severity of obsessive-compulsive symptoms? A monozygotic twin difference study.

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