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Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene.

ABSTRACT: Neuroticism is a personality trait reflecting the tendency to experience negative affect. It is a major risk for psychopathology, especially depression and anxiety disorders. Childhood maltreatment is another major risk factor for psychopathology and may influence personality. Maltreatment may interact with genotype to predict developmental outcomes. Variation in three polymorphisms of the CRHR1 gene has been found to moderate the association of childhood maltreatment with depression, and we hypothesized that it would also be linked to neuroticism.Variation in three CRHR1 SNPs (rs110402, rs242924, rs7209436) was assessed in 339 maltreated and 275 demographically similar nonmaltreated children, who participated in a day camp research program. Maltreated children were further categorized based on the number of types of maltreatment they had experienced and the most severe form of maltreatment experienced. Genotype and maltreatment status were used to predict the Big Five personality traits, as assessed by camp counselors following a week of interaction with children.? CRHR1 genotype significantly moderated the association of maltreatment with neuroticism but none of the other traits. Having two copies of the TAT haplotype of CRHR1 was associated with higher levels of neuroticism among maltreated children relative to nonmaltreated children, with the exception of sexually abused children and children who had experienced 3 or 4 types of abuse. Effects sizes of these interactions ranged from ?2=.01 (p=.02) to ?2=.03 (p=.006).Variation in CRHR1 moderates the association of maltreatment with neuroticism. The effects of specific types of maltreatment on neuroticism are differentially moderated by CRHR1 genotype, as are the effects of experiencing more or fewer types of maltreatment.

SUBMITTER: DeYoung CG

PROVIDER: S-EPMC3134545 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene.

DeYoung Colin G CG Cicchetti Dante D Rogosch Fred A FA

Journal of child psychology and psychiatry, and allied disciplines 20110325 8

<h4>Background</h4>Neuroticism is a personality trait reflecting the tendency to experience negative affect. It is a major risk for psychopathology, especially depression and anxiety disorders. Childhood maltreatment is another major risk factor for psychopathology and may influence personality. Maltreatment may interact with genotype to predict developmental outcomes. Variation in three polymorphisms of the CRHR1 gene has been found to moderate the association of childhood maltreatment with dep ...[more]

PMID: 21438878

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Project description:Genetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression.To examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene.Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms.General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia.The primary participant population was 97.4% African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7% Caucasian) and socioeconomically (less impoverished).Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders.Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199).These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.

Project description:Corticotropin-releasing hormone (CRH) plays an important role in the pathophysiology of irritable bowel syndrome (IBS) and regulates the stress response through two CRH receptors (R1 and R2). Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436) and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients.A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs) of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220) were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-Rating Depression Scale.We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017) and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS), and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710) and two SNPs (rs2284217 and rs2284220) in strong linkage disequilibrium (D' > 0.90). We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion.Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH system are warranted.

Dataset Information

Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene.

Publications

Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene.

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