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A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African-American women.

ABSTRACT: Adverse childhood experiences (ACEs) increase the risk for adult depression and substance dependence, possibly mediated by the corticotropin-releasing hormone type 1 receptor (CRHR1). In some studies, a three-SNP "T-A-T" haplotype in CRHR1, which encodes CRHR1, exerted a protective moderating effect on risk of depression in adults with ACEs. Other studies have shown a main or moderating effect of SNPs in CRHR1 on alcohol consumption. We tested the moderating effects of the three-SNP haplotype on lifetime risk of a major depressive episode (MDE) and alcohol dependence (AD) in 1,211 European-Americans (EAs) and 1,869 African-Americans (AAs), most of whom had a lifetime substance use disorder. There were no significant main or interaction effects of the TAT haplotype on AD. There was a significant interaction of ACE by TAT on risk of depression only in AA women (P = 0.005); each copy of the TAT haplotype reduced the odds of MDE by almost 40% (OR = 0.63). In AA women without an ACE and two TAT haplotypes, the risk of MDE was increased (OR = 1.51 for each copy). Our findings in relation to the TAT haplotype of CRHR1 extend those obtained in other populations to a largely substance-dependent one. The complex structure of CRHR1 may help to explain why some variants in the gene moderate the effects of an ACE only on depression risk while others moderate the effect of an ACE only on AD risk.

SUBMITTER: Kranzler HR

PROVIDER: S-EPMC3227028 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African-American women.

Kranzler Henry R HR Feinn Richard R Nelson Elliot C EC Covault Jonathan J Anton Raymond F RF Farrer Lindsay L Gelernter Joel J

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20111013 8

Adverse childhood experiences (ACEs) increase the risk for adult depression and substance dependence, possibly mediated by the corticotropin-releasing hormone type 1 receptor (CRHR1). In some studies, a three-SNP "T-A-T" haplotype in CRHR1, which encodes CRHR1, exerted a protective moderating effect on risk of depression in adults with ACEs. Other studies have shown a main or moderating effect of SNPs in CRHR1 on alcohol consumption. We tested the moderating effects of the three-SNP haplotype on ...[more]

PMID: 21998007

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Project description:Exposure to social stress is a well-established risk factor for the development and recurrence of depression. Reduced neural responsiveness to monetary reward has been associated with greater symptoms following stress exposure. However, it remains unclear whether reduced reward responsiveness serves as a mediator or moderator of the effects of stress on internalizing symptoms or whether similar patterns emerge with responses to social reward. We addressed this issue by measuring lifetime stress exposure and event-related potentials (ERPs) to social reward in 231 emerging adults (M = 18.16, SD = 0.41 years old). Participants completed the Stress and Adversity Inventory (STRAIN) to assess severity of lifetime stressors and self-report measures of current internalizing symptoms. In addition, participants completed the Island Getaway task in which the reward positivity (RewP) ERP was recorded in response to social acceptance, adjusting for responses to rejection (RewP residual). In this task, participants vote to accept or reject peers and receive reward/acceptance and rejection feedback. Stressors were divided into social and non-social stress severity scores. Analyses were conducted to test social reward responsiveness as a mediator or moderator of the effects of social and non-social stress on internalizing symptoms. Both social and non-social stress exposure over the life course predicted symptoms of depression (ps < 0.001) and social anxiety (ps < 0.002). The effect of social stress on depression was moderated by the residual RewP to social reward, adjusting for responses to social rejection (p =0.024), such that greater lifetime social stress exposure and a relatively blunted RewP to social reward were associated with greater depressive symptoms. Social reward responsiveness did not mediate effects of stress on internalizing symptoms. Reduced processing of social reward may be a vulnerability for depression that increases risk for symptoms following exposure to social stress. Blunted social reward responsiveness appears to be a relatively unique vulnerability for depression, rather than social anxiety. Results support the utility of ERP measures in measuring individual differences in social reward processing that can be applied to better understand neural processes involved in the development of depression, and highlight the importance of considering specific dimensions of stressful life experiences.

Dataset Information

A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African-American women.

Publications

A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African-American women.

Similar Datasets

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