title: 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.
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. kranzler_h@mail.trc.upenn.edu
authors: Henry R
authors: HR
authors: Kranzler
authors: Richard
authors: R
authors: Feinn
authors: Elliot C
authors: EC
authors: Nelson
authors: Jonathan
authors: J
authors: Covault
authors: Raymond F
authors: RF
authors: Anton
authors: Lindsay
authors: L
authors: Farrer
authors: Joel
authors: J
authors: Gelernter
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D002648:Child; D002649:Child Abuse / Q000523:psychology; D003863:Depression / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013315:Stress, Psychological; D019966:Substance-Related Disorders / Q000235:genetics*; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1