Childhood maltreatment, the corticotropin-releasing hormone receptor gene and adult depression in the general population.
Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin-releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT-haplotype of the CRH-Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of the CRHR1 gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI-2). The CRHR1-SNPs were genotyped on the Affymetrix Genome-Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT-haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P < 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching "gene-wide" significance. Although we did not replicate the specific interaction of abuse and the TAT-haplotype of the CRHR1 gene we confirmed the relevance of an interplay between variants within the CRHR1 gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI-2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene-environment interaction findings. © 2010 Wiley-Liss, Inc.
Department of Psychiatry and Psychotherapy, University of Greifswald, Greifswald, Germany. grabeh@uni-greifswald.de
Hans Jörgen
HJ
Grabe
Christian
C
Schwahn
Katja
K
Appel
Jessie
J
Mahler
Andrea
A
Schulz
Carsten
C
Spitzer
Kristin
K
Fenske
Sven
S
Barnow
Michael
M
Lucht
Harald Jürgen
HJ
Freyberger
Ulrich
U
John
Alexander
A
Teumer
Henri
H
Wallaschofski
Matthias
M
Nauck
Henry
H
Völzke
D000328:Adult; D000368:Aged; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D003865:Major Depressive Disorder / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011581:Psychological Tests; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1