Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms.


METHODS
General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia.


METHODS
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).


METHODS
Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders.


RESULTS
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).


CONCLUSIONS
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.
Bradley
Rebekah G
RG
Atlanta VA Medical Center, Georgia, USA.
Binder
Elisabeth B
EB
Epstein
Michael P
MP
Tang
Yilang
Y
Nair
Hemu P
HP
Liu
Wei
W
Gillespie
Charles F
CF
Berg
Tiina
T
Evces
Mark
M
Newport
D Jeffrey
DJ
Stowe
Zachary N
ZN
Heim
Christine M
CM
Nemeroff
Charles B
CB
Schwartz
Ann
A
Cubells
Joseph F
JF
Ressler
Kerry J
KJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D044383:Black People / Q000235:genetics / Q000523:psychology; D002648:Child; D002649:Child Abuse / Q000175:diagnosis / Q000523:psychology*; D002885:Chromosomes, Human, Pair 16; D003431:Cross-Cultural Comparison; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012307:Risk Factors; D012931:Social Environment; D012959:Socioeconomic Factors; D044465:White People / Q000235:genetics / Q000523:psychology; D001741:Black or African American; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1