Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: effects on hypothalamic-pituitary-adrenal axis reactivity.
BACKGROUND
Variation in the corticotropin-releasing hormone receptor (CRHR1) gene has been shown to interact with early life stress to predict adult depression. This study was conducted to determine whether CRHR1 polymorphisms interact with childhood maltreatment to predict hypothalamic-pituitary-adrenal (HPA) axis reactivity, which has been linked to both depression and early life stress.


METHODS
One hundred twenty-nine White, non-Hispanic adults completed the Childhood Trauma Questionnaire and the dexamethasone/corticotropin-releasing hormone (DEX/CRH) test, and provided blood samples for genotyping of two CRHR1 polymorphisms.


RESULTS
Both rs110402 and rs242924 (which were in tight linkage disequilibrium, D' = .98) showed a significant interaction with maltreatment in the prediction of cortisol response to the DEX/CRH test (p < .05). For subjects with maltreatment, the GG genotype of each single nucleotide polymorphism was associated with elevated cortisol responses to the test.


CONCLUSIONS
Variation in the CRHR1 moderates the effect of childhood maltreatment on cortisol responses to the DEX/CRH test. Excessive HPA axis activation could represent a mechanism of interactions of risk genes with stress in the development of mood and anxiety disorders.
Tyrka
Audrey R
AR
Mood Disorders Research Program and Laboratory for Clinical Neuroscience, Butler Hospital, Providence, Rhode Island 02906, USA. Audrey_Tyrka@Brown.edu
Price
Lawrence H
LH
Gelernter
Joel
J
Schepker
Caroline
C
Anderson
George M
GM
Carpenter
Linda L
LL
D000293:Adolescent; D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003863:Depression / Q000209:etiology / Q000235:genetics; D003907:Dexamethasone; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013315:Stress, Psychological / Q000209:etiology / Q000235:genetics*; D011795:Surveys and Questionnaires; D055815:Young Adult; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone