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Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene.

Heim C, Bradley B, Mletzko TC, Deveau TC, Musselman DL, Nemeroff CB, Ressler KJ, Binder EB - Front Behav Neurosci (2009)

Bottom Line: In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men.In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure.This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine Atlanta, GA, USA.

ABSTRACT
Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

No MeSH data available.


Related in: MedlinePlus

Interaction of CRHR1 rs110402 genotype and childhood abuse exposure on current depressive symptoms in men (N = 424) and women (N = 635). Graph depicts mean (SEM) total BDI scores in subjects grouped according to rs110402 allele status (GG, AG, AA) and exposure to none-mild versus moderate-severe childhood abuse. (A) In men, there was a significant main effect of childhood abuse exposure (F1, 423 = 8.20, p = 0.004) and a significant interaction effect of rs110402 by childhood abuse exposure (F2,423 = 3.50, p = 0.031) on BDI scores. (B) In women, there was a significant main effect of childhood abuse exposure on BDI score (F1,634 = 25.0, p < 0.0001), but no significant gene-environment interaction of rs110402 and childhood abuse exposure on BDI scores. The genotype distribution is given in the figure legend, with the first number representing the N in the non-mild abuse group and the second number the N in the moderate to severe abuse exposure group.
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Figure 1: Interaction of CRHR1 rs110402 genotype and childhood abuse exposure on current depressive symptoms in men (N = 424) and women (N = 635). Graph depicts mean (SEM) total BDI scores in subjects grouped according to rs110402 allele status (GG, AG, AA) and exposure to none-mild versus moderate-severe childhood abuse. (A) In men, there was a significant main effect of childhood abuse exposure (F1, 423 = 8.20, p = 0.004) and a significant interaction effect of rs110402 by childhood abuse exposure (F2,423 = 3.50, p = 0.031) on BDI scores. (B) In women, there was a significant main effect of childhood abuse exposure on BDI score (F1,634 = 25.0, p < 0.0001), but no significant gene-environment interaction of rs110402 and childhood abuse exposure on BDI scores. The genotype distribution is given in the figure legend, with the first number representing the N in the non-mild abuse group and the second number the N in the moderate to severe abuse exposure group.

Mentions: We tested the interaction of rs110402 genotype and any childhood abuse on current depressive symptoms in female and male subjects, separately. Analyses were conducted in 424 male and 635 female subjects (Figure 1). In women (Figure 1A), childhood abuse exposure was a significant predictor (F1, 634 = 25.0, p < 0.0001), but there was neither a main effect of genotype nor an interaction effect of genotype by sex. In men (Figure 1B), however, there was a significant main effect of childhood abuse exposure (F1, 423 = 8.20, p = 0.004) as well as a significant interaction effect of childhood abuse exposure by rs110402 genotype (F2,423 = 3.50, p = 0.031), whereas there was no main effect of the genotype. Specifically, men homozygous for the A allele were most protected from developing depression after childhood abuse.


Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene.

Heim C, Bradley B, Mletzko TC, Deveau TC, Musselman DL, Nemeroff CB, Ressler KJ, Binder EB - Front Behav Neurosci (2009)

Interaction of CRHR1 rs110402 genotype and childhood abuse exposure on current depressive symptoms in men (N = 424) and women (N = 635). Graph depicts mean (SEM) total BDI scores in subjects grouped according to rs110402 allele status (GG, AG, AA) and exposure to none-mild versus moderate-severe childhood abuse. (A) In men, there was a significant main effect of childhood abuse exposure (F1, 423 = 8.20, p = 0.004) and a significant interaction effect of rs110402 by childhood abuse exposure (F2,423 = 3.50, p = 0.031) on BDI scores. (B) In women, there was a significant main effect of childhood abuse exposure on BDI score (F1,634 = 25.0, p < 0.0001), but no significant gene-environment interaction of rs110402 and childhood abuse exposure on BDI scores. The genotype distribution is given in the figure legend, with the first number representing the N in the non-mild abuse group and the second number the N in the moderate to severe abuse exposure group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821197&req=5

Figure 1: Interaction of CRHR1 rs110402 genotype and childhood abuse exposure on current depressive symptoms in men (N = 424) and women (N = 635). Graph depicts mean (SEM) total BDI scores in subjects grouped according to rs110402 allele status (GG, AG, AA) and exposure to none-mild versus moderate-severe childhood abuse. (A) In men, there was a significant main effect of childhood abuse exposure (F1, 423 = 8.20, p = 0.004) and a significant interaction effect of rs110402 by childhood abuse exposure (F2,423 = 3.50, p = 0.031) on BDI scores. (B) In women, there was a significant main effect of childhood abuse exposure on BDI score (F1,634 = 25.0, p < 0.0001), but no significant gene-environment interaction of rs110402 and childhood abuse exposure on BDI scores. The genotype distribution is given in the figure legend, with the first number representing the N in the non-mild abuse group and the second number the N in the moderate to severe abuse exposure group.
Mentions: We tested the interaction of rs110402 genotype and any childhood abuse on current depressive symptoms in female and male subjects, separately. Analyses were conducted in 424 male and 635 female subjects (Figure 1). In women (Figure 1A), childhood abuse exposure was a significant predictor (F1, 634 = 25.0, p < 0.0001), but there was neither a main effect of genotype nor an interaction effect of genotype by sex. In men (Figure 1B), however, there was a significant main effect of childhood abuse exposure (F1, 423 = 8.20, p = 0.004) as well as a significant interaction effect of childhood abuse exposure by rs110402 genotype (F2,423 = 3.50, p = 0.031), whereas there was no main effect of the genotype. Specifically, men homozygous for the A allele were most protected from developing depression after childhood abuse.

Bottom Line: In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men.In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure.This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine Atlanta, GA, USA.

ABSTRACT
Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

No MeSH data available.


Related in: MedlinePlus