Limits...
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 subtype of childhood abuse exposure on current depressive symptoms (N = 1058). (A) There was a significant interaction of moderate to severe physical abuse with rs110402 genotype (F2,1058 = 5.45, p = 0.004). The genotype distribution was as follows: AA = 58, AG = 372, GG = 402 for the none-mild childhood abuse exposure group and AA = 14, AG = 103, GG = 110 for the moderate-severe childhood abuse exposure group. (B) There was no significant interaction of moderate to severe sexual abuse with rs110402 genotype. The genotype distribution was as follows: AA = 57, AG = 364, GG = 366 for the none-mild childhood abuse exposure group and AA = 15, AG = 111, GG = 145 for the moderate-severe childhood abuse exposure group. (C) There was no significant interaction of moderate to severe emotional abuse with rs110402 genotype. The genotype distribution was as follows: AA = 60, AG = 390, GG = 409 for the none-mild childhood abuse exposure group and AA = 12, AG = 85, GG = 103 for the moderate-severe childhood abuse exposure group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2821197&req=5

Figure 2: Interaction of CRHR1 rs110402 genotype and subtype of childhood abuse exposure on current depressive symptoms (N = 1058). (A) There was a significant interaction of moderate to severe physical abuse with rs110402 genotype (F2,1058 = 5.45, p = 0.004). The genotype distribution was as follows: AA = 58, AG = 372, GG = 402 for the none-mild childhood abuse exposure group and AA = 14, AG = 103, GG = 110 for the moderate-severe childhood abuse exposure group. (B) There was no significant interaction of moderate to severe sexual abuse with rs110402 genotype. The genotype distribution was as follows: AA = 57, AG = 364, GG = 366 for the none-mild childhood abuse exposure group and AA = 15, AG = 111, GG = 145 for the moderate-severe childhood abuse exposure group. (C) There was no significant interaction of moderate to severe emotional abuse with rs110402 genotype. The genotype distribution was as follows: AA = 60, AG = 390, GG = 409 for the none-mild childhood abuse exposure group and AA = 12, AG = 85, GG = 103 for the moderate-severe childhood abuse exposure group.

Mentions: In the combined gender sample, only the interaction of physical abuse with rs110402 but not with the presence of emotional or sexual abuse was statistically significant (Figure 2). We observed significant effects of exposure to all three types of abuse on depressive symptoms (physical abuse F1,1058 = 17.5, p < 0.001, sexual abuse F1,1058 = 11.7, p = 0.001, emotional abuse F1,1058 = 72.7, p < 0.001). A significant main effect of rs110402 on depressive symptoms was seen in all three analyses (p < 0.05). The significant interaction of the SNP with exposure to childhood abuse remained only with the presence of physical abuse (F2,1058 = 5.45, p = 0.004). To exclude that these results were due to different distribution of types of abuse between the sexes, we reran analyses in the male subsample and, again, only the interaction with physical abuse (F2,423 = 4.1, p = 0.018), but not the other two abuse types (F2,423 = 0.09, p = 0.91 for sexual abuse and F2,423 = 1.43, p = 0.24 for emotional abuse) was statistically significant. In women, none of the interactions reached statistical significance.


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 subtype of childhood abuse exposure on current depressive symptoms (N = 1058). (A) There was a significant interaction of moderate to severe physical abuse with rs110402 genotype (F2,1058 = 5.45, p = 0.004). The genotype distribution was as follows: AA = 58, AG = 372, GG = 402 for the none-mild childhood abuse exposure group and AA = 14, AG = 103, GG = 110 for the moderate-severe childhood abuse exposure group. (B) There was no significant interaction of moderate to severe sexual abuse with rs110402 genotype. The genotype distribution was as follows: AA = 57, AG = 364, GG = 366 for the none-mild childhood abuse exposure group and AA = 15, AG = 111, GG = 145 for the moderate-severe childhood abuse exposure group. (C) There was no significant interaction of moderate to severe emotional abuse with rs110402 genotype. The genotype distribution was as follows: AA = 60, AG = 390, GG = 409 for the none-mild childhood abuse exposure group and AA = 12, AG = 85, GG = 103 for the moderate-severe childhood abuse exposure group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Interaction of CRHR1 rs110402 genotype and subtype of childhood abuse exposure on current depressive symptoms (N = 1058). (A) There was a significant interaction of moderate to severe physical abuse with rs110402 genotype (F2,1058 = 5.45, p = 0.004). The genotype distribution was as follows: AA = 58, AG = 372, GG = 402 for the none-mild childhood abuse exposure group and AA = 14, AG = 103, GG = 110 for the moderate-severe childhood abuse exposure group. (B) There was no significant interaction of moderate to severe sexual abuse with rs110402 genotype. The genotype distribution was as follows: AA = 57, AG = 364, GG = 366 for the none-mild childhood abuse exposure group and AA = 15, AG = 111, GG = 145 for the moderate-severe childhood abuse exposure group. (C) There was no significant interaction of moderate to severe emotional abuse with rs110402 genotype. The genotype distribution was as follows: AA = 60, AG = 390, GG = 409 for the none-mild childhood abuse exposure group and AA = 12, AG = 85, GG = 103 for the moderate-severe childhood abuse exposure group.
Mentions: In the combined gender sample, only the interaction of physical abuse with rs110402 but not with the presence of emotional or sexual abuse was statistically significant (Figure 2). We observed significant effects of exposure to all three types of abuse on depressive symptoms (physical abuse F1,1058 = 17.5, p < 0.001, sexual abuse F1,1058 = 11.7, p = 0.001, emotional abuse F1,1058 = 72.7, p < 0.001). A significant main effect of rs110402 on depressive symptoms was seen in all three analyses (p < 0.05). The significant interaction of the SNP with exposure to childhood abuse remained only with the presence of physical abuse (F2,1058 = 5.45, p = 0.004). To exclude that these results were due to different distribution of types of abuse between the sexes, we reran analyses in the male subsample and, again, only the interaction with physical abuse (F2,423 = 4.1, p = 0.018), but not the other two abuse types (F2,423 = 0.09, p = 0.91 for sexual abuse and F2,423 = 1.43, p = 0.24 for emotional abuse) was statistically significant. In women, none of the interactions reached statistical significance.

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