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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

Effect of CRHR1 rs110402 on cortisol response in the dexamethasone/CRH test in women (N = 53) versus men (N = 25). Graph depicts mean plasma cortisol concentrations (μg/dl) in subjects grouped according to rs110402 allele status (GG, AG, AA). Subjects with 1 or 2 A alleles (AG or AA) were pooled for statistical analysis and compared with subjects carrying GG-alleles (see text). (A) In women, repeated measures ANOVA only revealed a significant main effect for the time factor (F10, 500 = 68.486, p < 0.001), indicating similar increases in cortisol concentrations in all groups. (B) In men, repeated measures ANOVA revealed a significant interaction of time by genotype (F10,230 = 2.225, p = 0.017), indicating decreased response in men carrying the A allele compared to men homozygous GG.
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Figure 3: Effect of CRHR1 rs110402 on cortisol response in the dexamethasone/CRH test in women (N = 53) versus men (N = 25). Graph depicts mean plasma cortisol concentrations (μg/dl) in subjects grouped according to rs110402 allele status (GG, AG, AA). Subjects with 1 or 2 A alleles (AG or AA) were pooled for statistical analysis and compared with subjects carrying GG-alleles (see text). (A) In women, repeated measures ANOVA only revealed a significant main effect for the time factor (F10, 500 = 68.486, p < 0.001), indicating similar increases in cortisol concentrations in all groups. (B) In men, repeated measures ANOVA revealed a significant interaction of time by genotype (F10,230 = 2.225, p = 0.017), indicating decreased response in men carrying the A allele compared to men homozygous GG.

Mentions: We first tested the hypothesis that there are sex differences in the effects of the protective CRHR1 rs110402 A allele on cortisol response to the dexamethasone/CRH test. For statistical analyses, we pooled subjects carrying 1 or 2 A alleles (AG + AA) and compared A allele carriers with GG carriers. For informative reasons, rs110402 subgroups (AA, AG, and GG) are presented separately in Figure 3. For women (Figure 3A), repeated measures ANOVA revealed a significant main effect of the time factor, indicating similar increases in cortisol concentrations after CRH injection in all groups (F10, 500 = 68.486, p < 0.001). However, there was neither a significant main effect of genotype, nor a genotype by time interaction effect, on plasma cortisol concentrations in women. For men (Figure 3B), repeated measures ANOVA revealed a significant interaction effect of genotype by time (F10,230 = 2.225, p = 0.017): Men carrying one or two rs110402 A allele demonstrated markedly decreased plasma cortisol responses in the dexamethasone/CRH test compared to men who were homozygous rs110402 GG-allele carriers. All effects remained significant when controlling for current or lifetime major depression.


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)

Effect of CRHR1 rs110402 on cortisol response in the dexamethasone/CRH test in women (N = 53) versus men (N = 25). Graph depicts mean plasma cortisol concentrations (μg/dl) in subjects grouped according to rs110402 allele status (GG, AG, AA). Subjects with 1 or 2 A alleles (AG or AA) were pooled for statistical analysis and compared with subjects carrying GG-alleles (see text). (A) In women, repeated measures ANOVA only revealed a significant main effect for the time factor (F10, 500 = 68.486, p < 0.001), indicating similar increases in cortisol concentrations in all groups. (B) In men, repeated measures ANOVA revealed a significant interaction of time by genotype (F10,230 = 2.225, p = 0.017), indicating decreased response in men carrying the A allele compared to men homozygous GG.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effect of CRHR1 rs110402 on cortisol response in the dexamethasone/CRH test in women (N = 53) versus men (N = 25). Graph depicts mean plasma cortisol concentrations (μg/dl) in subjects grouped according to rs110402 allele status (GG, AG, AA). Subjects with 1 or 2 A alleles (AG or AA) were pooled for statistical analysis and compared with subjects carrying GG-alleles (see text). (A) In women, repeated measures ANOVA only revealed a significant main effect for the time factor (F10, 500 = 68.486, p < 0.001), indicating similar increases in cortisol concentrations in all groups. (B) In men, repeated measures ANOVA revealed a significant interaction of time by genotype (F10,230 = 2.225, p = 0.017), indicating decreased response in men carrying the A allele compared to men homozygous GG.
Mentions: We first tested the hypothesis that there are sex differences in the effects of the protective CRHR1 rs110402 A allele on cortisol response to the dexamethasone/CRH test. For statistical analyses, we pooled subjects carrying 1 or 2 A alleles (AG + AA) and compared A allele carriers with GG carriers. For informative reasons, rs110402 subgroups (AA, AG, and GG) are presented separately in Figure 3. For women (Figure 3A), repeated measures ANOVA revealed a significant main effect of the time factor, indicating similar increases in cortisol concentrations after CRH injection in all groups (F10, 500 = 68.486, p < 0.001). However, there was neither a significant main effect of genotype, nor a genotype by time interaction effect, on plasma cortisol concentrations in women. For men (Figure 3B), repeated measures ANOVA revealed a significant interaction effect of genotype by time (F10,230 = 2.225, p = 0.017): Men carrying one or two rs110402 A allele demonstrated markedly decreased plasma cortisol responses in the dexamethasone/CRH test compared to men who were homozygous rs110402 GG-allele carriers. All effects remained significant when controlling for current or lifetime major depression.

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