Heim Christine, Bradley Bekh, Mletzko Tanja C, Deveau Todd C, Musselman Dominique L, Nemeroff Charles B, Ressler Kerry J, Binder Elisabeth B
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine Atlanta, GA, USA.
Front Behav Neurosci. 2009 Nov 6;3:41. doi: 10.3389/neuro.08.041.2009. eCollection 2009.
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.
促肾上腺皮质激素释放激素受体1（CRHR1）基因的变异似乎会影响童年创伤后抑郁症的发展。抑郁症在女性中的发病率高于男性。我们研究了CRHR1基因在童年创伤与成人抑郁症关系中的性别差异。我们从一家城市公立医院的候诊室招募了1063名受试者。使用量表评估童年创伤暴露情况和抑郁症状。对受试者的CRHR1基因中的rs110402进行基因分型。对78名受试者的独立样本进行了临床评估、基因分型和地塞米松/促肾上腺皮质激素释放激素（CRH）测试。两项研究的招募年龄范围分别为18 - 77岁和18 - 45岁。在医院样本中，rs110402 A等位基因对男性（N = 424）童年创伤后患抑郁症有保护作用，但对女性（N = 635）没有。在第二个样本中，rs110402 A等位基因仅在男性的地塞米松/CRH测试中与皮质醇反应降低有关。在有童年创伤暴露的A等位基因携带者中，女性的皮质醇反应比男性增加；在没有创伤暴露的A等位基因携带者中没有性别差异。然而，这种影响可能与性别差异本身无关，而是与男性和女性所经历的虐待类型差异有关。在医院样本中观察到CRHR与环境的相互作用，这种相互作用与身体虐待有关，但与性虐待或情感虐待无关。身体虐待是该队列中男性最常见的虐待类型，而性虐待是女性最常遭受的。我们的结果表明，CRHR1基因可能仅调节特定类型的童年创伤对抑郁症的影响。因此，环境暴露中的性别差异可能反映在特定性别的CRHR1与儿童虐待的相互作用中。
