Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Depress Anxiety. 2013 Mar;30(3):251-8. doi: 10.1002/da.22037. Epub 2012 Dec 28.
A growing literature indicates that genetic variation, in combination with adverse early life experiences, shapes risk for later mental illness. Recent work also suggests that molecular variation at the ADCYAP1R1 locus is associated with posttraumatic stress disorder (PTSD) in women. We sought to test whether childhood maltreatment (CM) interacts with ADCYAP1R1 genotype to predict PTSD in women.
Data were obtained from 495 adult female participants from the Detroit Neighborhood Health Study. Genotyping of rs2267735, an ADCYAP1R1 variant, was conducted via TaqMan assay. PTSD, depression, and CM exposure were assessed via structured interviews. Main and interacting effects of ADCYAP1R1 and CM levels on past month PTSD and posttraumatic stress (PTS) severity were examined using logistic regression and a general linear model, respectively. As a secondary analysis, we also assessed main and interacting effects of ADCYAP1R1 and CM variation on risk of past-month depression diagnosis and symptom severity.
No significant main effects were observed for ADCYAP1R1 genotype on either PTSD/PTS severity. In contrast, a significant ADCYAP1R1 × CM interaction was observed for both past month PTSD and PTS severity, with carriers of the "C" allele showing enhanced risk for these outcomes among women exposed to CM. No significant main or interaction effects were observed for past month depression/depression severity.
Genetic variation at the ADCYAP1R1 locus interacts with CM to shape risk of later PTSD, but not depression, among women. The molecular mechanisms contributing to this interaction require further investigation.
越来越多的文献表明,遗传变异与不良的早期生活经历相结合,会增加患精神疾病的风险。最近的研究还表明,ADCYAP1R1 基因座的分子变异与女性创伤后应激障碍(PTSD)有关。我们试图检验童年期虐待(CM)是否与 ADCYAP1R1 基因型相互作用,从而预测女性 PTSD 的发生。
本研究数据来自底特律社区健康研究的 495 名成年女性参与者。通过 TaqMan 分析对 rs2267735(ADCYAP1R1 变体)进行基因分型。通过结构访谈评估 PTSD、抑郁和 CM 暴露情况。使用逻辑回归和一般线性模型分别评估 ADCYAP1R1 和 CM 水平对过去一个月 PTSD 和创伤后应激(PTS)严重程度的主要和交互作用。作为二次分析,我们还评估了 ADCYAP1R1 和 CM 变异对过去一个月抑郁诊断和症状严重程度的风险的主要和交互作用。
ADCYAP1R1 基因型对 PTSD/PTS 严重程度均无显著的主要作用。相比之下,ADCYAP1R1 和 CM 之间存在显著的相互作用,携带“C”等位基因的个体在经历 CM 后,患这些疾病的风险增加。对于过去一个月的抑郁/抑郁严重程度,均未观察到显著的主要或交互作用。
ADCYAP1R1 基因座的遗传变异与 CM 相互作用,增加了女性日后患 PTSD 的风险,但对抑郁没有影响。导致这种相互作用的分子机制需要进一步研究。