Center for the Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Transl Psychiatry. 2020 Jan 16;10(1):6. doi: 10.1038/s41398-020-0704-2.
Postpartum depression (PPD) affects up to 20% of mothers and has negative consequences for both mother and child. Although exposure to psychosocial stress during pregnancy and abnormalities in the hypothalamic pituitary adrenal (HPA) axis have been linked to PPD, molecular changes in the brain that contribute to this disease remain unknown. This study utilized a novel chronic psychosocial stress paradigm during pregnancy (CGS) to investigate the effects of psychosocial stress on maternal behavior, neuroendocrine function, and gene expression changes in molecular regulators of the HPA axis in the early postpartum period. Postpartum female mice exposed to CGS display abnormalities in maternal behavior, including fragmented and erratic maternal care patterns, and the emergence of depression and anxiety-like phenotypes. Dysregulation in postpartum HPA axis function, evidenced by blunted circadian peak and elevation of stress-induced corticosterone levels, was accompanied by increased CRH mRNA expression and a reduction in CRH receptor 1 in the paraventricular nucleus of the hypothalamus (PVN). We further observed decreased PVN expression of nuclear steroid hormone receptors associated with CRH transcription, suggesting these molecular changes could underlie abnormalities in postpartum HPA axis and behavior observed. Overall, our study demonstrates that psychosocial stress during pregnancy induces changes in neuroendocrine function and maternal behavior in the early postpartum period and introduces our CGS paradigm as a viable model that can be used to further dissect the molecular defects that lead to PPD.
产后抑郁症（PPD）影响多达 20%的母亲，并对母亲和孩子都有负面影响。尽管怀孕期间暴露于心理社会压力和下丘脑-垂体-肾上腺（HPA）轴异常与 PPD 有关，但导致这种疾病的大脑分子变化仍不清楚。本研究利用一种新的孕期慢性心理社会应激模型（CGS），研究心理社会应激对产后早期母性行为、神经内分泌功能和 HPA 轴分子调节因子基因表达变化的影响。暴露于 CGS 的产后雌性小鼠表现出母性行为异常，包括母性行为碎片化和不稳定，以及出现抑郁和焦虑样表型。产后 HPA 轴功能失调，表现为昼夜节律峰值减弱和应激诱导的皮质酮水平升高，同时伴随着下丘脑室旁核（PVN）中 CRH mRNA 表达增加和 CRH 受体 1 减少。我们还观察到与 CRH 转录相关的核甾体激素受体在 PVN 中的表达减少，这表明这些分子变化可能是产后 HPA 轴和行为异常的基础。总的来说，我们的研究表明，孕期心理社会应激会导致产后早期神经内分泌功能和母性行为的变化，并引入我们的 CGS 模型作为一种可行的模型，可用于进一步剖析导致 PPD 的分子缺陷。
