1 Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada.
2 Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
J Psychopharmacol. 2018 Feb;32(2):125-133. doi: 10.1177/0269881117747578. Epub 2018 Feb 6.
There is increasing recognition that women have a higher prevalence of certain psychiatric illnesses, and a differential treatment response and course of illness compared to men. Additionally, clinicians deal with a number of disorders like premenstrual syndrome, premenstrual dysphoric disorder, and postpartum depression, which affect women specifically and for which treatment and biological pathways are still unclear. In this article we highlight recent research which suggests that different biological mechanisms may underlie sex differences in responsiveness to stress. Sex differences are evident at the receptor level; where the corticotropin-releasing factor receptor shows differential coupling to adaptor proteins in males and females. The neuropeptide oxytocin also shows sex-specific effects in a range of social behaviors. It may act as a biomarker in post-traumatic stress disorder where sex differences are evident. Studies in women using hormonal contraception show that some of these oxytocin-mediated effects are likely influenced by sex hormones. In female rats rapid changes in circulating progesterone levels are associated with exaggerated behavioral responses to mild stress and blunted responses to benzodiazepines that could be prevented by acute treatment with low-dose fluoxetine. Perceived barriers in research on women have hindered progress. The development of a sex-specific psychopharmacology as a basis for translating this type of research into clinical practice is vital to improve treatment outcomes for women.
越来越多的人认识到，与男性相比，女性某些精神疾病的患病率更高，治疗反应和疾病过程也存在差异。此外，临床医生还需要处理许多特定于女性的疾病，如经前期综合征、经前期烦躁障碍和产后抑郁症等，这些疾病的治疗和生物学途径尚不清楚。在本文中，我们强调了最近的研究表明，不同的生物学机制可能是导致女性对压力反应存在性别差异的基础。性别差异在受体水平上很明显；促肾上腺皮质激素释放因子受体在男性和女性中与衔接蛋白的偶联存在差异。神经肽催产素在一系列社会行为中也表现出性别特异性效应。它可能作为创伤后应激障碍的生物标志物，在这种疾病中存在性别差异。对使用激素避孕的女性进行的研究表明，这些催产素介导的效应中的一些可能受到性激素的影响。在雌性大鼠中，循环孕酮水平的快速变化与对轻度应激的行为反应过度和苯二氮䓬类药物反应迟钝有关，而急性低剂量氟西汀治疗可以预防这种情况。对女性的研究中存在的感知障碍阻碍了研究进展。开发一种基于这种研究转化为临床实践的性别特异性精神药理学对于改善女性的治疗效果至关重要。
