Department of Psychiatry & Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States.
Front Endocrinol (Lausanne). 2023 Dec 12;14:1295261. doi: 10.3389/fendo.2023.1295261. eCollection 2023.
The aim of this narrative review is to consolidate knowledge on the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression pathophysiology at different reproductive stages across the female lifespan. Despite growing evidence about the impact of gonadal hormones on mood disorders, no previous review has examined the interaction between such hormonal changes and the HPA axis within the context of depressive disorders in women. We will focus on HPA axis function in depressive disorders at different reproductive stages including the menstrual cycle (e.g., premenstrual dysphoric disorder [PMDD]), perinatally (e.g., postpartum depression), and in perimenopausal depression. Each of these reproductive stages is characterized by vast physiological changes and presents major neuroendocrine reorganization. The HPA axis is one of the main targets of such functional alterations, and with its key role in stress response, it is an etiological factor in vulnerable windows for depression across the female lifespan. We begin with an overview of the HPA axis and a brief summary of techniques for measuring HPA axis parameters. We then describe the hormonal milieu of each of these key reproductive stages, and integrate information about HPA axis function in depression across these reproductive stages, describing similarities and differences. The role of a history of stress and trauma exposure as a contributor to female depression in the context of HPA axis involvement across the reproductive stages is also presented. This review advances the pursuit of understanding common biological mechanisms across depressive disorders among women. Our overarching goal is to identify unmet needs in characterizing stress-related markers of depression in women in the context of hormonal changes across the lifespan, and to support future research in women's mental health as it pertains to pathophysiology, early diagnosis, and treatment targets.
本综述旨在整合下丘脑-垂体-肾上腺（HPA）轴在女性生命各阶段不同生殖期抑郁发病机制中的作用的知识。尽管越来越多的证据表明性腺激素对情绪障碍有影响，但以前没有综述研究过这些激素变化与 HPA 轴在女性抑郁障碍中的相互作用。我们将重点关注不同生殖期抑郁障碍中 HPA 轴的功能，包括月经周期（例如经前烦躁障碍[PMDD]）、围产期（例如产后抑郁症）和围绝经期抑郁症。这些生殖期各有其特点，即存在巨大的生理变化和主要的神经内分泌重组。HPA 轴是这些功能改变的主要靶点之一，它在应激反应中的关键作用使其成为女性生命各阶段易患抑郁症的一个病因。我们首先概述 HPA 轴，并简要总结测量 HPA 轴参数的技术。然后，我们描述这些关键生殖期的激素环境，并整合这些生殖期抑郁障碍中 HPA 轴功能的信息，描述相似点和不同点。还介绍了应激和创伤暴露史作为 HPA 轴参与女性生殖期抑郁症的一个促成因素的作用。本综述推动了对女性抑郁障碍中共同生物学机制的理解。我们的总体目标是确定在女性一生中荷尔蒙变化的背景下，描述与应激相关的抑郁标志物的未满足需求，并为女性心理健康的未来研究提供支持，涉及病理生理学、早期诊断和治疗靶点。
