Peters Jessica R, Schmalenberger Katja M, Eng Ashley G, Stumper Allison, Martel Michelle M, Eisenlohr-Moul Tory A
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
Mol Psychiatry. 2025 Jan;30(1):251-262. doi: 10.1038/s41380-024-02693-4. Epub 2024 Aug 15.
Fluctuations in progesterone (P4) and estradiol (E2) across the menstrual cycle can exert direct effects on biological systems implicated in neuropsychiatric disorders and represent a key biological source of variability in affective, cognitive, and behavioral disorders. Although these cyclical symptoms may be most readily identified when they occur exclusively in relation to the menstrual cycle, as in DSM-5 premenstrual dysphoric disorder, symptom changes of similar magnitude occur in a larger proportion of people with ongoing psychiatric disorders. Studies investigating cyclical regulation of brain and behavior often produce inconsistent results, which may be attributed to a lack of focus on specific hormonal events and individual differences in related sensitivities. We propose a transdiagnostic Dimensional Affective Sensitivity to Hormones across the Menstrual Cycle (DASH-MC) framework, postulating that atypical neural responses to several key hormonal events provoke specific temporal patterns of affective and behavioral change across the menstrual cycle. We review prospective and experimental evidence providing initial support for these dimensions, which include (1) luteal-onset negative affect caused by a sensitivity to E2 or P4 surges (mediated by neuroactive metabolites such as allopregnanolone), typified by irritability and hyperarousal; (2) perimenstrual-onset negative affect caused by a sensitivity to low or falling E2, typified by low mood and cognitive dysfunction; and (3) preovulatory-onset positive affect dysregulation caused by a sensitivity to E2 surges, typified by harmful substance use and other risky reward-seeking. This multidimensional, transdiagnostic framework for hormone sensitivity can inform more precise research on ovarian steroid regulation of psychopathology, including further mechanistic research, diagnostic refinement, and precision psychiatry treatment development. Additionally, given the high rates of hormone sensitivity across affective disorders, the DASH-MC may guide broader insights into the complex neurobiological vulnerabilities driving female-biased affective risk, as well as potential triggers and mechanisms of affective state change in psychiatric disorders.
月经周期中孕酮（P4）和雌二醇（E2）的波动可对涉及神经精神疾病的生物系统产生直接影响，是情感、认知和行为障碍中变异性的关键生物学来源。尽管这些周期性症状在仅与月经周期相关时最容易被识别，如在《精神疾病诊断与统计手册》第5版中的经前烦躁障碍，但在患有持续性精神疾病的人群中，有更大比例的人出现了类似程度的症状变化。研究大脑与行为的周期性调节往往会产生不一致的结果，这可能归因于对特定激素事件缺乏关注以及相关敏感性的个体差异。我们提出了一个跨诊断的月经周期激素维度情感敏感性（DASH-MC）框架，假设对几个关键激素事件的非典型神经反应会引发整个月经周期中情感和行为变化的特定时间模式。我们回顾了前瞻性和实验证据，这些证据为这些维度提供了初步支持，其中包括：（1）对E2或P4激增敏感（由神经活性代谢物如别孕烯醇酮介导）导致的黄体期开始时的消极情绪，表现为易怒和过度觉醒；（2）对低水平或下降的E2敏感导致的围经期开始时的消极情绪，表现为情绪低落和认知功能障碍；（3）对E2激增敏感导致的排卵前开始时的积极情绪失调，表现为有害物质使用和其他危险的寻求奖励行为。这个激素敏感性的多维度、跨诊断框架可以为卵巢类固醇对精神病理学调节的更精确研究提供信息，包括进一步的机制研究、诊断细化和精准精神病学治疗开发。此外，鉴于情感障碍中激素敏感性的高发生率，DASH-MC可能有助于更深入地了解驱动女性偏向情感风险的复杂神经生物学脆弱性，以及精神疾病中情感状态变化的潜在触发因素和机制。
