Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
Curr Psychiatry Rep. 2024 Apr;26(4):157-165. doi: 10.1007/s11920-024-01490-8. Epub 2024 Mar 12.
Although females are at relatively greater risk for a variety of disorders, including depression, the biological mechanisms underlying this striking health disparity remain unclear. To address this issue, we highlight sex differences in stress susceptibility as a key mechanism potentially driving this effect and describe the interacting inflammatory, hormonal, epigenomic, and social-environmental mechanisms involved.
Using the Social Signal Transduction Theory of Depression as a theoretical framework, women's elevated risk for depression may stem from a tight link between life stress, inflammation, and depression in women. Further, research finds hormonal contraceptive use alters cortisol and inflammatory reactivity to acute stress in ways that may increase depression risk in females. Finally, beyond established epigenetic mechanisms, mothers may transfer risk for depression to their female offspring through stressful family environments, which influence stress generation and stress-related gene expression. Together, these findings provide initial, biologically plausible clues that may help explain the relatively greater risk for depression in females vs. males. Looking forward, much more research is needed to address the longstanding underrepresentation of females in biomedical research on the biology of stress and depression.
综述目的：尽管女性面临着包括抑郁症在内的多种疾病的相对较高风险，但导致这一显著健康差异的生物学机制仍不清楚。为了解决这个问题，我们强调了应激易感性方面的性别差异，这是一个潜在的关键机制，可能导致了这种影响，并描述了涉及的相互作用的炎症、激素、表观遗传和社会环境机制。
最新发现：以抑郁的社会信号转导理论为理论框架，女性患抑郁症的风险较高可能源于女性生活压力、炎症和抑郁之间的紧密联系。此外，研究发现，激素避孕药的使用以可能增加女性抑郁风险的方式改变了皮质醇和对急性应激的炎症反应。最后，除了已确立的表观遗传机制外，母亲可能通过压力大的家庭环境将抑郁风险传递给她们的女性后代，从而影响压力产生和与压力相关的基因表达。这些发现共同提供了一些初步的、有生物学意义的线索，可能有助于解释女性相对于男性患抑郁症的相对较高风险。展望未来，需要进行更多的研究，以解决在压力和抑郁生物学的生物医学研究中长期存在的女性代表性不足的问题。
