Walsh E C, Prim J H, Gibson K, Hynd M, Phillips R D, Dichter G S, Nathan M D, Lundegard L, Schiff L, Bizzell J, Belger A, Rubinow D R, Schiller C E
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Department of OBGYN, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
J Affect Disord. 2025 Jun 1;378:340-349. doi: 10.1016/j.jad.2025.01.033. Epub 2025 Jan 19.
Half of perimenopausal women experience depressive symptoms, including anhedonia. Anhedonia is associated with dysregulation of the frontostriatal circuit. Both the frontrostriatal circuit and depression may be regulated by the reproductive hormone estradiol (E2). Here, we present data from a pharmaco-fMRI trial investigating E2 effects on brain activation and anhedonia in those with perimenopause-onset major depression (PO-MDD).
Participants with PO-MDD (n = 16) and those without depression (i.e., Controls; n = 19) received transdermal E2 for three weeks and completed two fMRI sessions (Pre- and Post-E2), and weekly anhedonia assessments. During each fMRI session, neural responses to anticipation and outcomes of monetary rewards were measured.
The PO-MDD group exhibited steeper declines in anhedonia following E2 administration (t(101.95) = -8.7, pFDR < 0.001). Contrary to a priori hypotheses, there were no group differences in striatal activation at baseline nor did striatal activation significantly change with E2 administration in either group. However, exploratory whole-brain analyses revealed a significant Group∗Time interaction in a cluster spanning the right inferior, middle, and precentral gyri during reward anticipation (Z = 2.58 and pFWE < 0.05). From Pre-E2 to Post-E2, PO-MDD showed decreased activation within this cluster (t = 3.0, p < 0.009), whereas the Controls did not (t = 1.89, p = 0.08). Further, following E2 administration, both PO-MDD and Control groups exhibited reduced activation in the cerebellum, inferior and medial frontal gyri, and occipital pole during reward anticipation (Z = 2.58, pFWE < 0.05).
While both anhedonia and right prefrontal activation during anticipatory reward processing were reduced in PO-MDD after three weeks of E2 administration, further research investigating the antidepressant effects of E2 is needed.
围绝经期女性中有一半会出现抑郁症状，包括快感缺失。快感缺失与额纹状体回路失调有关。额纹状体回路和抑郁症都可能受生殖激素雌二醇（E2）调节。在此，我们展示了一项药物功能磁共振成像试验的数据，该试验研究了E2对围绝经期起病的重度抑郁症（PO-MDD）患者大脑激活和快感缺失的影响。
PO-MDD患者（n = 16）和无抑郁者（即对照组；n = 19）接受经皮E2治疗三周，并完成两次功能磁共振成像检查（E2治疗前和治疗后），以及每周一次的快感缺失评估。在每次功能磁共振成像检查期间，测量对金钱奖励预期和结果的神经反应。
PO-MDD组在给予E2后快感缺失下降更为明显（t(101.95) = -8.7，pFDR < 0.001）。与先验假设相反，两组在基线时纹状体激活无差异，且两组给予E2后纹状体激活均无显著变化。然而，探索性全脑分析显示，在奖励预期期间，一个跨越右侧额下回、额中回和中央前回的脑区簇存在显著的组×时间交互作用（Z = 2.58，pFWE < 0.05）。从E2治疗前到治疗后，PO-MDD组该脑区簇内的激活减少（t = 3.0，p < 0.009），而对照组未减少（t = 1.89，p = 0.08）。此外，给予E2后，PO-MDD组和对照组在奖励预期期间小脑、额下回和额内侧回以及枕极的激活均减少（Z = 2.58，pFWE < 0.05）。
虽然给予E2三周后，PO-MDD患者在预期奖励处理过程中的快感缺失和右侧前额叶激活均有所减少，但仍需要进一步研究E2的抗抑郁作用。
