Harvard Medical School, Department of Psychiatry, Brigham and Women's Hospital, Connors Center for Women's Health and Gender Biology, USA.
J Affect Disord. 2011 Jun;131(1-3):379-87. doi: 10.1016/j.jad.2010.11.024. Epub 2010 Dec 22.
Women have approximately twice the risk of major depressive disorder (MDD) than men, yet this difference remains largely unexplained. Previous MDD research suggests high rates of endocrine dysfunction, which may be related to deficits in brain activity in stress response circuitry [hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC)]. This functional magnetic resonance imaging (fMRI) study investigated the relationship between hypothalamic-pituitary-gonadal (HPG)-axis hormones and stress response circuitry dysfunction in MDD in women.
During the late follicular/midcycle phase of the menstrual cycle, female participants (10 with extensive histories of MDD, in remission, 10 healthy controls) were scanned while viewing negative and neutral arousal pictures. Group differences in blood oxygen-level dependent (BOLD) signal changes were analyzed using SPM2. Baseline gonadal hormones included estradiol, progesterone, and testosterone.
fMRI results showed greater BOLD signal intensity changes in controls versus MDD in hypothalamus, amygdala, hippocampus, OFC, ACC, and subgenual ACC, findings unrelated to medication status. MDD women had a lower serum estradiol and higher serum progesterone compared to controls. Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone.
Generalizability of our findings is limited by small sample size and restriction to females, although this did not affect the internal validity of the results.
Hypoactivation of the stress response circuitry in MDD women is associated with dysregulation of the HPG-axis. Associations between brain activity deficits and hormonal disruption in MDD may ultimately contribute to understanding sex differences in MDD.
女性患重度抑郁症（MDD）的风险约为男性的两倍，但这种差异在很大程度上仍未得到解释。先前的 MDD 研究表明，内分泌功能障碍的发生率较高，这可能与应激反应回路[下丘脑、杏仁核、海马体、前扣带回皮质（ACC）、眶额皮质（OFC）]中的大脑活动缺陷有关。这项功能磁共振成像（fMRI）研究调查了女性 MDD 中下丘脑-垂体-性腺（HPG）轴激素与应激反应回路功能障碍之间的关系。
在月经周期的晚期卵泡/中期阶段，女性参与者（10 名有广泛 MDD 病史且缓解，10 名健康对照）在观看负面和中性唤醒图片时接受扫描。使用 SPM2 分析血氧水平依赖（BOLD）信号变化的组间差异。基线性腺激素包括雌二醇、孕酮和睾酮。
fMRI 结果显示，与 MDD 相比，对照组的下丘脑、杏仁核、海马体、OFC、ACC 和 subgenual ACC 的 BOLD 信号强度变化更大，这些发现与药物状态无关。MDD 女性的血清雌二醇水平较低，孕酮水平较高，与对照组相比。MDD 患者下丘脑、subgenual ACC、杏仁核和 OFC 的低激活与低雌二醇和高孕酮有关。
我们的研究结果的普遍性受到样本量小和仅限于女性的限制，尽管这并没有影响结果的内部有效性。
MDD 女性应激反应回路的低激活与 HPG 轴失调有关。MDD 中大脑活动缺陷与激素紊乱之间的关联最终可能有助于理解 MDD 中的性别差异。
