Reduced hippocampal volume occurs in major depressive disorder (MDD), potentially due to elevated glucocorticoids from an overactivated hypothalamus–pituitary–adrenal (HPA) axis. To examine this in humans, hippocampal volume and hypothalamus (HPA axis) metabolism was quantified in participants with MDD before and after antidepressant treatment. 65 participants (n = 24 males, n = 41 females) with MDD were treated in a double-blind, randomized clinical trial of escitalopram. Participants received simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) before and after treatment. Linear mixed models examined the relationship between hippocampus/dentate gyrus volume and hypothalamus metabolism. Chi-squared tests and multivariable logistic regression examined the association between hippocampus/dentate gyrus volume change direction and hypothalamus activity change direction with treatment. Multiple linear regression compared these changes between remitter and non-remitter groups. Covariates included age, sex, and treatment type. No significant linear association was found between hippocampus/dentate gyrus volume and hypothalamus metabolism. 62% (38 of 61) of participants experienced a decrease in hypothalamus metabolism, 43% (27 of 63) of participants demonstrated an increase in hippocampus size (51% [32 of 63] for the dentate gyrus) following treatment. No significant association was found between change in hypothalamus activity and change in hippocampus/dentate gyrus volume, and this association did not vary by sex, medication, or remission status. As this multimodal study, in a cohort of participants on standardized treatment, did not find an association between hypothalamus metabolism and hippocampal volume, it supports a more complex pathway between hippocampus neurogenesis and hypothalamus metabolism changes in response to treatment.

重度抑郁症（MDD）患者海马体积减少，可能是由于下丘脑-垂体-肾上腺（HPA）轴过度激活导致糖皮质激素升高所致。为了在人类中检验这一点，我们对 MDD 参与者在抗抑郁治疗前后的海马体积和下丘脑（HPA 轴）代谢进行了量化。 65 名患有 MDD 的参与者（n = 24 名男性，n = 41 名女性）接受了艾司西酞普兰的双盲、随机临床试验的治疗。参与者在治疗前后同时接受正电子发射断层扫描（PET）/磁共振成像（MRI）。线性混合模型检查了海马/齿状回体积与下丘脑代谢之间的关系。卡方检验和多变量逻辑回归检查了海马/齿状回体积变化方向和下丘脑活动变化方向与治疗之间的关联。多元线性回归比较了汇款人和非汇款人组之间的这些变化。协变量包括年龄、性别和治疗类型。海马/齿状回体积与下丘脑代谢之间没有发现显着的线性相关性。 62%（61 人中的 38 人）的下丘脑代谢下降，43%（63 人中的 27 人）治疗后海马体大小增加（51%（63 人中的 32 人）海马体大小增加）。下丘脑活动的变化与海马/齿状回体积的变化之间没有发现显着的关联，并且这种关联不因性别、药物或缓解状态而变化。由于这项多模态研究在一组接受标准化治疗的参与者中没有发现下丘脑代谢与海马体积之间的关联，因此它支持海马神经发生和下丘脑代谢变化对治疗的反应之间存在更复杂的途径。