Jensen Kristian H Reveles, Dam Vibeke H, Köhler-Forsberg Kristin, Ozenne Brice, Stenbæk Dea S, Ganz Melanie, Fisher Patrick MacDonald, Frokjaer Vibe Gedsoe, Knudsen Gitte M, Jørgensen Martin Balslev
Neurobiology Research Unit and BrainDrugs, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Neurobiology Research Unit and BrainDrugs, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
J Psychiatr Res. 2025 Jan;181:197-205. doi: 10.1016/j.jpsychires.2024.11.043. Epub 2024 Nov 23.
Serotonin reuptake inhibitors have been reported to increase hippocampal volume and improve memory function in patients with Major depressive disorder (MDD). The postsynaptic 5-HT4 receptor (5-HT4R) is involved in hippocampal development, familial risk for depression and depressive pathology. In an open-label trial with 91 patients (72% female, mean 27.2 years) with MDD, we investigated the relation between changes in hippocampal volume, 5-HT4R, and verbal memory during 12 weeks treatment with 10-20 mg escitalopram. Depression severity, verbal memory, MRI-determined hippocampus volume and PET-determined 5-HT4R were measured pretreatment. Forty-three patients were rescanned at week 8. HAMD was reassessed at week 8 and together with verbal memory at week 12. We used mixed-effects models and linear regressions. We estimated a 27 mm (p = 0.086) reduction in mean hippocampus volume over the course of eight weeks. In patients clinically responding to treatment, we estimated a 45 mm reduction (p = 0.019), 8 mm increase in non-responders (p = 0.78), and a 52 mm group difference (p = 0.12). Hippocampal 5-HT4 receptor binding before treatment and at week eight was negatively associated with hippocampal volume in females, regardless of treatment response (p-values≤0.006). However, no clear evidence for an association in males or sex interaction could be established (p-values≥0.16). Although the hippocampus volume did not increase with treatment, we found a decrease in clinically responsive patients. Our findings suggest an association between 5-HT4R signalling and changes in hippocampal volume in females with MDD during antidepressant treatment, highlighting the need for further investigation into the role of serotonergic mechanisms in hippocampal plasticity.
据报道，血清素再摄取抑制剂可增加重度抑郁症（MDD）患者的海马体积并改善记忆功能。突触后5-羟色胺4受体（5-HT4R）参与海马发育、抑郁症家族风险和抑郁病理过程。在一项针对91例MDD患者（72%为女性，平均年龄27.2岁）的开放标签试验中，我们研究了在使用10-20mg艾司西酞普兰治疗12周期间，海马体积变化、5-HT4R与言语记忆之间的关系。在治疗前测量了抑郁严重程度、言语记忆、MRI测定的海马体积和PET测定的5-HT4R。43例患者在第8周进行了再次扫描。在第8周重新评估了汉密尔顿抑郁量表（HAMD），并在第12周与言语记忆一起进行了评估。我们使用了混合效应模型和线性回归。我们估计在八周的过程中平均海马体积减少了27mm（p = 0.086）。在临床对治疗有反应的患者中，我们估计减少了45mm（p = 0.019），无反应者增加了8mm（p = 0.78），组间差异为52mm（p = 0.12）。无论治疗反应如何，治疗前和第8周时女性海马5-HT4受体结合与海马体积呈负相关（p值≤0.006）。然而，在男性中未发现明确的关联证据或性别相互作用（p值≥0.16）。虽然海马体积并未随治疗增加，但我们发现临床有反应的患者海马体积减少。我们的研究结果表明，在抗抑郁治疗期间，5-HT4R信号与MDD女性患者海马体积变化之间存在关联，突出了进一步研究血清素能机制在海马可塑性中的作用的必要性。
