重度抑郁症与童年期性虐待中的多巴胺能前额叶纹状体通路：一项多模态神经影像学研究

Dopaminergic frontostriatal pathways in major depressive disorder and childhood sexual abuse: a multimodal neuroimaging investigation.

作者信息

Borchers Lauren R, Dan Rotem, Belleau Emily L, Kaiser Roselinde H, Clegg Rachel, Goer Franziska, Pechtel Pia, Beltzer Miranda, Wooten Dustin, El Fakhri Georges, Normandin Marc D, Pizzagalli Diego A

机构信息

Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.

Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

出版信息

Mol Psychiatry. 2025 Sep 9. doi: 10.1038/s41380-025-03218-3.

DOI:10.1038/s41380-025-03218-3

PMID:40926089

Abstract

Dysregulated dopaminergic signaling has been implicated in the pathophysiology of major depressive disorder (MDD) and childhood sexual abuse (CSA), but inconsistencies abound. In a multimodal PET-functional MRI study, harnessing the highly selective tracer [C]altropane, we investigated dopamine transporter availability (DAT) and resting-state functional connectivity (rsFC) within reward-related regions among 112 unmedicated individuals (MDD: n = 37, MDD/CSA: n = 18; CSA no MDD: n = 14; controls: n = 43). Striatal DAT and seed-based rsFC were assessed in the dorsal and ventral striatum and the ventral tegmental area. We found that MDD, CSA, and their co-occurrence were associated with region-specific DAT abnormalities, which were related to the number of lifetime MDD episodes and the duration of childhood maltreatment. CSA was further associated with lower frontostriatal rsFC. The findings provide compelling evidence of DA dysregulation in MDD and CSA, and highlight potential prevention and treatment targets.

摘要

多巴胺能信号失调与重度抑郁症（MDD）和儿童期性虐待（CSA）的病理生理学有关，但存在诸多不一致之处。在一项多模态PET-功能磁共振成像研究中，我们利用高选择性示踪剂[C]阿曲库铵，调查了112名未接受药物治疗的个体（MDD：n = 37，MDD/CSA：n = 18；CSA无MDD：n = 14；对照组：n = 43）奖励相关区域内的多巴胺转运体可用性（DAT）和静息态功能连接性（rsFC）。在背侧和腹侧纹状体以及腹侧被盖区评估纹状体DAT和基于种子点的rsFC。我们发现，MDD、CSA及其共病与区域特异性DAT异常有关，这些异常与终生MDD发作次数和儿童期虐待持续时间有关。CSA还与较低的额纹状体rsFC相关。这些发现为MDD和CSA中的多巴胺失调提供了有力证据，并突出了潜在的预防和治疗靶点。