Dai Haowei, Niu Lijing, Peng Lanxin, Li Qian, Zhang Jiayuan, Chen Keyin, Wang Xingqin, Huang Ruiwang, Lee Tatia M C, Zhang Ruibin
Laboratory of Cognitive Control and Brain Health, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, PRC China.
Department of Neurosurgery, Institute of Brain Diseases, Nanfang Hospital of Southern Medical University, Guangzhou, PRC China.
Psychol Med. 2025 Mar 5;55:e71. doi: 10.1017/S0033291725000418.
Numerous studies have explored the relationship between brain aging and major depressive disorder (MDD) and attempted to explain the phenomenon of faster brain aging in patients with MDD from multiple perspectives. However, a major challenge in this field is elucidating the ontological basis of these changes. Here, we aimed to explore the relationship between brain structural changes in MDD-related brain aging and neurotransmitter expression levels and transcriptomics.
Imaging data from 670 Japanese participants (MDD: health controls = 233:437) and the support vector regression model were utilized to predict and compare brain age between MDD patients and healthy controls. A map of differences in cortical thickness was generated, furthermore, spatial correlation analysis with neurotransmitters and correlation analysis with gene expression were performed.
The degree of brain aging was found to be significantly higher in patients with MDD. Moreover, significant cortical thinning was observed in the left ventral area, and premotor eye field in patients with MDD. A significant correlation was observed between MDD-related cortical thinning and neurotransmitter receptors/transporters, including dopaminergic, serotonergic, and glutamatergic systems. Enriched Gene Ontology terms, including protein binding, plasma membrane, and protein processing, contribute to MDD-related cortical thinning.
The findings of this study provide further evidence that patients with MDD experience more severe brain aging, deepening our understanding of the underlying neural mechanisms and genetic basis of the brain changes involved. Additionally, these findings hold promise for the development of interventions aimed at preventing further deterioration in MDD-related brain aging, thus offering potential therapeutic avenues.
众多研究探讨了大脑衰老与重度抑郁症（MDD）之间的关系，并试图从多个角度解释MDD患者大脑衰老加速的现象。然而，该领域的一个主要挑战是阐明这些变化的本体论基础。在此，我们旨在探讨与MDD相关的大脑衰老中的大脑结构变化与神经递质表达水平及转录组学之间的关系。
利用来自670名日本参与者（MDD：健康对照 = 233：437）的影像数据和支持向量回归模型来预测和比较MDD患者与健康对照之间的脑龄。生成了皮质厚度差异图，此外，还进行了与神经递质的空间相关性分析以及与基因表达的相关性分析。
发现MDD患者的大脑衰老程度显著更高。此外，在MDD患者中观察到左侧腹侧区域和运动前眼区有明显的皮质变薄。在与MDD相关的皮质变薄与神经递质受体/转运体之间观察到显著相关性，包括多巴胺能、血清素能和谷氨酸能系统。包括蛋白质结合、质膜和蛋白质加工在内的富集基因本体术语促成了与MDD相关的皮质变薄。
本研究结果提供了进一步证据，表明MDD患者经历更严重的大脑衰老，加深了我们对所涉及大脑变化的潜在神经机制和遗传基础的理解。此外，这些发现有望为开发旨在预防与MDD相关的大脑衰老进一步恶化的干预措施提供依据，从而提供潜在的治疗途径。
