ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1692921
This article is part of the Research TopicThe Genetic Intersection of Mental and Physical Health: Unraveling Shared Heritable Risk FactorsView all 4 articles
Transcriptomic Decoding of Brain Function and Cerebral Blood Flow Impairments in First-Episode Drug-Naive Patients with Major Depressive Disorder
Provisionally accepted
Miaoqian Tu1
ZL Yu1
Wenwen Song1,2
Xiaomei Shao1
Jingjing Xu3
Jiangnan Lin1,2
Maosheng Xu1,2
Zhijian Cao1,2*- 1Zhejiang Chinese Medical University, Hangzhou, China
- 2Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China
- 3The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China
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Background: Major depressive disorder (MDD) is highly prevalent and severely impacts daily life. The objective of this study is to investigate the genetic mechanisms behind brain function and perfusion abnormalities, measured by the amplitude of low-frequency fluctuations (ALFF) and cerebral blood flow (CBF) in first-episode drug-naive MDD (FEDN-MDD). Methods: In this study, we analyzed ALFF and CBF alterations in 34 FEDN-MDD patients and 32 matched healthy controls (HCs) using multimodal magnetic resonance imaging (MRI). Combined with the Allen Human Brain Atlas, we performed spatial correlation analysis between neuroimaging and transcriptomic data, followed by gene enrichment analysis to identify gene expression patterns associated with ALFF and CBF alterations in FEDN-MDD. Results: Compared to HCs, FEDN-MDD patients exhibited decreased ALFF in the right parahippocampal gyrus, elevated CBF in the right middle frontal gyrus, and reduced CBF in the right superior temporal gyrus. Furthermore, these brain function and perfusion changes were spatially associated with the expression of 1,128 and 1,147 genes, respectively. Importantly, the two gene sets demonstrated both shared and distinct features, primarily related to synaptic plasticity, angiogenesis, and neurovascular coupling (NVC). Conclusions: These findings highlight the correlation between genetic factors and FEDN-MDD, revealing both shared and distinct molecular associations with brain function and perfusion.
Keywords: Major Depressive Disorder, Amplitude of low-frequency fluctuations, cerebral bloodflow, neurovascular coupling, Functional enrichment analysis
Received: 26 Aug 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Tu, Yu, Song, Shao, Xu, Lin, Xu and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhijian Cao, 20001010@zcmu.edu.cn
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