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Cerebral blood flow changes and their genetic mechanisms in major depressive disorder: a combined neuroimaging and transcriptome study

Published online by Cambridge University Press:  05 January 2023

Xuetian Sun
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
Weisheng Huang
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
Jie Wang
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
Ruoxuan Xu
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
Xiaohan Zhang
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
Jianhui Zhou
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
Jiajia Zhu*
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
Yinfeng Qian*
Affiliation:
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
*
Authors for correspondence: Yinfeng Qian, E-mail: liangminqyf@sohu.com; Jiajia Zhu, E-mail: zhujiajiagraduate@163.com
Authors for correspondence: Yinfeng Qian, E-mail: liangminqyf@sohu.com; Jiajia Zhu, E-mail: zhujiajiagraduate@163.com

Abstract

Background

Extensive research has shown abnormal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) that is a heritable disease. The objective of this study was to investigate the genetic mechanisms of CBF abnormalities in MDD.

Methods

To achieve a more thorough characterization of CBF changes in MDD, we performed a comprehensive neuroimaging meta-analysis of previous literature as well as examined group CBF differences in an independent sample of 133 MDD patients and 133 controls. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial association analyses were conducted to identify genes whose expression correlated with CBF changes in MDD, followed by a set of gene functional feature analyses.

Results

We found increased CBF in the reward circuitry and default-mode network and decreased CBF in the visual system in MDD patients. Moreover, these CBF changes were spatially associated with expression of 1532 genes, which were enriched for important molecular functions, biological processes, and cellular components of the cerebral cortex as well as several common mental disorders. Concurrently, these genes were specifically expressed in the brain tissue, in immune cells and neurons, and during nearly all developmental stages. Regarding behavioral relevance, these genes were associated with domains involving emotion and sensation. In addition, these genes could construct a protein-protein interaction network supported by 60 putative hub genes with functional significance.

Conclusions

Our findings suggest a cerebral perfusion redistribution in MDD, which may be a consequence of complex interactions of a wide range of genes with diverse functional features.

Type
Original Article
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

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