Multimodal and multiscale evidence for network-based cortical thinning in major depressive disorder

Junle Li; Rui Wang; Ning Mao; Manli Huang; Shijun Qiu; Jinhui Wang

doi:10.1016/j.neuroimage.2023.120265

Multimodal and multiscale evidence for network-based cortical thinning in major depressive disorder

Neuroimage. 2023 Aug 15:277:120265. doi: 10.1016/j.neuroimage.2023.120265. Epub 2023 Jul 4.

Authors

Junle Li¹, Rui Wang¹, Ning Mao², Manli Huang³, Shijun Qiu⁴, Jinhui Wang⁵

Affiliations

¹ Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China.
² Department of Radiology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
³ Department of Psychiatry, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; The Key Laboratory of Mental Disorder's Management of Zhejiang Province, Hangzhou, China.
⁴ Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong, China.
⁵ Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China; Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China; Center for Studies of Psychological Application, South China Normal University, Guangzhou, China; Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China. Electronic address: jinhui.wang.1982@m.scnu.edu.cn.

PMID: 37414234
DOI: 10.1016/j.neuroimage.2023.120265

Abstract

Background: Major depressive disorder (MDD) is associated with widespread, irregular cortical thickness (CT) reductions across the brain. However, little is known regarding mechanisms that govern spatial distribution of the reductions.

Methods: We combined multimodal MRI and genetic, cytoarchitectonic and chemoarchitectonic data to examine structural covariance, functional synchronization, gene co-expression, cytoarchitectonic similarity and chemoarchitectonic covariance between regions atrophied in MDD.

Results: Regions atrophied in MDD were associated with significantly higher structural covariance, functional synchronization, gene co-expression and chemoarchitectonic covariance. These results were robust against methodological variations in brain parcellation and null model, reproducible in patients and controls, and independent of age at onset of MDD. Despite no significant differences in the cytoarchitectonic similarity, MDD-related CT reductions were susceptible to specific cytoarchitectonic class of association cortex. Further, we found that nodal shortest path lengths to disease epicenters derived from structural (right supramarginal gyrus) and chemoarchitectonic covariance (right sulcus intermedius primus) networks of healthy brains were correlated with the extent to which a region was atrophied in MDD, supporting the transneuronal spread hypothesis that regions closer to the epicenters are more susceptible to MDD. Finally, we showed that structural covariance and functional synchronization among regions atrophied in MDD were mainly related to genes enriched in metabolic and membrane-related processes, driven by genes in excitatory neurons, and associated with specific neurotransmitter transporters and receptors.

Conclusions: Altogether, our findings provide empirical evidence for and genetic and molecular insights into connectivity-constrained CT thinning in MDD.

Keywords: Brain connectivity; Cortical thickness; Cytoarchitecture; Gene; Magnetic resonance imaging; Major depressive disorder.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain
Cerebral Cortex / diagnostic imaging
Cerebral Cortical Thinning
Depressive Disorder, Major* / diagnostic imaging
Humans
Magnetic Resonance Imaging / methods