Brain connectivity and transcriptomic similarity inform abnormal morphometric similarity patterns in first-episode, treatment-naïve major depressive disorder

Kaizhong Xue; Feng Liu; Sixiang Liang; Lining Guo; Yi Shan; Huijuan Xu; Jiao Xue; Yifan Jiang; Yong Zhang; Jie Lu

doi:10.1016/j.jad.2024.11.021

Brain connectivity and transcriptomic similarity inform abnormal morphometric similarity patterns in first-episode, treatment-naïve major depressive disorder

J Affect Disord. 2024 Nov 9:370:519-531. doi: 10.1016/j.jad.2024.11.021. Online ahead of print.

Authors

Kaizhong Xue¹, Feng Liu², Sixiang Liang³, Lining Guo², Yi Shan⁴, Huijuan Xu⁴, Jiao Xue⁴, Yifan Jiang⁵, Yong Zhang⁶, Jie Lu⁷

Affiliations

¹ Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing 100053, China; Department of Radiology, Tianjin Key Lab of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
² Department of Radiology, Tianjin Key Lab of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
³ The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China; Tianjin Anding Hospital, Tianjin 300222, China.
⁴ Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing 100053, China.
⁵ School of Nursing, Tianjin Medical University, Tianjin 300070, China.
⁶ Tianjin Anding Hospital, Tianjin 300222, China. Electronic address: zhangyong@tjmhc.com.
⁷ Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing 100053, China. Electronic address: imaginglu@hotmail.com.

PMID: 39522735
DOI: 10.1016/j.jad.2024.11.021

Abstract

Background: Major depressive disorder (MDD) is associated with disrupted brain structural integration. Morphometric similarity offers a means to capture the coordinated patterns of various structural features. However, it remains unknown whether MDD-related changes can be detected in cortical morphometric similarity through the Morphometric Inverse Divergence (MIND) network. Additionally, the role of brain connectivity in shaping these alterations, and their links to neuroreceptors and gene expression, have yet to be investigated.

Methods: Using the T1-weighted MRI data from 71 patients with first-episode, treatment-naïve MDD and 69 healthy controls, we constructed the MIND network for all participants. We then performed between-group comparisons to investigate abnormalities in the network and spatial relationships between the observed patterns of MIND disruption and the patterns of neuroreceptors were estimated. Network-based spreading was utilized to explore the abnormalities constrained by brain connectivity based on structural, functional, and transcriptional connectome architecture and to further identify potential epicenters of MDD. In addition, partial least squares regression was conducted to examine the associations of gene expression profiles with MIND changes in MDD.

Results: Patients with MDD showed significantly increased MIND in regions associated with sensation and cognition compared with healthy controls, with this altered pattern being influenced by a combination of transcriptional and structural connectivity, and potential epicenters of MDD were identified in the frontal, parietal, and paracentral cortices. Furthermore, the cortical map of case-control differences in MIND was spatially correlated with the cannabinoid CB₁ receptor and the brain-wide expression of a weighted combination of genes. These genes were enriched for neurobiologically relevant pathways and preferentially expressed in different cell classes and cortical layers.

Conclusion: These results highlight the abnormal pattern of morphometric similarity observed in MDD, shedding light on the complex interplay between disrupted macroscale coordinated morphology and microscale molecular organization in MDD.

Keywords: Epicenters; Gene expression; Major depressive disorder; Morphometric Inverse Divergence network; Neuroreceptors.