Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

Jiao Li, Jakob Seidlitz, John Suckling, Feiyang Fan, Gong-Jun Ji, Yao Meng, Siqi Yang, Kai Wang, Jiang Qiu, Huafu Chen () and Wei Liao ()
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Jiao Li: University of Electronic Science and Technology of China
Jakob Seidlitz: Children’s Hospital of Philadelphia, Department of Child and Adolescent Psychiatry and Behavioral Science
John Suckling: University of Cambridge, Department of Psychiatry
Feiyang Fan: University of Electronic Science and Technology of China
Gong-Jun Ji: Anhui Medical University
Yao Meng: University of Electronic Science and Technology of China
Siqi Yang: University of Electronic Science and Technology of China
Kai Wang: Anhui Medical University
Jiang Qiu: Southwest University
Huafu Chen: University of Electronic Science and Technology of China
Wei Liao: University of Electronic Science and Technology of China

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Major depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.

Date: 2021
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DOI: 10.1038/s41467-021-21943-5

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