Transcriptional Patterns of Functional Connectivity Associated With Somatic Symptoms in Major Depressive Disorder

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Somatic symptoms are prevalent in major depressive disorder (MDD).
• The neurobiological and gene expression underpinnings of these symptoms remain unclear.
• Understanding these mechanisms is crucial for developing targeted treatments.

Purpose of the Study:

• To investigate the relationship between functional connectivity (FC) and somatic symptoms in MDD patients.
• To explore the gene expression patterns associated with FC in the context of somatic symptoms.
• To identify potential biological pathways linking brain activity and physical manifestations of depression.

Main Methods:

• Analysis of a multicenter magnetic resonance imaging dataset from 417 MDD patients.
• Correlation analysis between functional connectivity (FC) and somatic symptom severity.
• Integration of gene expression data (Allen Human Brain Atlas) with FC using partial least squares regression.
• Functional enrichment analysis of genes linked to FC.

Main Results:

• Positive associations were found between FC (medial cerebellum to cortical regions; parietal cortex to prefrontal and temporal regions) and somatic symptom severity.
• Connectome-transcriptome analysis revealed 1120 genes spatially correlated with FC.
• These genes were predominantly enriched in synapses and ion channels.

Conclusions:

• Functional connectivity alterations in specific brain regions are associated with somatic symptom severity in MDD.
• Gene expression variations, particularly in synaptic translation and ion channels, may contribute to the observed FC patterns.
• These findings offer insights into the neurobiological basis of somatic symptoms in depression.