Brain network and blood transcriptomic correlations underpin psychopathological phenotypes: A Preliminary Study

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Depressive disorders and comorbid psychopathologies impact over 12% of the population.
• Systemic biological dysregulations in brain and periphery are known, but the molecular pathobiology is unclear.
• Understanding brain-body molecular links is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the molecular signatures of depressive and comorbid psychopathology.
• To analyze transcriptomic correlations between brain regions (anterior insula and subgenual cingulate) and whole blood.
• To identify shared and distinct molecular underpinnings in brain and blood.

Main Methods:

• Analysis of postmortem brain tissue (anterior insula, subgenual cingulate) and whole blood from 14 donors.
• Examined gene expression/transcriptomic correlations within the brain and between brain and blood.
• Utilized mixed effects analysis to associate gene expression with psychopathology measures.

Main Results:

• Brain regions showed concordant gene expression in ~50% of markers and discordant in <10%.
• Brain-blood correlations were normally distributed, with ~20% concordant and ~20% discordant.
• Comorbid psychopathology associated with upregulation of *TEC*, *OR52E4*, and *OR56B2P* in brain and blood; *IL18R1* and *WIF1* in blood; and downregulation of *TECTB* in blood.

Conclusions:

• Concordant and discordant transcriptomes highlight interconnected brain-blood molecular underpinnings of comorbid psychopathology.
• Identified specific genes (*TEC*, *OR52E4*, *OR56B2P*, *IL18R1*, *WIF1*, *TECTB*) linked to psychopathology.
• Findings provide a framework for developing brain-derived peripheral markers for diagnostics and therapeutics.