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

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    This study reveals linked brain and blood gene expression patterns in comorbid psychopathology. These findings may help develop new diagnostics and treatments for depressive disorders.

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    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.