RNA-Seq Reaveals Gene Sets Altered Across Brain Regions in Schizophrenia, Bipolar Disorder & MDD

from the Psychiatry Advisor by Tori Rodriguez, MA, LPC –

rna-seqA large RNA sequencing study by scientists at Johns Hopkins University School of Medicine has identified gene sets that are consistently dysregulated across brain regions in schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). The findings were published in September 2016 in Translational Psychiatry.

Of the polymorphisms that have been linked with the risk of SCZ, BD, or MDD in genome-wide association studies (GWAS), the most informative ones similarly predict all 3 disorders. Previous functional analysis determined that “pathways that regulate histone methylation and thereby gene transcription are the most strongly implicated on the basis of the shared genetics across the three disorders, followed by immune and signaling pathways,” though their impact on gene expression in the brain has not been elucidated, wrote the authors of the current study.

The majority of postmortem research that has examined functionally related gene sets has been limited to a single disorder or region of the brain, and core processes that are shared across diagnoses and brain regions are unclear. Deficits related to psychiatric disorders have been identified in almost every brain region, ranging from gray and white matter deficits in the superior temporal gyrus, left medial temporal lobe, frontal temporal lobe, and occipital lobe in schizophrenia; to reduced gray matter in the frontal temporal lobe in BD; and decreased gray matter volume in the orbitofrontal cortex in MDD. Various deficits in structure, connectivity, and gene expression have also been found across disorders, suggesting that molecular deficits in such disorders likely impact the entire brain.

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Darby MM, Yolken RH, Sabunciyan S. (2016) Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders. Transl Psychiatry 6(9):e890. [article]

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