Neuroimmune transcriptome changes in brains of psychiatric and neurological disorder patients

Abstract

Neuroinflammation has been implicated in multiple brain disorders but the extent and the magnitude of change in immune-related genes (IRGs) across distinct brain disorders has not been directly compared. We curated 1,275 IRGs and investigated their expression changes in 2,467 postmortem brains of controls and patients with six major brain disorders, including schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer's disease (AD), and Parkinson's disease (PD). More than 60% of the IRGs had significantly altered expression in at least one of the six disorders. The differentially expressed immune-related genes (dIRGs) shared across disorders were mainly related to innate immunity. Moreover, we systematically evaluated sex, tissue, and cell type for immune alterations in different neuropsychiatric disorders. Co-expression networks revealed that neuroimmune systems interacted with neuronal-systems, both of which contribute to the risk of disorders. However, only a few genes with expression changes have also been identified as containing risk variants of genome-wide association studies. The transcriptome alterations at gene and network levels may clarify the immune-related pathophysiology and redefine neuropsychiatric and neurological disorders.

The role of glial cells in mental illness: a systematic review on astroglia and microglia as potential players in schizophrenia and its cognitive and emotional aspects

“…Moreover, the same working group found associations between schizophrenia and genes with important roles in immunity, in line with observational and clinical studies highlighting the connections between immune and inflammatory processes in psychiatric disorders (Benros et al, 2012;Smyth and Lawrie, 2013;Kroken et al, 2018;Hughes and Ashwood, 2020). More recently, research on psychiatric and neurological disorders has increasingly pointed to the neuralimmune interface as potential source of disease markers, thereby enabling the identification of new neurobiological targets (Afridi et al, 2021;Chen et al, 2023).…”

Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis

“…Therefore, specific neuropathologies associated with AD and Parkinson's disease (PD), may be an initial trigger of the proinflammatory response which ultimately impacts on systemic functions and gut microbes. It is also noteworthy that the same study reported clustering of innate immune transcripts between autism spectrum disorder (ASD) and neurological disorders (AD, PD) rather than psychiatric disorders (bipolar disorder [BD], schizophrenia [SCZ], major depressive disorder [MDD]) (Chen et al, 2022). The grouping of ASD with neurological diseases is unexpected, given that it is considered to be a neurodevelopmental disorder.…”

“…A recent analysis of immune-related gene expression in post mortem brain samples from several neuropsychiatric disorders demonstrated neuroimmune dysregulation was more prominent in neurological disorders, particularly Alzheimer's disease (AD), than in psychiatric disorders (Chen et al, 2022). Therefore, specific neuropathologies associated with AD and Parkinson's disease (PD), may be an initial trigger of the proinflammatory response which ultimately impacts on systemic functions and gut microbes.…”

“…analysis by Chen et al (2022). This may suggest that host genetics influencing immunity may contribute to changes in the gut microbiome observed in psychosis (Munawar et al, 2021;Nuncio-Mora et al, 2023), although the several genes which have been associated with schizophrenia may also contribute to a disrupted gut microbiome (Martins-Silva et al, 2021).…”