The first decade and beyond of transcriptional profiling in schizophrenia

Abstract

Gene expression changes in brains of individuals with schizophrenia (SZ) have been hypothesized to reflect possible pathways related to pathophysiology and/or medication. Other factors have robust effects on gene expression profiling in brain and possibly influence the schizophrenia transcriptome such as age and pH are examined. Pathways of curated gene expression or gene correlation networks reported in SZ (white matter, apoptosis, neurogenesis, synaptic plasticity, glutamatergic and GABAergic neurotransmission, immune and stress-response, mitochondrial, and neurodevelopment) are not unique to SZ and have been associated with other psychiatric disorders. Suggestions going forward to improve the next decade of profiling: consider multiple brain regions that are carefully dissected, release large datasets from multiple brain regions in controls to better understand neurocircuitry, integrate genetics and gene expression, measure expression variants on genome wide level, peripheral biomarker studies, and analyze the transcriptome across a developmental series of brains. Gene expression, while an important feature of the genomic landscape, requires further systems biology to advance from control brains to a more precise definition of the schizophrenia interactome.

Myelin, myelin-related disorders, and psychosis

“…The finding that so many biologically related genes were down-regulated suggests the possibility that oligodendroglia, the cell type expressing these genes derive in the brain, are dysfunctional or even undergoing apoptosis . Furthermore, there are additional post-mortem studies providing support for OMR abnormalities in schizophrenia (Sequeira et al, 2012;Roussos and Haroutunian, 2014; for review, see Fitzsimmons et al, 2013).…”

Peripheral Biomarkers Revisited: Integrative Profiling of Peripheral Samples for Psychiatric Research

“…However, data analyses that have focused on gene ontology have been used to compare studies. The early-stage studies of gene expression in peripheral samples have been reviewed elsewhere (44). Comprehensive array technologies have frequently been used to explore gene expression patterns to discriminate disease and disease subtypes from control subjects.…”

Genes involved in pruning and inflammation are enriched in a large mega-sample of patients affected by Schizophrenia and Bipolar Disorder and controls

“…The immune hypothesis of SCZ has gained credibility thanks to studies performed in recent years (Krause et al, 2012; Saetre et al, 2007; Sequeira et al, 2012) and especially after the detection of novel functions of the immune molecules in the brain and bidirectional cross-talk between the Immune System(IS) and the Central Nervous System (CNS) (Tian et al, 2012). …”