Glial cell contribution to schizophrenia refined
medwireNews: An analysis of functional gene sets has helped to define the role of glial cells in schizophrenia.
Variants in gene sets related to known functions of astrocytes and oligodendrocytes were significantly associated with the condition, report Danielle Posthuma (VU University, Amsterdam, the Netherlands) and co-workers.
But against their expectations, the researchers did not detect an association between any of the 19 microglia gene sets studied and schizophrenia, despite previous studies showing activation of microglia in schizophrenia patients.
This suggests “that previously reported microglial changes and neuroinflammatory symptoms involving these genes might represent secondary effects in response to primary schizophrenia-induced pathology,” they write in Schizophrenia Bulletin.
The team used genetic data for 13,689 schizophrenia patients and 18,226 healthy controls. Six of 31 astrocyte gene sets were significantly associated with schizophrenia, as were three of 29 oligodendrocyte gene sets.
The astrocyte gene sets comprised those involved in signal transduction, cell adhesion, and gene transcription, as well as tyrosine kinase signaling, G protein-coupled receptor signaling, and small GTPase-mediated signaling. The researchers say that the latter three processes include molecules “well known to localize and function at the synapse,” so abnormalities could result in impaired modulation of synapse strength by astroctyes.
The significant oligodendrocyte gene sets were involved with lipid metabolism, oxidation–reduction, and gene transcription, aberrations in any of which could compromise the myelin sheath, says the team.
Of note, the positive association of these gene sets with schizophrenia was driven by small effects of all the genes in combination, rather than larger effects of just a few genes. This is in line with the theory that schizophrenia results from the combined effects of thousands of common alleles.
“Our results indicate that glial cells are key candidates contributing to the primary development of underlying pathological processes of schizophrenia, which may have important implications for its understanding and treatment,” conclude the researchers.
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Eleanor McDermid, Senior medwireNews Reporter