Changes in glial gene expression in the prefrontal cortex in relation to major depressive disorder, suicide and psychotic features

• Published in: Journal of affective disorders 2021-12, Vol.295, p.893-903
• Main Authors: Zhang, Lin, Verwer, Ronald W.H., Zhao, Juan, Huitinga, Inge, Lucassen, Paul J., Swaab, Dick F.
• Format: Article
• Language: English
• Subjects: Glia; Major depressive disorder; Prefrontal cortex; Psychotic features; Suicide
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2021.08.098

•Suicide and psychotic features confound glial expression in the PFC of MDD patients.•MDD is accompanied by dopaminergic and GABA activation, and strong demyelination.•Microglia phagocytosis was stronger in the DLPFC of suicide and psychotic features. To establish whether major depressive disorder (MDD), suicidal behaviors and psychotic features contribute to glial alterations in the human prefrontal cortex. We compared mRNA expression using real-time qPCR of 17 glia related genes in the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) between 24 patients with MDD and 12 well-matched controls without psychiatric or neurological diseases. The MDD group was subdivided into i) MDD who died of suicide (MDD-S) or natural causes (MDD-NS) and ii) MDD with or without psychotic features (MDD-P and MDD-NP). The results were followed up with confounder factor analysis. Astrocyte gene aldehyde dehydrogenase-1 L1 (ALDH1L1) showed an increased expression in the DLPFC of MDD-NS and the ACC of MDD-NP. S100 calcium-binding protein B (S100B) was upregulated in the DLPFC of MDD compared to the controls. Microglial markers CD11B and purinergic receptor 12 (P2RY12) both showed decreased expression in the ACC of MDD-NS. CD68 was increased in the DLPFC of MDD in both, MDD-S and MDD-P, compared to the controls. In addition, there was increased translocator protein (TSPO) expression in the DLPFC of MDD, especially MDD-NS. In the ACC, this gene had a lower expression in MDD-P than in MDD-NP. Myelin basic protein (MBP) mRNA in the DLPFC increased in MDD, in relation to psychotic features, but not to suicide. Sample volumes are relatively small. Different glial functions in MDD were related to specific brain area, suicide or psychotic features.