Abstract

BackgroundTo establish whether major depressive disorder (MDD), suicidal behaviors and psychotic features contribute to glial alterations in the human prefrontal cortex. Materials and methodsWe 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. ResultsAstrocyte 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. LimitationsSample volumes are relatively small. ConclusionsDifferent glial functions in MDD were related to specific brain area, suicide or psychotic features.

Highlights

  • One-third of individuals with major depressive disorder (MDD) attempt suicide during their lifetime (Dong et al, 2019)

  • As an indication for changes in astrocyte-related functions in the prefrontal cortex (PFC) of patients with MDD, we analyzed qPCR values of three gene tran­ scripts: aldehyde dehydrogenase 1 family, member L1 (ALDH1L1), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B)

  • To assess whether MDD, suicide and psychotic features may be accompanied by gene expression changes of proteins characteristic for microglia, we tested the expression levels of the following 10 microglial markers

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Summary

Introduction

One-third of individuals with major depressive disorder (MDD) attempt suicide during their lifetime (Dong et al, 2019). Glial-driven functional brain changes have been explored in MDD pathophysiology, and several suicide-/psychotic features-related specific glial alterations have been described in bipolar disorder and schizophrenia (SCZ) (Zhang et al, 2020a,2020b). Within this frame­ work, the pathological studies on the two regions that reported glial abnormalities required some follow up. Materials and methods: 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. Conclusions: Different glial functions in MDD were related to specific brain area, suicide or psychotic features

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