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Background: To establish whether major depressive disorder (MDD), suicidal behaviors and psychotic features contribute to glial alterations in the human prefrontal cortex.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. 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.Results: 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.Limitations: Sample volumes are relatively small.Conclusions: Different glial functions in MDD were related to specific brain area, suicide or psychotic features. [ABSTRACT FROM AUTHOR]

Suicide, psychotic features and gender influence the epidemiology and clinical prognosis of bipolar disorder (BD). Differences in glial function between the genders might contribute to these clinical variables. Here we studied expression of glial genes in human post-mortem prefrontal cortex of BD and control subjects in relation to suicide, psychotic features and sex. Real time PCR was used to detect transcriptional alterations of 16 glia-related genes in two brain areas, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), from 30 patients with BD subdivided by suicide and psychotic features, and from 34 well-matched control cases. We found no evidence of immune activation in BD. Instead, we found three microglial genes to be downregulated in the DLPFC of non-suicidal individuals with BD, i.e. CD68, triggering receptor expressed on myeloid cells 2 (TREM2) and purinergic receptor 12 (P2RY12). A remarkable sex difference was observed in the DLPFC of patients with BD: 14 glia-related genes were expressed at significantly higher levels in males, including all three glial cell types. A subset analysis showed that the sex differences were closely associated with the presence of psychotic features. No evidence of immune activation was found in these two brain regions in BD. The sex-specific differences in glial gene expression in BD, found particularly in patients with psychotic features, may be associated with the potential co-existence of mania and psychotic features and could potentially contribute to the gender-biased characteristics in BD. [ABSTRACT FROM AUTHOR]

Patients with schizophrenia (SCZ) run a lifelong risk of suicide. Alterations in glia activities in the prefrontal cortex (PFC) have been reported in relation to suicide in patients with SCZ. While immune processes in the CNS have been related to the susceptibility and course of SCZ, there are hardly any direct comparisons between individuals with SCZ, both those who died of natural causes and those that committed suicide, and healthy controls. We compared mRNA expression using real time qPCR of 16 glia-related genes in the dorsal lateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) between 35 patients with SCZ (7 suicide completers and 28 patients who died of natural causes) and 34 well-matched controls without psychiatric or neurological diseases. We found an increased expression of the astrocytic gene aldehyde dehydrogenase-1 family member L1 (ALDH1L1) mRNA, a marker involved in dopaminergic activity, in SCZ versus controls. Excluding individuals with SCZ that committed suicide resulted in an elevated expression in the DLPFC of both ALDH1L1 and glutamine synthetase (GS) genes in patients with SCZ, compared to suicide completers and non-psychiatric controls. Regarding microglia genes: in the ACC, homeostatic markers such as chemokine (C-X3-C motif) ligand 1 (CX3CR1) mRNA expression was increased in SCZ without suicide as compared to suicide completers, while no change was found when compared to controls. Another, purinergic receptor 12 (P2RY12) mRNA was exclusively elevated in the ACC of suicide completers, compared to either other group. Triggering receptor expressed on myeloid cells 2 (TREM2) expression, which maintains microglial metabolism, was reduced in non-suicide patients with SCZ, compared to suicide victims and control subjects. Differential changes are found in astrocyte and microglia genes in the PFC subregions in relation to SCZ and suicide, indicating possible disturbances of glia homeostasis in these conditions. [ABSTRACT FROM AUTHOR]