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

TY - JOUR

T1 - Changes in glial gene expression in the prefrontal cortex in relation to major depressive disorder, suicide and psychotic features

AU - Zhang, Lin

AU - Verwer, Ronald W.H.

AU - Zhao, Juan

AU - Huitinga, Inge

AU - Lucassen, Paul J.

AU - Swaab, Dick F.

N1 - Funding Information: This research was supported by the ‘Stichting Vrienden van het Herseninstituut’. Funding Information: Postmortem brain samples were obtained from the Stanley Medical Research Institute (Director: Dr. Maree J Webster) Depression Collection. We thank Arja Sluiter and Dr. Yuting Hu for their technical support. Publisher Copyright: © 2021

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

KW - Glia

KW - Major depressive disorder

KW - Prefrontal cortex

KW - Psychotic features

KW - Suicide

UR - http://www.scopus.com/inward/record.url?scp=85114720826&partnerID=8YFLogxK

U2 - 10.1016/j.jad.2021.08.098

DO - 10.1016/j.jad.2021.08.098

M3 - Article

AN - SCOPUS:85114720826

SN - 0165-0327

VL - 295

SP - 893

EP - 903

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -