Brain Gene Expression Pattern of Subjects with Completed Suicide and Comorbid Substance Use Disorder

Abstract

Background/Aim: Although individuals with substance use disorder (SUD) are at high risk of committing suicide, most studies of postmortem gene expression exclude subjects with SUD due to the potential confounding effect of drugs in the transcriptome. Thus, little is known about the gene expression profile in suicides with SUD. The identification of altered biological processes in suicides with SUD is crucial in the comprehension of the interaction between both pathologies. Methods: We evaluated the gene expression profile in the dorsolateral prefrontal area of suicides and nonsuicides with and without SUD by microarrays. Results: We identified 222 differentially expressed genes, predominately enriched in cell proliferation in the comparison between suicides with and without SUD. When comparing the transcriptome of suicides with SUD to nonsuicides with SUD, we identified 550 differentially expressed genes, mainly enriched in oxidative phosphorylation. Differentially expressed genes (1,417) between suicides and nonsuicides without SUD were detected. Most of them were related to mitochondrial function. Conclusion: Interaction between suicide and SUD seems to influence the expression of genes involved in glial proliferation and glutamatergic neurotransmission. These results highlight, for the first time, that suicides with SUD have a gene expression profile distinct from that of subjects with only one of these disorders.

Reduced ribosomal DNA transcription in the prefrontal cortex of suicide victims: consistence of new molecular RT-qPCR findings with previous morphometric data from AgNOR-stained pyramidal neurons

“…in the process closely related to rDNA activity [9][10][11]. Correspondingly, different expression of genes related to the formation of neuronal processes has been observed in the PFC of male compared to female suicide completers [42,43]. However, the small sample size of female subjects may lead to an underpowered analysis and there is a chance of false negative results.…”

Fetal Megalencephaly with Cortical Dysplasia at 18 Gestational Weeks Related to Paternal UPD Mosaicism with PTEN Mutation

“…Hemimegaloencephaly with pachygyria [ 22 ] and focal cortical dysplasia with abnormal sulcation [ 23 ] were observed in patients with PTEN mutations. The incidence of cortical dysplasia in humans suggests that the PTEN gene is involved in neuronal migration [ 24 ]. Prominent multifocal cortical dysplasia was present in our case at 18–20 weeks of gestation.…”

“…On the contrary, if we assume that all cells are homozygous, early fetal demise may occur in early pregnancy. It was reported that mice with homozygous PTEN loss died before embryonic day 7.5, since the tissue could not appropriately differentiate into three germ layers of endoderm, mesoderm, and ectoderm, while mice with the heterozygous mutated PTEN allele were viable and showed neuronal proliferation during brain development [ 24 , 29 ].…”

Brain Gene Expression-DNA Methylation Correlation in Suicide Completers: Preliminary Results

“…The present study was approved by the Ethical Committee for Human Research at the National Institute of Genomic Medicine and the Bioethics Committee of the Faculty of Medicine at the National Autonomous University of Mexico (UNAM). Tissue samples from the dorsolateral prefrontal cortex (Brodmann area 9) were sectioned during an autopsy protocol, following a previously described procedure 30 . Samples were stored in RNAlater at -80°C until their use.…”