Understanding Suicide: Neuroinflammation and Epigenetic Regulation in the Brain

2023-11-17 06:28:00

American researchers have found that in the brains of people who died by suicide, the expression and positive epigenetic regulation of genes associated with inflammation are increased compared to those who died from other causes. Publication about this appeared In the magazine Molecular Psychiatry. Lena Brundin of the Van Andel Institute and colleagues analyzed transcriptomes and DNA methylation profiles in pole temporal lobe brain samples from 29 suicide victims and 32 otherwise comparable people who died suddenly from accidents, homicides, or myocardial infarction. During interviews with their loved ones using various diagnostic scales and questionnaires, all participants from the main group were diagnosed with major depressive disorder, one of them also suffered from obsessive-compulsive disorder. No psychopathology was detected in the control group. Participants in both groups were not taking antidepressants or antipsychotic medications, and their toxicology test results were not significantly different.

The analysis showed that gene expression was significantly reduced in the brains of those killed by suicide. NPAS4 – one of the key transcriptional regulators of neuroinflammation, neuroprotection and neuroplasticity, as well as mitochondrial MTRNR1, taking part in metabolic homeostasis. They also identified 40 differentially methylated genomic regions related to seven genes that are responsible for inflammation and the immune response (ARPC2, CX3CL1, PSMB2, RNF41, RSF1, SPN and USP14they were activated), and four more involved in neurodevelopment and transmission of nerve impulses (GRIK2, NDRG4, PRARD and ZNF24, they were depressed). Deconvolution analysis also showed that in the brains of those who committed suicide, the number of oligodendrocytes, cells responsible for the myelination of nerve fibers and protecting them from oxidative stress, was reduced. The key regulator of all these processes is highly likely to be NPAS4, which deserves further study as a potential biomarker of suicidal behavior and a target for therapy.