Distinct Gene Expression Signature Identified in Group of Patients With MDD

Patients with major depressive disorder (MDD) who died by suicide had a gene expression signature distinct from other patients with MDD that included genes involved in stress response and polyamine metabolism, immune response, and telomere maintenance, according to a study published online in Translational Psychiatry. 

“Genes identified as dysregulated in suicide could be potential targets for future pharmacological interventions to prevent suicide in MDD patients but could also be used to develop a molecular test to identify patients at high risk for suicide,” wrote corresponding author Adolfo Sequeira, PhD, of the University of California, Irvine, School of Medicine, and coauthors.

The study included postmortem blood and brain samples from a total 45 subjects, including patients with MDD who died by suicide, patients with MDD who died by means other than suicide, and nonpsychiatric control subjects. Researchers analyzed gene expression in the samples using a novel approach less sensitive to the effects of RNA degradation.

The analysis identified 14 genes in the blood that significantly differentiated patients with major depressive disorder who died by suicide from patients with MDD who died by other means. The top six genes differentially expressed in blood were PER3, MTPAP, SLC25A26, CD19, SOX9, and GAR1, according to the study.

Related: Inflammation Connected to Risk of Major Depressive Disorder

Four genes showed significant changes in both brain and blood samples in patients with MDD who died by suicide: SOX9 was decreased and PER3 was increased in both tissues, while CD19 and TERF1 were increased in blood but decreased in the brain’s dorsolateral prefrontal cortex (DLPFC).

“Our study design, which includes age- and gender-matched comparison groups, allowed for the identification of suicide-specific expression changes either unique to or in common between DLPFC and blood,” researchers wrote. “Specifically, stress response changes, including polyamine metabolism, circadian rhythm, immune dysregulation, and telomere maintenance are shared among suicides in blood, suggesting future studies in large clinical populations investigating these systems might help in the identification of acutely suicidal MDD patients.”

References

Mamdani F, Weber MD, Bunney B, et al. Identification of potential blood biomarkers associated with suicide in major depressive disorder. Transl Psychiatry. Published online April 14, 2022. doi: 10.1038/s41398-022-01918-w

UCI researchers reveal possible molecular blood signature for suicide in major depression. News release. University of California, Irvine; May 5, 2022. Accessed June 17, 2022.