Potential Inflammatory Biomarkers for Major Depressive Disorder Related to Suicidal Behaviors: A Systematic Review

Abstract

Major depressive disorder (MDD) is a highly prevalent psychiatric condition affecting an estimated 280 million individuals globally. Despite the occurrence of suicidal behaviors across various psychiatric conditions, MDD is distinctly associated with the highest risk of suicide attempts and death within this population. In this study, we focused on MDD to identify potential inflammatory biomarkers associated with suicidal risk, given the relationship between depressive states and suicidal ideation. Articles published before June 2023 were searched in PubMed, Embase, Web of Science, and the Cochrane Library to identify all relevant studies reporting blood inflammatory biomarkers in patients with MDD with suicide-related behaviors. Of 571 articles, 24 were included in this study. Overall, 43 significant biomarkers associated with MDD and suicide-related behaviors were identified. Our study provided compelling evidence of significant alterations in peripheral inflammatory factors in MDD patients with suicide-related behaviors, demonstrating the potential roles of interleukin (IL)-1β, IL-6, C-reactive protein, C-C motif chemokine ligand 2, and tumor necrosis factor-α as biomarkers. These findings underscore the intricate relationship between the inflammatory processes of these biomarkers and their interactions in MDD with suicidal risk.

Molecular Changes Associated with Suicide

“…The increased risk of suicidality in patients with MDD has been associated with inflammatory changes such as lowered BDNF or increased interleukin 1ß (IL-1ß), interleukin-6 (IL-6), interleukin-13 (IL-13), tumor necrosis factor α (TNF-α), C reactive protein (CRP) and C-C motif chemokine ligand 2 (CCL2), dysfunctions of the HPA-axis, with overproduction of CRH and elevated glucocorticoid production, and structural and functional brain changes [36,41,42] (Figure 1). Recent GWAS analyses have shown that genetic liability for MDD increases the risk for suicide attempts, as suicide-attempters with MDD, BD, and schizophrenia had higher polygenic risk scores for MDD than non-attempters [33].…”