Study supports role of the immune system in depression

Reuters Health - 01/11/2021  - Genes that increase a person's susceptibility to depression are also associated with increased white blood cell (WBC) count - and this association may be bidirectional, according to a genetic association study by researchers with the PsycheMERGE Network.

While the underlying biological basis for depression remains poorly understood, depression is consistently associated with increased proinflammatory biomarkers. However, the mechanisms underlying these associations remain unclear, the researchers explain in JAMA Psychiatry.

Dr. Lea Davis of Vanderbilt Genetics Institute, in Nashville, Tennessee, and colleagues leveraged data from four healthcare systems participating in the PsycheMERGE Network to examine the association between depression polygenic risk scores (PGS) and a variety of clinical laboratory values.

They found a significant association between depression PGS and increased WBC count that was "robustly replicated" across the four independent biobanks.

Increased polygenic depression risk was associated with increased WBC count "even after controlling for depression, anxiety, multiple comorbid phenotypes, body mass index, and smoking, thus suggesting that depression PGS was an important risk factor for the proinflammatory state observed in depression," the researchers report.

"The association of the depression PGS with WBC was modest across all biobanks, suggesting that individuals with high depression genetic liability may have an activated but not abnormal immune system. Nonetheless, sustained activation of the immune system could have important implications for the risk of developing depression," they note in their paper.

Mediation analyses suggested a bidirectional association between WBC count and depression and implicated neutrophils as driving the association.

Mendelian randomization results supported a potential causal path from increased WBC levels to increased depression risk, consistent with the neuroinflammation model which hypothesizes that an activated immune system contributes to risk of developing depression. However, this analysis did not support a model of depression leading to increased WBC levels.

"The associations described in this study highlight the importance of WBC biology in depression and demonstrate the potential use of (electronic health record)-based genomics as a tool for discovery of physiological markers in psychiatric traits," the authors conclude.

This research had no commercial funding.

SOURCE: https://bit.ly/2Z95dyl JAMA Psychiatry, online October 20, 2021.

By Reuters Staff



Posted on 1 November, 20219 November, 2021