Higher white blood cell count tied to genetic depression risk

Increased white blood cell count appeared linked to increased depression polygenic scores, with a potential bidirectional association, according to results of a genetic association study published in JAMA Psychiatry.

“We’ve known for a while now that there is a link between depression and inflammation, but what we didn’t know was whether inflammation led to depression or depression led to inflammation,” Lea K. Davis, PhD, of the division of genetic medicine at Vanderbilt University in Tennessee, told Healio Psychiatry. “In this study, we used electronic health records linked to genetic data at four different institutions to ask whether there is an increase in inflammatory biomarkers in people who have high genetic risk for depression but who don’t have clinical depression.”

Davis and colleagues conducted the study between May 19, 2019, and June 5, 2021, analyzing EHR data from 382,452 participants (18.7% female; median age, 57.9 years) of European ancestry. They conducted separate analyses in each health care system and a meta-analysis across all systems, with primary analyses in Vanderbilt University Medical Center’s biobank. Replication analyses occurred at Icahn School of Medicine at Mount Sinai, Massachusetts General Brigham and the Million Veteran Program.

The researchers included all participants with available genetic data and recorded measurements of white blood cell count. They conducted primary analyses among people of European descent and repeated these among a population of people of African descent (n = 12,383; 61.1% female; median age, 39 years). Depression polygenic scores served as the exposure and white blood cell count as the main outcome.

Results of a laboratory-wide association scan showed a significant association between depression scores and white blood cell count. The researchers replicated this association in the meta-analysis. They noted a bidirectional association suggested by mediation analyses, with white blood cell count having accounted for 2.5% of the association of depression polygenic score with depression diagnosis. Moreover, depression diagnosis accounted for 9.8% of the association of depression polygenic score with white blood cell count. Davis and colleagues reported additional support in Mendelian randomization for the association between increased white blood cell count and depression risk; however, depression modeled as the exposure revealed no evidence of white blood cell counts having an effect.

“There are no recommended changes to diagnosis or treatment of depression based on this study; however, this study does motivate further research to better understand the anti-inflammatory effect of antidepressants,” Davis said. “Additionally, it raises the hypothesis that anti-inflammatory drugs or foods might be helpful in preventing depression. Both of these areas deserve additional large-scale rigorous research before clinical recommendations can be made.”