Despite a broad understanding of depression as a psychiatric disorder, the underlying biological effects of depression are still poorly understood. A new study suggests that increased polygenic scores for depression are associated with increased white blood cell counts, which highlights the importance of the immune system in the etiology of depression.

They also found that even having a high genetic risk for depression was enough to contribute to an elevated white blood cell count.

The primary analyzes for the study were performed on the VUMC biobank, and replication analyzes were performed on the other three healthcare systems. The results of the electronic medical record data of 382,452 patients were meta-analyzed in the four systems.


The researchers’ results show a feedback loop in which people who are at a higher genetic risk for depression also have a higher initial level of inflammation. If a person develops depression, that increases inflammation-related biomarkers even more. Their findings also suggest that the association between polygenic depression scores and increased white blood cell count is bidirectional..

Julia Sealock, a graduate student in Human Genetics and first author of the paper, hopes that the results will motivate the future development of clinical biomarkers and specific treatment options for depression:

I believe that our research contributes to increasing the evidence for a pro-inflammatory state in depression and creates an exciting opportunity to think about a new class of antidepressant therapies focused on reducing pro-inflammatory markers. Now we can start to wonder if the reduction in pro-inflammatory markers leads to an antidepressant effect. If so, this could cause a paradigm shift in depression treatment from focusing on changing brain chemistry to changing biomarkers on the periphery.