Antidepressants are associated with decreased white blood cell counts beyond the effect of statins in individuals with co-morbid depression and coronary artery disease: A longitudinal analysis in the Vanderbilt University Medical Center and All of Us cohorts

Depression and coronary artery disease (CAD) are comorbid, prevalent conditions responsible for significant morbidity and mortality. Understanding the co-occurrence of these conditions can facilitate early diagnosis and treatment recommendations. Routinely prescribed treatments are available for both CAD and depression, and interactions between serotonin signaling, the immune system, and cardiovascular system suggest cross-treatment of CAD and depression may be indicated. In this study we use repeated, longitudinal WBC count measures from over one million participants in the Vanderbilt University Medical Center (VUMC) electronic health records (EHR) to characterize changes in systemic inflammation in response to CAD and depression diagnoses and their respective treatments. After controlling for potential confounders, individuals with comorbid depression-CAD have higher median WBC counts than controls and individuals with depression only but not higher than individuals with CAD only. In our longitudinal modeling cohort of individuals with both depression and CAD, there was a significant decrease in WBC count after statin initiation and after anti-depressant initiation. Additionally, initiating antidepressants after statins was associated with a further decrease in WBC count, however the reverse was not true. This work highlights the continued importance and necessity of evaluating the immunomodulatory effects of depression and CAD and their respective treatments in individuals with both depression and CAD.