Systematic review: The role of complete blood count components as diagnostic biomarkers in major depressive disorder

Background: Major depressive disorder (MDD) remains challenging to diagnose due to reliance on subjective clinical assessments, sparking interest in objective biological markers. Complete blood count (CBC) parameters reflect underlying biological processes, such as inflammation and oxygen transport dysfunction, both of which are implicated in MDD pathophysiology. Objectives: The purpose of this systematic review is to explore the potential role of CBC parameters as biomarkers for diagnosing and assessing the severity of MDD. Data Sources: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, analyzing studies published between 2014 and 2024. Databases searched included PubMed, CINAHL Complete, Scopus, PsycINFO, and Web of Science. A total of 22 studies met the inclusion criteria. Conclusions: The majority of studies (approximately 17 out of 22) found that low red blood cell indices and elevated neutrophil-to-lymphocyte ratio were associated with symptoms such as fatigue, cognitive impairment, and chronic inflammation. Although individual CBC parameters showed moderate diagnostic utility, composite CBC scores demonstrated promise in identifying patients with higher MDD severity. However, only a small number of longitudinal studies (5 of 22) examined CBC changes over time or in response to treatment, and findings were mixed. Therefore, although CBC parameters show potential for clinical integration, their predictive value for treatment outcomes remains inconclusive and warrants further investigation. Implications for Practice: Standardizing CBC biomarker thresholds and further exploring the role of inflammation in MDD are essential for clinical integration. Complete blood count biomarkers hold promise for enhancing early detection and enabling personalized treatment approaches in primary care and psychiatric settings.