Associations between peripheral inflammation and clinical phenotypes of bipolar depression in a lower-middle income country

Objective: There has been increased interest in repurposing anti-inflammatories for the treatment of bipolar depression. Evidence from high-income countries suggests that these agents may work best for specific depressive symptoms in a subset of patients with biochemical evidence of inflammation but data from lower-middle income countries (LMICs) is scarce. This secondary analysis explored the relationship between pretreatment inflammatory markers and specific depressive symptoms, clinical measures, and demographic variables in participants with bipolar depression in Pakistan. Methods: The current study is a cross-sectional secondary analysis of a randomized controlled trial (RCT) of two anti-inflammatory medications (minocycline and celecoxib) for bipolar depression (n=266). A series of logistic and linear regression models were completed to assess the relationship between CRP (CRP> or < 3 mg/L and log10CRP) and clinical and demographic features of interest and symptoms of depression. Baseline clinical trial data was used to extract clinical and demographic features and symptoms of depression were assessed using the 24-item Hamilton Depression Rating Scale (HDRS-24). Results: The prevalence of low-grade inflammation (CRP>3 mg/L) in the sample was 70.9%. After adjusting for baseline body mass index (BMI), socioeconomic status (SES), age, gender, symptoms related to anhedonia, fatigue, and motor retardation were most associated with low-grade inflammation. Conclusion: BD patients from LMICs may experience higher rates of peripheral inflammation than have been reported in Western populations with BD. Future trials of repurposed anti-inflammatory agents that enrich for participants with these symptom profiles may inform the development of personalized treatment for bipolar depression in LMICs.