Serum biomarkers, lifetime substance use and conversion to bipolar disorder.

Introduction: The diagnostic conversion of major depressive disorder (MDD) to bipolar disorder (BD) is a topic that is currently the subject of several studies. However, there are few studies that clarify the interaction between conversion, substance use and biomarkers.

Objectives: The aim of this study was to investigate serum biomarker levels and lifetime substance use as predictors for diagnostic conversion from major depressive disorder to bipolar disorder in an outpatient sample of adults.

Methods: This was a prospective longitudinal study nested within a larger two-phase study. Male and female individuals, between the ages of 18 and 60, diagnosed with MDD by the Mini International Neuropsychiatric Interview Plus who participated in the two stages of the study were included. The instrument alcohol smoking and substance involvement screening test (ASSIST) was used to evaluate substance use. The enzyme linked immuno sorbent assay (ELISA) technique was used to measure the levels of the following biomarkers: brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α).

Results: The conversion rate from MDD to BD was 12.4%. The prevalence of female individuals, subjects with up to eight years of schooling, who had lifetime psychotic symptoms and reported lifetime use of cocaine was higher among individuals who converted their diagnosis to BD than among individuals who did not (P<0.05). In the crude analysis, there was no interaction between biomarkers and substance use except for NGF with cocaine. Based on the adjusted analysis model, it was observed that the interaction remains (OR: 1.476; 95% CI: 1.019-2.137).

Conclusions: Individuals with late diagnosis and treatment of bipolar disorder may have a worse prognosis. Therefore, results suggesting that NGF and cocaine use are potential predictors of conversion to bipolar disorder can help in clinical practice, contributing to the identification of conversion and to more specific therapeutic interventions.