Serum brain-derived neurotrophic factor levels in relation to comorbid depression and cytokine levels in Nepalese men with alcohol-use disorders

Abstract

Neurodegenerative and inflammatory processes are involved separately in major depression (MD) and alcohol-use disorders (AUD). Little is known about the nature of this relationship in the context of comorbid AUD and depression disorders. In this study, we determined brain-derived neurotrophic factor (BDNF) serum levels in patients with AUD and tested whether BDNF levels were related to history of major depression, recent depressive symptoms, AUD severity, and TNF-α and IL-6 levels. Nepalese male AUD inpatients (N=152) abstinent from alcohol for an average of 34 days were administered structured interviews to assess depression symptoms and pattern and extent of alcohol use, and to generate research diagnoses for AUD and MD. AUD severity was assessed by scores on the Alcohol Use Disorder Identification Test. Serum BDNF and cytokines were measured using ELISA and multiplex technology, respectively. Although serum BDNF levels were unrelated to MD history, patients with recent depressive symptoms (n=42) had lower (mean±SD) BDNF serum levels compared to those without (n=110) (21.6±8.1 ng/mL vs. 26.0±9.6 ng/mL; p=0.010), and patients with higher AUD severity and binge-drinking patterns had higher mean serum BDNF levels compared to lower AUD severity and non-binging (25.9±9.7 ng/mL vs. 22.1±8.7 ng/mL; p=0.022 and 25.7±9.3 vs. 21.8±9.7 ng/mL; p=0.029, respectively). Positive correlations were present between BDNF and TNF-α (r=0.39, p<0.001) and IL-6 (r=0.2, p=0.027). In particular, TNF-α levels were predictive of BDNF levels after controlling for confounders (B=0.3 [95% CI=0.2-0.5], p<0.001). These findings show that in alcohol-using populations, peripheral BDNF levels are related to severity of AUD as well as presence of depressive symptoms. The significant associations between inflammatory and neurotrophic factors may have implications for neuroadaptive changes during recovery from AUD.

Keywords: Alcohol-use disorder; Brain-derived neurotrophic factor; Depression; Interleukin-6; Tumor necrosis factor.