Baseline Plasma BDNF Levelsare Associated with Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Major Depressive Disorder

Objective: Evidence has shown that brain-derived neurotrophic factor (BDNF) is associated with anhedonia symptoms in major depressive disorder (MDD) patients, while the rapid antianhedonic effects of ketamine may occur independently of depressive symptoms. To our knowledge, the relationship between plasma BDNF (pBDNF) and the effect of repeated-dose intravenous ketamine on anhedonic symptoms has not been investigated. Methods: Seventy-five Chinese individuals with MDD received ketamine treatments. Anhedonia and pBDNF concentrations were evaluated with a subscale of the Montgomery-Åsberg Depression Rating Scale (MADRS) and enzyme-linked immunosorbent assay (ELISA) at baseline, day 13 and day 26. Results: Baseline pBDNF levels were associated with changes in anhedonic symptoms on day 13 (r=0.30, P=0.008). Interestingly, pBDNF concentrations were associated with changes in anhedonia symptomson day 26 (r= -0.32, P=0.02). Baseline pBDNF levels were higher in antianhedonic responders than in antianhedonic nonresponders (F=4.2, P=0.04). Ketaminereduced anhedonia symptoms in antianhedonic responders compared to nonresponders on days 13 and 26 (all Ps<0.05). The baseline high BDNF group had a lower level of anhedonia than the low BDNF group on days 13 (P<0.001) and 26 (P=0.01). Conclusion: Our study suggests that baseline pBDNF concentrations may predict the antianhedonic effect in individuals with MDD treated with repeated doses of ketamine. Clinicl Trial Registration Number: ChiCTR-OOC-17012239.