Abstract Background The brain-derived neurotrophic factor (BDNF) has been implicated in processes essential for neuroplasticity. Learning and serotonin reuptake inhibitors (SSRI) foster neuronal reorganization, a mechanism potentially related to BDNF. This study aims to assess the effects of associative learning and escitalopram on serum BDNF (sBDNF) levels, to gain further knowledge on their dynamic interplay. Methods For three weeks, 37 participants performed one of two associative learning paradigms with either emotional or semantic content daily. During a subsequent three-week period of reversal learning, subjects either received escitalopram (10mg per day) or placebo. Before and after each learning period sBDNF values were assessed. Citalopram plasma levels were measured at the last time point. Linear mixed effects models (LME) and partial Spearman’s rank and Pearson correlations were used for statistical analyses. Results One-way LME resulted in a significant effect of time during the first learning period over both groups (p&lt;0.01). Two-way LME revealed a significant interaction effect of the emotional content learning group and time (p=0.02). Three-way LME (time x reversal learning group x substance) showed no significant effects (all p&gt; 0.05). Furthermore, correlation between citalopram and sBDNF level after three weeks of escitalopram administration exhibit a negative trend (partial Pearson correlation: r=-0.30, p=0.05; partial Spearman’s rank: r=-0.22, p=0.15). Conclusion The results suggest that three weeks of associative emotional content learning affect sBDNF levels, while subsequently assessed citalopram plasma and sBDNF levels tend to correlate negatively. Key Points Emotional learning may affect serum BDNF levels in healthy human subjects Blood levels of citalopram and serum BDNF exhibit a negative correlation

Effects of learning and escitalopram administration on serum BDNF levels, a randomised placebo-controlled trial