Escitalopram Administration, Neuroplastic Effects and Relearning: A Diffusion Tensor Imaging Study in Healthy Individuals

Background: Neuroplastic processes are influenced by selective serotonergic reuptake inhibitors, while learning in conjunction with the administration of serotonergic agents alters white matter microstructure in humans. The goal of this double-blind, placebo-controlled imaging study was to investigate the influence of escitalopram on white matter plasticity during (re)learning. Methods: Seventy-one healthy individuals (age = 25.6+/-5.0, 43 females) underwent 3 diffusion magnetic resonance imaging sessions: at baseline, after 3-weeks of associative learning (emotional/non-emotional content) and after relearning shuffled associations for an additional 3 weeks. During the relearning phase, subjects received daily escitalopram 10 mg or placebo orally. Data were analyzed using the FMRIB Software Library (FSL) and the implemented Tract-Based Spatial Statistics (TBSS) approach. Results: The TBSS analysis revealed widespread decreases in fractional anisotropy metrics in subjects that received escitalopram. In addition, axial diffusivity decreases were mainly found in the corpus callosum and in areas within the internal capsule. In subjects receiving placebo, we did not find such effects, nor did our results show diffusivity changes related to learning or relearning. Conclusion: Diffusivity changes were found within several tracts in the escitalopram group, while we observed no changes in the placebo group. Although previous studies examining the effects of SSRIs on white matter tracts in humans are underrepresented, our results suggest a relationship between serotonergic agents and diffusivity parameters. The findings of this study implicate that escitalopram may directly or indirectly impact white matter microstructures in healthy subjects. Nevertheless, we did not find a relationship between serotonergic modulation, neuroplastic effects and relearning.