Abstract
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.
Competing Interest Statement
There are no conflicts of interest to declare regarding the present study. R. Lanzenberger received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR and Heel and has served as a consultant for Ono Pharmaceutical. He received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. C. Kraus received travel grants from Roche and AOP Orphan Austria, speaker honoraria from Janssen. D. Winkler received lecture fees/authorship honoraria within the last three years from Angelini, Lundbeck, MedMedia Verlag, and Medical Dialogue.