Serotonergic agents impact brain plasticity and reverse stress-induced dendritic atrophy in prime fronto-limbic brain areas associated with learning and memory.

The present study investigated the effects of the antidepressant escitalopram on the gray matter during relearning in healthy individuals to inform a model for depression and the neurobiological recovery processes.

It subjected 76 (44 females) healthy individuals to carry out daily associative learning tasks with emotional or non-emotional content over a 3-week period, which was followed by a 3-week relearning period (randomly shuffled association within the content group) with concurrent daily selective serotonin reuptake inhibitor (escitalopram 10mg) or placebo intake.

Using voxel-based morphometry in individuals who developed sufficient escitalopram blood levels over the 21-day relearning period, the study found an increased density of the left dorsolateral prefrontal cortex. On investigating an interaction between relearning and drug intervention for all participants, regardless of escitalopram levels, it detected no changes in gray matter with either surfaced-based or voxel-based morphometry analyses.

The left dorsolateral prefrontal cortex influences executive function and emotional processing and is a vital mediator of symptoms and treatment outcomes of depression. Accordingly, this study indicates that escitalopram facilitates neuroplastic processes in this region if blood levels are sufficient. 

However, it did not find an effect of escitalopram on brain structure that is dependent on relearning content, which might be a consequence of the intensity and duration of the interventions.

Vanicek T, Reed MB, Seiger R, et al. Increased left dorsolateral prefrontal cortex density following escitalopram intake during relearning: a randomized, placebo-controlled trial in healthy humans. Therapeutic Advances in Psychopharmacology. 2022;12. doi:10.1177/20451253221132085