Enhancement of Learning Associated Neural Plasticity by Selective Serotonin Reuptake Inhibitors

Summary

Background:

Conclusive evidence states that the serotonergic system mediates neuroplasticity from early embryonic development until brain maturation in adulthood. This study aims to demonstrate that selective serotonin reuptake inhibitors (SSRIs) enhance learning-dependent neuroplasticity in vivo, hereby contributing to the investigators understanding of the mechanism of action of therapy with SSRIs.

Objectives:

1. To prove a positive influence of SSRIs on structural remodeling during learning, reflected by enhancements of gray and white matter microstructure, connectivity and functionality in brain regions involved in learning processes.
2. To show that this effect is topologically specific, i.e. that enhancements of plasticity markers are found in different regions depending on their involvement during the performance of specific learning tasks.

Study design:

Randomized, double-blind, placebo-controlled, longitudinal mono-center study. 80 healthy subjects will undergo three MRI scanning sessions: 1. baseline, at study entry, 2. after 3 weeks of facial/emotional (n=40) or Chinese character-meaning learning (n=40) and 3. after 3 weeks learning of new associations under administration of an SSRI or placebo.

Methods:

MRI measurements will be performed on a 3 Tesla PRISMA MAGNETOM MR scanner. Changes in gray matter microstructure will be assessed using high-resolution structural MRI and analyzed with voxel-based morphometry (VBM). Diffusion tensor imaging (DTI) enables non-invasive investigation of neuroplasticity in the human brain based on the reduction in mean diffusivity associated with swelling of astrocytes after increased synaptic activity. Resting-state functional MRI (fMRI) will allow for the measurement of changes in functional coupling between brain regions, and fMRI during tasks will assess differential activity in brain regions during learning.

Relevance and implications:

This study aims to provide evidence that SSRIs facilitate cytoarchitectonical restructuring. In addition to expanding the investigators current knowledge on the trophic effects of SSRIs, the results of this study will also elucidate interactions between the serotonergic system and changes to neuronal networks during learning as well as their behavioral consequences. By probing the neurobiological correlates of the antidepressant and anti-anxiety effects of SSRIs, this study will provide a rationale for targeted interventions that harness the neuroplasticity enhancing properties of SSRIs to facilitate therapeutic processes.

Conditions

• Ssri
• Neuronal Plasticity

Interventions

DRUG

Escitalopram

Tablet 10mg, 21 days

DRUG

Placebo

Tablet, 21 days

OTHER

3xMR scan (fMRI, DTI, strucutral MRI)

3 Tesla PRISMA MAGNETOM MR scanner; performed at baseline, after 21 days of performing learning paradigms and after 21 days of drug/placebo treatment and re-learning paradigms

BEHAVIORAL

Association learning paradigm

21 daily internet-based sessions (20min) of learning associations (pairs) of stimuli

BEHAVIORAL

Association re-learning paradigm

21 daily internet-based sessions (20min) of learning new associations (pairs) of stimuli performed during escitalopram/placebo treatment

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-08-31

Primary Completion

2019-08-31

Countries

• Austria

Study Locations