Changes in RNA expression levels during antidepressant treatment: a systematic review

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• Treatment resistance is a significant challenge in antidepressant therapy, affecting over a third of patients.
• The precise molecular mechanisms underlying antidepressant efficacy remain incompletely understood.

Purpose of the Study:

• To systematically review clinical studies investigating RNA expression changes following antidepressant treatment.
• To identify potential RNA-based biomarkers associated with antidepressant response.

Main Methods:

• A systematic literature search adhering to PRISMA guidelines was conducted up to April 2021.
• Thirty-one peer-reviewed studies measuring mRNA or non-coding RNA levels before and after antidepressant treatment in humans were included.
• Qualitative synthesis was employed due to significant heterogeneity in study designs and measured RNAs.

Main Results:

• Significant heterogeneity was observed across studies regarding measured genes/RNAs, antidepressant types, and treatment durations.
• Consistent alterations in the expression of brain-derived neurotrophic factor (BDNF) and inflammation-related genes, notably IL-1β, were reported across multiple studies.
• Six specific RNAs were examined by more than one study, with BDNF and inflammatory genes showing consistent changes.

Conclusions:

• Genes within the BDNF and inflammatory pathways are consistently altered by antidepressant treatment, indicating their potential as therapeutic targets.
• The findings underscore the need for robust, placebo-controlled studies to validate these RNA expression changes as reliable markers for improving antidepressant treatment outcomes.