The Potential of Polygenic Risk Scores to Predict Antidepressant Treatment Response in Major Depression: A Systematic Review

J Affect Disord. 2022 May 1:304:1-11. doi: 10.1016/j.jad.2022.02.015. Epub 2022 Feb 11.

Abstract

Background: Understanding the genetic underpinnings of antidepressant treatment response in unipolar major depressive disorder (MDD) can be useful in identifying patients at risk for poor treatment response or treatment resistant depression. A polygenic risk score (PRS) is a useful tool to explore genetic liability of a complex trait such as antidepressant treatment response. Here, we review studies that use PRSs to examine genetic overlap between any trait and antidepressant treatment response in unipolar MDD.

Methods: A systematic search of literature was conducted in PubMed, Embase, and PsycINFO. Our search included studies examining associations between PRSs of psychiatric as well as non-psychiatric traits and antidepressant treatment response in patients with unipolar MDD. A quality assessment of the included studies was performed.

Results: In total, eleven articles were included which contained PRSs for 30 traits. Studies varied in sample size and endpoints used for antidepressant treatment response. Overall, PRSs for attention-deficit hyperactivity disorder, the personality trait openness, coronary artery disease, obesity, and stroke have been associated with antidepressant treatment response in patients with unipolar MDD.

Limitations: The endpoints used by included studies differed significantly, therefore it was not possible to perform a meta-analysis.

Conclusions: Associations between a PRS and antidepressant treatment response have been reported for a number of traits in patients with unipolar MDD. PRSs could be informative to predict antidepressant treatment response in this population, given advances in the field. Most importantly, there is a need for larger study cohorts and the use of standardized outcome measures.

Keywords: Antidepressant treatment response; Antidepressants; Major depressive disorder; Pharmacogenetics; Polygenic risk score.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Depression
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / epidemiology
  • Depressive Disorder, Major* / genetics
  • Humans
  • Multifactorial Inheritance
  • Risk Factors

Substances

  • Antidepressive Agents