Translational Psychiatry (Feb 2024)

Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder

  • Nicolas A. Nuñez,
  • Brandon J. Coombes,
  • Lindsay Melhuish Beaupre,
  • Aysegul Ozerdem,
  • Manuel Gardea Resendez,
  • Francisco Romo-Nava,
  • David J. Bond,
  • Marin Veldic,
  • Balwinder Singh,
  • Katherine M. Moore,
  • Hannah K. Betcher,
  • Simon Kung,
  • Miguel L. Prieto,
  • Manuel Fuentes,
  • Mete Ercis,
  • Alessandro Miola,
  • Jorge A. Sanchez Ruiz,
  • Gregory Jenkins,
  • Anthony Batzler,
  • Jonathan G. Leung,
  • Alfredo Cuellar-Barboza,
  • Susannah J. Tye,
  • Susan L. McElroy,
  • Joanna M. Biernacka,
  • Mark A. Frye

DOI
https://doi.org/10.1038/s41398-024-02798-y
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 5

Abstract

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Abstract There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.