Genetic Variants Associated With Treatment Response in Bipolar Disorder: A Systematic Review

To identify genetic variants associated with pharmacological treatment response in individuals with bipolar disorder (BD).

A systematic review was conducted by searching PubMed, Scopus, PsycINFO, SciELO, and LILACS from inception through January 2025. Eligible studies examined associations between genetic variants and pharmacological treatment response in BD. Study selection, eligibility assessment, and methodological quality assessment were independently performed by 2 reviewers. Extracted data included publication year, study design, setting, eligibility criteria, sample size, participant characteristics, genetic variants, treatment type, response definition, clinical outcomes, and main findings.

Of 3372 records screened, 69 studies, reported in 100 publications, met inclusion criteria. These studies included 31,760 participants, of whom 8897 were women. Most publications used a cohort design (n=46) and were conducted in Europe (n=53). The most frequently investigated genes included BDNF (n=17), GSK3β (n=15), SLC6A4 (n=14), COMT (n=7), CREB1 (n=7), DRD2 (n=7), and 5-HT2A (n=7). Mood stabilizers were the most commonly used treatments, followed by antidepressants and total sleep deprivation interventions. Definitions of treatment response and outcome assessment methods varied considerably among studies. Consistent associations with treatment response were observed primarily for BDNF, especially the Val66Met variant (rs6265). Findings for GSK3β, SLC6A4, COMT, CREB1, DRD2, and 5-HT2A were heterogeneous . At least one methodological limitation was reported in 72 publications.

Genetic variants appears to influence pharmacological treatment response in BD. Current evidence suggests more consistent associations for a limited subset of candidate genes. Findings for other variants remain inconsistent because of methodological heterogeneity across studies.