Brief Report

Polygenic Contributions to Lithium Augmentation Outcomes in Unipolar Depression

JAMA Psychiatry 10.1001/jamapsychiatry.2025.2039

September 03, 2025 at 11:00 AM EDT

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Are polygenic risk scores (PRS) for major psychiatric disorders associated with favorable treatment outcomes after lithium augmentation (LA) in major depression?In this cohort study with 193 patients with major depressive disorder (MDD) who did not respond to antidepressants, the PRS for bipolar disorder (BIP) was significantly associated with response and remission after at least 4 weeks of LA. Additionally, we found an association between the MDD-PRS and LA response.Individuals with a higher polygenic burden for BIP and lower polygenic burden for MDD are more likely to experience favorable treatment outcomes following LA, offering new opportunities for personalized medicine approaches.

Corresponding Author: Julia Kraft, MSc, Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany (julia.kraft@charite.de).

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