Polygenic Contributions to Lithium Augmentation Outcomes in Unipolar Depression

Area of Science:

• Psychiatry
• Genetics
• Pharmacogenomics

Background:

• Lithium augmentation is effective for major depression with inadequate response, but outcomes vary.
• Personalized therapy requires understanding individual treatment prediction.

Purpose of the Study:

• Investigate the association of polygenic risk scores (PRS) for schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) with clinical outcomes after lithium augmentation.
• Assess the potential of PRS in predicting lithium augmentation response.

Main Methods:

• Cohort study of 193 MDD patients undergoing lithium augmentation.
• Calculated disorder-specific PRS using genome-wide association study data.
• Analyzed response (≥50% HAMD-17 reduction) and remission (HAMD-17 ≤7) using Cox models.

Main Results:

• Higher BIP-PRS associated with increased response (HR=1.29) and remission (HR=1.52).
• Lower MDD-PRS associated with better response (HR=0.81).
• No significant association found for SCZ-PRS.

Conclusions:

• Elevated BIP-PRS and reduced MDD-PRS predict favorable lithium augmentation outcomes.
• Disease-related PRS may enhance treatment prediction models for depression.
• Findings support personalized treatment strategies in psychiatric care.