Association between polygenic risk scores combined with clinical characteristics and antidepressant efficacy.

Background: While millions of people suffer from major depressive disorder (MDD), research has shown that individual differences in antidepressant efficacy exist, potentially attributable to various factors. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response are seldom reported. Here, we examined whether PRSs for MDD and schizophrenia (SCZ) are associated with antidepressant effectiveness and the influence of other factors.

Methods: A total of 999 patients were included, and the PRSs for the MDD and SCZ were calculated. The main outcome was a change in the 17-item Hamilton Depression Rating Scale (HAMD17) scores from before to after 2-week treatment. The Mann-Whitney test, Spearman correlation analysis, multiple stepwise linear regression analysis, and interaction analysis were used for statistical analysis.

Results: In the 912 subjects passing quality control, a difference in the HAM-D17 score reduction rate between the MDD phenotype PRS (MDD-PRS) high-risk and the low-risk groups was discovered (P = 0.009), and a correlation was found between the MDD-PRS and the HAM-D17 score reduction rate (r = -0.075, P = 0.024). Moreover, antidepressant efficacy was related to MDD-PRS (β = -4.086, P = 0.039), the Snaith-Hamilton Pleasure Scale-total score (β = -0.009, P = 0.005), and non-first episode (β = -0.039, P < 0.001). However, the result of the interaction analysis was nonsignificant.

Limitations: The main limitation was that only 1309 targeted genes were selected based on pathways known to be involved in MDD and/or antidepressant effects.

Conclusion: These findings suggest a difference in antidepressant efficacy between patients in different MDD-PRS groups. Moreover, the MDD-PRS combined with clinical characteristics partially explained inter-individual differences in antidepressant efficacy.