Polygenic scores and symptom severity change after internet-delivered cognitive behaviour therapy for depression and anxiety

Depressive and anxiety disorders are leading causes of disability globally. Therapist-guided, Internet-delivered cognitive behaviour therapy (ICBT) is an established treatment for depression and anxiety, but a considerable proportion of treated patients do not achieve sufficient improvement. Predicting symptom changes based solely on clinical variables is challenging, and genetic data could offer additional insights into who might benefit most from ICBT. We conducted a study of 2,668 adults (62% women, average age 35.6) from the Swedish MULTI-PSYCH cohort, to investigate the association between polygenic scores (PGS) for eight psychiatric and cognitive traits and symptom change after ICBT. All participants had been diagnosed with depression, panic disorder or social anxiety disorder. The primary outcome was a harmonised symptom score. Using large discovery data sets, PGSs were computed for ADHD, autism spectrum disorder, bipolar disorder, major depressive disorder and schizophrenia, cross-disorder psychopathology, educational attainment, and intelligence. Linear mixed-effects models identified a significant negative association between PGS for educational attainment (PGS-EDU) and symptom severity in the adjusted model (B = - 0.69, p = 0.034), suggesting that a higher PGS-EDU was associated with lower symptom severity. There was also a significant PGS-EDU*time interaction, indicating that PGS-EDU also influenced the symptom change rate. When excluding outliers, these effects remained statistically significant. No other PGSs were statistically significant. Sensitivity analysis showed that self-reported education level provided a stronger association to the outcome than PGS-EDU, indicating that the potential clinical applications of PGS are currently limited. While these results await replication, they could have important implications for how the ICBT could be adapted to suit a wider portion of the population.