Depressive symptom trajectories and polygenic risk scores in individuals with an immune-mediated inflammatory disease

Objective: To develop group-based trajectories of depressive symptoms in immune-mediated inflammatory disease (IMID) to understand their evolution and identify any associated factors, with the overall goal of identifying those at highest risk of higher depressive symptom burden. Method: 922 participants had an IMID or anxiety/depression. The PHQ-9 was administered at four visits, and polygenic risk scores (PRS) for major depressive disorder, depressive symptoms, and body mass index (BMI) were generated. Group-based trajectory modelling of PHQ-9 scores estimated distinct trajectories. Regression tested whether specific factors were associated with the trajectories. Mediation analyses assessed whether IMID mediated the association between BMI PRS and trajectories. Results: Three trajectories were identified. Regression demonstrated those in Group 3 (‘high symptoms’) had significantly higher PRS for the three traits, compared to Group 1 (‘minimal symptoms’) (OR: 1.34–1.66, P < 0.01). Stratified analyses in the IMID subgroup revealed an increased effect for BMI PRS in Group 3 (OR: 2.31, P < 0.001), in contrast, BMI PRS was no longer associated in the non-IMID sample. No significant indirect effect of BMI PRS on depressive symptoms trajectories was identified via IMID. Conclusions: A significant association between polygenicity and PHQ-9 trajectories supports a role for genetic inheritance in the variability in depressive symptoms in IMID.