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

Kaarina Kowalec; Amber Salter; Kathryn C Fitzgerald; Mitulkumar Patel; Jing Han; Yi Lu; James M Bolton; Carol Hitchon; Charles N Bernstein; Scott Patten; Lesley A Graff; James J Marriott; Ruth Ann Marrie; CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease

doi:10.1016/j.genhosppsych.2022.04.005

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

Gen Hosp Psychiatry. 2022 Jul-Aug:77:21-28. doi: 10.1016/j.genhosppsych.2022.04.005. Epub 2022 Apr 14.

Authors

Affiliations

¹ College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Canada; Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Sweden. Electronic address: [email protected].
² Department of Neurology, UT Southwestern, Dallas, TX, USA.
³ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁴ Department of Physics and Astronomy, Auroral Imaging Group, University of Calgary, Canada.
⁵ Government of Manitoba, Canada.
⁶ Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Sweden.
⁷ Department of Psychiatry, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada; Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada.
⁸ Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada; Department of Rheumatology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada.
⁹ Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada.
¹⁰ Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Canada.
¹¹ Department of Clinical Health Psychology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada.
¹² Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada; Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada.

Abstract

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.

Keywords: Depressive symptoms; Group-based trajectory modelling; Immune-mediated inflammatory disease; PHQ-9; Polygenic risk score.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Depression* / diagnosis
Depression* / genetics
Depressive Disorder, Major* / genetics
Humans
Risk Factors

Grants and funding

R01 MH123724/MH/NIMH NIH HHS/United States