Polygenic score analyses on antidepressant response in late-life depression, results from the IRL-GRey study.

Autor: Elsheikh SSM; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada., Marshe VS; Columbia University Irving Medical Center, New York, NY, USA., Men X; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada., Islam F; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada., Gonçalves VF; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Paré G; Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, Canada.; Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, Canada.; Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, Canada.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada., Felsky D; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada., Kennedy JL; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Mulsant BH; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Reynolds CF 3rd; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA., Lenze EJ; Healthy Mind Lab, Department of Psychiatry, Washington University, St. Louis, MO, USA., Müller DJ; Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada. daniel.mueller@camh.ca.; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada. daniel.mueller@camh.ca.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. daniel.mueller@camh.ca.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. daniel.mueller@camh.ca.; Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany. daniel.mueller@camh.ca.
Jazyk: angličtina
Zdroj: The pharmacogenomics journal [Pharmacogenomics J] 2024 Nov 22; Vol. 24 (6), pp. 38. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1038/s41397-024-00351-0
Abstrakt: Late-life depression (LLD) is often accompanied by medical comorbidities such as psychiatric disorders and cardiovascular diseases, posing challenges to antidepressant treatment. Recent studies highlighted significant associations between treatment-resistant depression (TRD) and polygenic risk score (PRS) for attention deficit hyperactivity disorder (ADHD) in adults as well as a negative association between antidepressant symptom improvement with both schizophrenia and bipolar. Here, we sought to validate these findings with symptom remission in LLD. We analyzed the Incomplete Response in Late Life Depression: Getting to Remission (IRL-GRey) sample consisting of adults aged 60+ with major depression (N = 342) treated with venlafaxine for 12 weeks. We constructed PRSs for ADHD, depression, schizophrenia, bipolar disorder, neuroticism, general intelligence, antidepressant symptom remission and antidepressant percentage symptom improvement using summary statistics from the Psychiatric Genomics Consortium and the GWAS Catalog. Logistic regression was used to test the association of PRSs with venlafaxine symptom remission and percentage symptom improvement, co-varying for the genomic principal components, age, sex and depressive symptoms severity at baseline. We found a nominal (i.e., p value ≤ 0.05) association between symptom remission and both PRS for ADHD and (OR = 1.36 [1.07, 1.73], p = 0.011) and PRS for bipolar disorder (OR = 0.75 [0.58, 0.97], p = 0.031), as well as between percentage symptom improvement and PRS for general intelligence (beta = 6.81 (SE = 3.122), p = 0.03). However, the ADHD association was in the opposite direction as expected, and both associations did not survive multiple testing corrections. Altogether, these findings suggest that previous findings regarding ADHD PRS and antidepressant response (measured with various outcomes) do not replicate in older adults.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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