Alyson Zwicker1, Chiara Fabbri2, Marcella Rietschel3, Joanna Hauser4, Ole Mors5, Wolfgang Maier6, Astrid Zobel6, Anne Farmer7, Katherine J Aitchison8, Peter McGuffin7, Cathryn M Lewis7, Rudolf Uher9. 1. Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health Authority, Halifax, NS, Canada. 2. King's College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, UK; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. 3. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 4. Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poland. 5. Aarhus University Hospital, Risskov, Psychosis Research Unit, Aarhus, Denmark. 6. Department of Psychiatry, University of Bonn, Bonn, Germany. 7. King's College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, UK. 8. Department of Family Medicine, University of Alberta, Edmonton, AB, Canada. 9. Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health Authority, Halifax, NS, Canada; King's College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, UK. Electronic address: uher@dal.ca.
Abstract
BACKGROUND: Inflammation may play an important role in depression and its treatment. A previous study found that increased C-reactive protein (CRP), a marker of systemic inflammation, is associated with worse response to the serotonergic antidepressant escitalopram and better response to the noradrenergic antidepressant nortriptyline. It is unclear whether this reflects genetic disposition to inflammation. METHODS: We analyzed genotype data and weekly Montgomery-Åsberg Depression Rating Scale scores (MADRS) from 755 unrelated individuals obtained over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study. We calculated a polygenic risk score for CRP level based on genome-wide meta-analysis results from the CHARGE Consortium. RESULTS: A higher polygenic risk score for CRP was associated with slightly better response to escitalopram and slightly worse response to nortriptyline, reflected in a statistically significant interaction between polygenic risk score and drug (beta = 1.07, 95% CI = 0.26-1.87, p = 0.0093). DISCUSSION: A differential association between CRP-PRS and antidepressant drug that is in a direction opposite to that found with serum CRP measurement suggests that previously observed effect of inflammation on antidepressant efficacy may be driven by state factors distinct from genetic influences on systemic inflammation.
RCT Entities:
BACKGROUND:Inflammation may play an important role in depression and its treatment. A previous study found that increased C-reactive protein (CRP), a marker of systemic inflammation, is associated with worse response to the serotonergic antidepressant escitalopram and better response to the noradrenergic antidepressant nortriptyline. It is unclear whether this reflects genetic disposition to inflammation. METHODS: We analyzed genotype data and weekly Montgomery-Åsberg Depression Rating Scale scores (MADRS) from 755 unrelated individuals obtained over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study. We calculated a polygenic risk score for CRP level based on genome-wide meta-analysis results from the CHARGE Consortium. RESULTS: A higher polygenic risk score for CRP was associated with slightly better response to escitalopram and slightly worse response to nortriptyline, reflected in a statistically significant interaction between polygenic risk score and drug (beta = 1.07, 95% CI = 0.26-1.87, p = 0.0093). DISCUSSION: A differential association between CRP-PRS and antidepressant drug that is in a direction opposite to that found with serum CRP measurement suggests that previously observed effect of inflammation on antidepressant efficacy may be driven by state factors distinct from genetic influences on systemic inflammation.
Authors: Laura K M Han; Josine E Verhoeven; Audrey R Tyrka; Brenda W J H Penninx; Owen M Wolkowitz; Kristoffer N T Månsson; Daniel Lindqvist; Marco P Boks; Dóra Révész; Synthia H Mellon; Martin Picard Journal: Psychoneuroendocrinology Date: 2019-04-05 Impact factor: 4.905
Authors: Kathleen Van Dyk; Prabha Siddarth; Maura Rossetti; Linda M Ercoli; Michaela M Milillo; Helen Lavretsky Journal: Brain Behav Immun Health Date: 2020-11-07
Authors: Breno S Diniz; Benoit H Mulsant; Charles F Reynolds; Daniel M Blumberger; Jordan F Karp; Meryl A Butters; Ana Paula Mendes-Silva; Erica L Vieira; George Tseng; Eric J Lenze Journal: JAMA Netw Open Date: 2022-06-01