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Genetic disposition to inflammation and response to antidepressants in major depressive disorder

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Alyson Zwicker, Chiara Fabbri, Marcella Rietschel, Joanna Hauser, Ole Mors, Wolfgang Maier, Astrid Zobel, Anne Farmer, Katherine J. Aitchison, Peter McGuffin, Cathryn M. Lewis, Rudolf Uher

Original languageEnglish
JournalJournal of psychiatric research
Early online date7 Aug 2018
DOIs
Accepted/In press2 Aug 2018
E-pub ahead of print7 Aug 2018

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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.

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