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

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

doi:10.1016/j.jpsychires.2018.08.011

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

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

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

668 Downloads (Pure)

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.

Original language	English
Journal	Journal of psychiatric research
Early online date	7 Aug 2018
DOIs	https://doi.org/10.1016/j.jpsychires.2018.08.011
Publication status	E-pub ahead of print - 7 Aug 2018

Keywords

Major depressive disorder
Antidepressant efficacy
Inflammation
C-reactive protein
Polygenic risk score

Access to Document

10.1016/j.jpsychires.2018.08.011

Genetic disposition to inflammation_ZWICKER_Accepted2August2018_GREEN AAM (CC BY-NC-ND)Accepted author manuscript, 396 KBLicence: CC BY-NC-ND

Cite this

@article{99486d0c4bc248aca8055e19bcf7710c,

title = "Genetic disposition to inflammation and response to antidepressants in major depressive disorder",

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-{\AA}sberg 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.",

keywords = "Major depressive disorder, Antidepressant efficacy, Inflammation, C-reactive protein, Polygenic risk score",

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

year = "2018",

month = aug,

day = "7",

doi = "10.1016/j.jpsychires.2018.08.011",

language = "English",

journal = "Journal of psychiatric research",

issn = "0022-3956",

publisher = "Elsevier",

}

TY - JOUR

T1 - Genetic disposition to inflammation and response to antidepressants in major depressive disorder

AU - Zwicker, Alyson

AU - Fabbri, Chiara

AU - Rietschel, Marcella

AU - Hauser, Joanna

AU - Mors, Ole

AU - Maier, Wolfgang

AU - Zobel, Astrid

AU - Farmer, Anne

AU - Aitchison, Katherine J.

AU - McGuffin, Peter

AU - Lewis, Cathryn M.

AU - Uher, Rudolf

PY - 2018/8/7

Y1 - 2018/8/7

N2 - 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.

AB - 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.

KW - Major depressive disorder

KW - Antidepressant efficacy

KW - Inflammation

KW - C-reactive protein

KW - Polygenic risk score

U2 - 10.1016/j.jpsychires.2018.08.011

DO - 10.1016/j.jpsychires.2018.08.011

M3 - Article

SN - 0022-3956

JO - Journal of psychiatric research

JF - Journal of psychiatric research

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this