Antidepressant Outcomes Predicted by Genetic Variation in Corticotropin-Releasing Hormone Binding Protein

Chloe P O'Connell; Andrea N Goldstein-Piekarski; Charles B Nemeroff; Alan F Schatzberg; Charles Debattista; Tania Carrillo-Roa; Elisabeth B Binder; Boadie W Dunlop; W Edward Craighead; Helen S Mayberg; Leanne M Williams

doi:10.1176/appi.ajp.2017.17020172

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Antidepressant Outcomes Predicted by Genetic Variation in Corticotropin-Releasing Hormone Binding Protein

Journal article

Open access

Peer reviewed

Antidepressant Outcomes Predicted by Genetic Variation in Corticotropin-Releasing Hormone Binding Protein

Chloe P O'Connell, Andrea N Goldstein-Piekarski, Charles B Nemeroff, Alan F Schatzberg, Charles Debattista, Tania Carrillo-Roa, Elisabeth B Binder, Boadie W Dunlop, W Edward Craighead, Helen S Mayberg, …

The American journal of psychiatry, Vol.175(3), pp.251-261

2018-03-01

DOI: https://doi.org/10.1176/appi.ajp.2017.17020172

PMID: 29241359

Abstract

Humans

Middle Aged

Genotype

Male

Treatment Outcome

Venlafaxine Hydrochloride - therapeutic use

Depression - genetics

Antidepressive Agents - therapeutic use

Young Adult

Carrier Proteins - genetics

Depression - drug therapy

Homozygote

Adolescent

Sertraline - therapeutic use

Polymorphism, Single Nucleotide - genetics

Adult

Citalopram - therapeutic use

Female

Aged

Genetic variation within the hypothalamic-pituitary-adrenal (HPA) axis has been linked to risk for depression and antidepressant response. However, these associations have yet to produce clinical gains that inform treatment decisions. The authors investigated whether variation within HPA axis genes predicts antidepressant outcomes within two large clinical trials. The test sample comprised 636 patients from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) who completed baseline and 8-week follow-up visits and for whom complete genotyping data were available. The authors tested the relationship between genotype at 16 candidate HPA axis single-nucleotide polymorphisms (SNPs) and treatment outcomes for three commonly used antidepressants (escitalopram, sertraline, and extended-release venlafaxine), using multivariable linear and logistic regression with Bonferroni correction. Response and remission were defined using the Hamilton Depression Rating Scale. Findings were then validated using the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study of outcome predictors in treatment-naive patients with major depression. The authors found that the rs28365143 variant within the corticotropin-releasing hormone binding protein (CRHBP) gene predicted antidepressant outcomes for remission, response, and symptom change. Patients homozygous for the G allele of rs28365143 had greater remission rates, response rates, and symptom reductions. These effects were specific to drug class. Patients homozygous for the G allele responded significantly better to the selective serotonin reuptake inhibitors escitalopram and sertraline than did A allele carriers. In contrast, rs28365143 genotype was not associated with treatment outcomes for the serotonin norepinephrine reuptake inhibitor venlafaxine. When patients were stratified by race, the overall effect of genotype on treatment response remained. In the validation sample, the GG genotype was again associated with favorable antidepressant outcomes, with comparable effect sizes. These findings suggest that a specific CRHBP SNP, rs28365143, may have a role in predicting which patients will improve with antidepressants and which type of antidepressant may be most effective. The results add to the foundational knowledge needed to advance a precision approach to personalized antidepressant choices.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.5 Neuroscience; 1.5.420 Cortisol
Web Of Science research areas: Psychiatry
ESI research areas: Psychiatry/Psychology

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Title: Antidepressant Outcomes Predicted by Genetic Variation in Corticotropin-Releasing Hormone Binding Protein
Creators: Chloe P O'Connell - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Andrea N Goldstein-Piekarski - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Charles B Nemeroff - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Alan F Schatzberg - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Charles Debattista - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Tania Carrillo-Roa - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Elisabeth B Binder - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Boadie W Dunlop - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
W Edward Craighead - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Helen S Mayberg - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Leanne M Williams - From the School of Medicine and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, Calif.; the Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami; the Department of Translational Research in Psychiatry, Max Planck Institute for Psychiatry, Munich; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; and the Department of Psychology, Emory University, Atlanta
Publication Details: The American journal of psychiatry, Vol.175(3), pp.251-261
Publisher: United States
Grant note: F32 MH108299 / NIMH NIH HHS T32 MH019938 / NIMH NIH HHS M01 RR000039 / NCRR NIH HHS UL1 RR025008 / NCRR NIH HHS KL2 TR001083 / NCATS NIH HHS TL1 TR001084 / NCATS NIH HHS R01 MH101496 / NIMH NIH HHS L30 MH108115 / NIMH NIH HHS R01 MH080880 / NIMH NIH HHS K23 MH086690 / NIMH NIH HHS P50 MH077083 / NIMH NIH HHS
Academic Unit: UMMG Dept of Psychiatry & Behavioral Sciences
Language: English
Resource Type: Journal article
PMID: 29241359
Record Identifier: 991031577335702976