TY - JOUR
T1 - Early antidepressant efficacy modulation by glutamatergic gene variants in the STAR*D
AU - Fabbri, Chiara
AU - Drago, Antonio
AU - Serretti, Alessandro
N1 - Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.
PY - 2013/7
Y1 - 2013/7
N2 - The glutamatergic system has been suggested as a modulator of rapid antidepressant response. Thus, 44 glutamatergic genes were selected according to the literature and investigated in 1541 major depressive patients from the STAR*D genome wide dataset. Outcomes of interest were early response (2nd week) and late response (from the 4th to the 14th week) compared to non-response and stability of response through the STAR*D level 1. A complete agglomerative clustering, based on pairwise identity-by-state (IBS) matrix, was applied in order to control for genetic admixture. A chi-square test was employed as exploratory analysis and a logistic regression was employed to corroborate SNPs associated to the outcomes at p<0.001. Covariates were selected accordingly to their impact on phenotypes. A Bonferroni correction was applied. PLINK served for the analysis. About 1995 SNPs were available after quality control. Our results suggested that the rs1083801 within the GRM7 (glutamate receptor, metabotropic 7) gene was associated to early response under a recessive model (GG genotype observed in 14.34% of early responders vs 5.25% of late responders, OR=0.33, 95% CI=0.21-0.54, p=6.41e-06. GG genotype observed in 5.34% of non-responders, OR=0.33, 95% CI=0.20-0.56, p=4.07e-05). The result was confirmed in the white non-Hispanic group (GG genotype observed in 17.46% of early responders vs 5.81% of the rest of the sample, OR=0.29, 95% CI=0.18-0.46, p=2.04e-07). No marker predicted the stability of response. Glutamatergic genes may be useful markers of early antidepressant efficacy. This result may be relevant in further understanding the pathophysiology of the drug induced antidepressant effect.
AB - The glutamatergic system has been suggested as a modulator of rapid antidepressant response. Thus, 44 glutamatergic genes were selected according to the literature and investigated in 1541 major depressive patients from the STAR*D genome wide dataset. Outcomes of interest were early response (2nd week) and late response (from the 4th to the 14th week) compared to non-response and stability of response through the STAR*D level 1. A complete agglomerative clustering, based on pairwise identity-by-state (IBS) matrix, was applied in order to control for genetic admixture. A chi-square test was employed as exploratory analysis and a logistic regression was employed to corroborate SNPs associated to the outcomes at p<0.001. Covariates were selected accordingly to their impact on phenotypes. A Bonferroni correction was applied. PLINK served for the analysis. About 1995 SNPs were available after quality control. Our results suggested that the rs1083801 within the GRM7 (glutamate receptor, metabotropic 7) gene was associated to early response under a recessive model (GG genotype observed in 14.34% of early responders vs 5.25% of late responders, OR=0.33, 95% CI=0.21-0.54, p=6.41e-06. GG genotype observed in 5.34% of non-responders, OR=0.33, 95% CI=0.20-0.56, p=4.07e-05). The result was confirmed in the white non-Hispanic group (GG genotype observed in 17.46% of early responders vs 5.81% of the rest of the sample, OR=0.29, 95% CI=0.18-0.46, p=2.04e-07). No marker predicted the stability of response. Glutamatergic genes may be useful markers of early antidepressant efficacy. This result may be relevant in further understanding the pathophysiology of the drug induced antidepressant effect.
KW - Adult
KW - African Americans/genetics
KW - Antidepressive Agents/therapeutic use
KW - Citalopram/therapeutic use
KW - Databases, Genetic
KW - Depressive Disorder, Major/drug therapy
KW - European Continental Ancestry Group/genetics
KW - Female
KW - Genotype
KW - Glutamic Acid/genetics
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Receptors, Metabotropic Glutamate/genetics
KW - Signal Transduction/genetics
KW - Time Factors
KW - Treatment Outcome
U2 - 10.1016/j.euroneuro.2012.07.006
DO - 10.1016/j.euroneuro.2012.07.006
M3 - Journal article
C2 - 22884879
SN - 0924-977X
VL - 23
SP - 612
EP - 621
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 7
ER -