TY - JOUR
T1 - DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy
AU - Arias, Bárbara
AU - Fabbri, Chiara
AU - Serretti, Alessandro
AU - Drago, Antonio
AU - Mitjans, Marina
AU - Gastó, Cristóbal
AU - Catalán, Rosa
AU - Fañanás, Lourdes
N1 - Copyright © 2014 Elsevier B.V. All rights reserved.
PY - 2014/10
Y1 - 2014/10
N2 - BACKGROUND: Major depressive disorder (MDD) is a common disease with high morbidity and still unsatisfying treatment response. Both MDD pathogenesis and antidepressant effect are supposed to be strongly affected by genetic polymorphisms. Among promising candidate genes, distrupted in schizophrenia 1 (DISC1), translin-associated factor X (TSNAX) and D-amino acid oxidase activator (DAOA) were suggested since their regulator role in neurodevelopment, neuroplasticity and neurotransmission, and previous evidence of cross-involvement in major psychiatric diseases.METHODS: The present paper investigated the role of 13 SNPs within the reported genes in MDD susceptibility through a case-control (n=320 and n=150, respectively) study and in citalopram efficacy (n=157). Measures of citalopram efficacy were response (4th week) and remission (12th week). Pharmacogenetic findings were tested in the STAR(⁎)D genome-wide dataset (n=1892) for replication.RESULTS: Evidence of association among rs3738401 (DISC1), rs1615409 and rs766288 (TSNAX) and MDD was found (p=0.004, p=0.0019, and p=0.008, respectively). A trend of association between remission and DISC1 rs821616 and DAOA rs778294 was detected, and confirmation was found for rs778294 by repeated-measure ANOVA (p=0.0008). In the STAR(⁎)D a cluster of SNPs from 20 to 40Kbp from DISC1 findings in the original sample was associated with citalopram response, as well as rs778330 (12,325bp from rs778294).LIMITATIONS: Relatively small size of the original sample and focus on only three candidate genes.CONCLUSIONS: The present study supported a role of DISC1-TSNAX variants in MDD susceptibility. On the other hand, genetic regions around DAOA rs778294 and DISC1 rs6675281-rs1000731 may influence citalopram efficacy.
AB - BACKGROUND: Major depressive disorder (MDD) is a common disease with high morbidity and still unsatisfying treatment response. Both MDD pathogenesis and antidepressant effect are supposed to be strongly affected by genetic polymorphisms. Among promising candidate genes, distrupted in schizophrenia 1 (DISC1), translin-associated factor X (TSNAX) and D-amino acid oxidase activator (DAOA) were suggested since their regulator role in neurodevelopment, neuroplasticity and neurotransmission, and previous evidence of cross-involvement in major psychiatric diseases.METHODS: The present paper investigated the role of 13 SNPs within the reported genes in MDD susceptibility through a case-control (n=320 and n=150, respectively) study and in citalopram efficacy (n=157). Measures of citalopram efficacy were response (4th week) and remission (12th week). Pharmacogenetic findings were tested in the STAR(⁎)D genome-wide dataset (n=1892) for replication.RESULTS: Evidence of association among rs3738401 (DISC1), rs1615409 and rs766288 (TSNAX) and MDD was found (p=0.004, p=0.0019, and p=0.008, respectively). A trend of association between remission and DISC1 rs821616 and DAOA rs778294 was detected, and confirmation was found for rs778294 by repeated-measure ANOVA (p=0.0008). In the STAR(⁎)D a cluster of SNPs from 20 to 40Kbp from DISC1 findings in the original sample was associated with citalopram response, as well as rs778330 (12,325bp from rs778294).LIMITATIONS: Relatively small size of the original sample and focus on only three candidate genes.CONCLUSIONS: The present study supported a role of DISC1-TSNAX variants in MDD susceptibility. On the other hand, genetic regions around DAOA rs778294 and DISC1 rs6675281-rs1000731 may influence citalopram efficacy.
KW - Adult
KW - Analysis of Variance
KW - Antidepressive Agents/therapeutic use
KW - Antidepressive Agents, Second-Generation/therapeutic use
KW - Case-Control Studies
KW - Depressive Disorder, Major/drug therapy
KW - Female
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide/genetics
KW - Spain
KW - Treatment Outcome
U2 - 10.1016/j.jad.2014.06.048
DO - 10.1016/j.jad.2014.06.048
M3 - Journal article
C2 - 25043320
SN - 0165-0327
VL - 168
SP - 91
EP - 97
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -