Bárbara Arias1, Chiara Fabbri2, Alessandro Serretti3, Antonio Drago2, Marina Mitjans4, Cristóbal Gastó5, Rosa Catalán5, Lourdes Fañanás1. 1. Unitat d'Antropologia (Dep de Biologia Animal) Facultat de Biologia and Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. 2. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy. 3. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy. Electronic address: alessandro.serretti@unibo.it. 4. Unitat d'Antropologia (Dep de Biologia Animal) Facultat de Biologia and Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona, Spain. 5. Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Centre de Salut Mental Esquerre de l´Eixample, Hospital Clínic i Provincial de Barcelona. Institut d'Investigació Biomèdica Agustí Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Abstract
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.
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 DISC1rs821616 and DAOArs778294 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 DAOArs778294 and DISC1rs6675281-rs1000731 may influence citalopram efficacy.
Authors: C Fabbri; K E Tansey; R H Perlis; J Hauser; N Henigsberg; W Maier; O Mors; A Placentino; M Rietschel; D Souery; G Breen; C Curtis; L Sang-Hyuk; S Newhouse; H Patel; M Guipponi; N Perroud; G Bondolfi; M O'Donovan; G Lewis; J M Biernacka; R M Weinshilboum; A Farmer; K J Aitchison; I Craig; P McGuffin; R Uher; C M Lewis Journal: Pharmacogenomics J Date: 2017-11-21 Impact factor: 3.550