title: Genetic variation in the tryptophan hydroxylase 2 gene moderates depressive symptom trajectories and remission over 8 weeks of escitalopram treatment.
abstract: The serotonin system plays an important role in the pathogenesis of major depressive disorder (MDD) and genetic variations in serotonin-related genes affect the efficacy of antidepressants. The aim of this study was to investigate the relationship between genotypic variation in six candidate serotonergic genes (ADCY9, HTR1B, GNB3, HTR2A, TPH2, SLC6A4) and depressive and anxiety symptom severity trajectories as well as remission following escitalopram treatment. A total of 166 Chinese patients with MDD were treated with escitalopram (open-label) for 8 weeks. TPH2 rs4570625 GG carriers were more likely to achieve depressive and anxiety symptom remission compared with T-allele carriers. At the trend level (P(corrected)=0.05), depressive symptom severity trajectories were moderated by TPH2 rs4570625. Patients with the GT or the GG genotype showed more favorable depressive symptom severity trajectories compared with TT genotype carriers. Polymorphisms in ADCY9, HTR1B, and HTR2A were nominally associated with symptom remission, but did not withstand correction for multiple comparisons. The HTTLPR polymorphism was not included in our final analysis because of a high percentage of missing data. These results suggested that genotypic variation in TPH2 may moderate the therapeutic response to esciatlopram among Chinese patients with MDD.
authors.affiliation: aNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital/Institute of Mental Health bThe Key Laboratory of Mental Health, Ministry of Health (Peking University) cThe University of Melbourne and Peking University Centre for Psychiatry Research and Training, Beijing, China dDepartment of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Yun-Ai
authors.initials: YA
authors.lastname: Su
authors.forename: Ji-Tao
authors.initials: JT
authors.lastname: Li
authors.forename: Wen-Ji
authors.initials: WJ
authors.lastname: Dai
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Liao
authors.forename: Li-Cai
authors.initials: LC
authors.lastname: Dong
authors.forename: Tian-Lan
authors.initials: TL
authors.lastname: Lu
authors.forename: Chad
authors.initials: C
authors.lastname: Bousman
authors.forename: Tian-Mei
authors.initials: TM
authors.lastname: Si
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D015283:Citalopram / Q000008:administration & dosage* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071184:Pharmacogenomic Variants / Q000235:genetics*; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; C000595803:GNB3 protein, human; C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases; C413923:adenylate cyclase 9