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Influence of TAAR6 polymorphisms on response to aripiprazole
Authors:Alessandro Serretti  Chi-Un Pae  Alberto Chiesa  Laura Mandelli  Diana De Ronchi
Institution:1. Institute of Psychiatry, University of Bologna, Bologna, Italy;2. Department of Psychiatry, Holy Family Hospital, The Catholic University of Korea College of Medicine, Bucheon, Kyounggi-Do, Republic of Korea;3. Department of Psychiatry and Behavioral Medicines, Duke University Medical Center, Durham, NC, United States
Abstract:

Background

There is some evidence suggesting a role of TAAR6 in schizophrenia. The aim of the present study is to investigate possible influences of a panel of markers in TAAR6 (rs8192625, rs4305745, rs4305746, rs6903874, rs6937506) on clinical outcomes and side effects in a sample of Korean schizophrenic aripiprazole treated patients.

Methods

Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 using CGI-S, CGI-I, BPRS and SANS. Side effects were evaluated through SAS, BAS and AIMS. Multivariate analysis of covariance (MANCOVA) was used to test possible influences of single SNPs on clinical and safety scores. Tests for associations using multi-marker haplotypes were performed using the statistics environment “R”.

Results

A significant time per genotype interaction was found between rs4305746 in repeated measures of ANOVA on BPRS scores (F = 2.45, df = 10,365, p = 0.008). In particular G/A and A/A genotype patients were more likely to improve over time as compared to carriers of the G/G genotype. Permutation analysis confirmed a significant effect of rs4305746 on course of BPRS scores over time (p = 0.007). Haplotype analysis did not reveal any significant association with clinical and safety scores at any time.

Conclusion

A possible association could exist between some genotypes in TAAR6 and response to aripiprazole. However, several limitations characterize the present work, such as small sample size, the finding related to a single scale and the possibility of false positive findings, thus further investigation is required.
Keywords:AIMS  Abnormal Involuntary Movement Scale  BAS  Barnes Akathisia Scale  BPRS  Brief Psychiatric Rating Scale  CGI  Clinical Global Impression  SANS  Schedule for the Assessment of Negative Symptoms  SAS  Simpson&ndash  Angus Scale for Extrapyramidal Symptoms  SNP  single nucleotide polymorphism  TAAR  trace amine-associated receptor
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