Original ContributionsHTR1A Gene Polymorphisms and 5-HT1A Receptor Partial Agonist Antipsychotics Efficacy in SchizophreniaTakekita, Yoshiteru MD, PhD*†; Fabbri, Chiara MD*; Kato, Masaki MD, PhD†; Nonen, Shinpei PhD‡; Sakai, Shiho MD†; Sunada, Naotaka MD†; Koshikawa, Yosuke MA†; Wakeno, Masataka MD, PhD†; Okugawa, Gaku MD, PhD†; Kinoshita, Toshihiko MD, PhD†; Serretti, Alessandro MD, PhD* Author Information From the *Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy; †Department of Neuropsychiatry, Kansai Medical University, Osaka; and ‡Department of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan. Received October 15, 2014; accepted after revision February 11, 2015. Reprints: Yoshiteru Takekita, MD, PhD, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, Bologna, 40123, Italy (e-mail: [email protected]). Journal of Clinical Psychopharmacology: June 2015 - Volume 35 - Issue 3 - p 220-227 doi: 10.1097/JCP.0000000000000304 Buy Metrics Abstract Individual differences in serotonin 1A (5-HT1A) receptor may result in variable response to antipsychotics with 5-HT1A receptor partial agonism. We investigated the relationship between 5-HT1A receptor gene (HTR1A) single nucleotide polymorphisms (SNPs) and efficacy of antipsychotics with 5-HT1A receptor partial agonism in Japanese patients with schizophrenia. Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. Candidate SNPs were rs6295 (which affects HTR1A expression and function), rs1364043, rs878567, and rs10042486. Efficacy at week 12 of treatment was evaluated using the Positive and Negative Syndrome Scale (PANSS) 5-factor subscales (excitement/hostility, depression/anxiety, cognition, positive, and negative). Rs1364043 T allele was correlated with the percent change in the PANSS 5-factor negative score (P < 0.01). Haplotype analysis showed that the rs10042486-rs6295-rs1364043 T-C-G haplotype was correlated with worse negative score improvement (haplotype frequency, 0.675; P = 0.014), and the relatively rare T-G-T haplotype correlated with better efficacy (haplotype frequency, 0.05; P = 0.031). This is the first study to show that rs10042486-rs6295-rs1364043 HTR1A variants may be correlated with the improvement of the PANSS 5-factor negative score during treatment with 5-HT1A partial agonist antipsychotics. Studies with larger sample sizes and in different ethnic groups are warranted. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.