Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients

Abstract

Background: Individual differences in serotonin 7 receptor (5-HT7R) may result in variable response to antipsychotics with 5-HT7R antagonism. This study investigated the relationship between single nucleotide polymorphisms (SNPs) in the 5-HT7R gene (HTR7) and the efficacy of second-generation antipsychotic drugs with a high affinity for this receptor in Japanese schizophrenia. Methods: Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. All patients were genotyped for three candidate SNPs (rs12412496, rs7916403, and rs1935349). Patient improvement on the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks was assessed as the primary outcome. PANSS 5-factor scores were investigated as the secondary outcome. Results: Improvement on the PANSS total score and genetic polymorphisms showed no correlation. The rs12412496-rs7916403-rs1935349 A-T-A haplotype was correlated with worse improvement in the cognition score (haplotype frequency: 0.285, p = 0.046, permuted p = 0.043). Conclusion: Our results show that HTR7 variants are not related to the overall improvement in schizophrenia symptoms.

Dose-Dependent Biphasic Action of Quetiapine on AMPK Signalling via 5-HT7 Receptor: Exploring Pathophysiology of Clinical and Adverse Effects of Quetiapine

“…According to the monoaminergic tripartite synaptic transmission hypothesis of mood disorders, it has been suggested that the pharmacodynamic profile of astroglial transmission associated with the hemichannel has a correlation with efficacy in mood disorders [ 26 , 28 , 32 ]. In particular, several pharmacogenetic studies reported that 5-HT7R inhibition played key roles in the pathophysiology of mood disorders other than schizophrenia [ 26 , 33 , 34 , 35 ]. Indeed, a 5-HT7R and 5-HT transporter-inhibiting antidepressant, vortioxetine [ 36 , 37 ], suppresses astroglial L-glutamate release via inhibition of connexin43 (Cx43) trafficking to the plasma membrane [ 31 ].…”

Efficacy of Asenapine in Schizophrenia Resistant to Clozapine Combined with Electroconvulsive Therapy: A Case Report

“…Regarding the association between the 5-HT 7 receptor and schizophrenia, previous studies reported that the 5-HT 7 receptor level was decreased in the prefrontal cortex of schizophrenic patients, and that the genetic polymorphism of Japanese schizophrenic patients was positively associated with the 5-HT 7 receptor gene [19], even with studies showing that 5-HT 7 receptor polymorphisms were not associated with antipsychotic improvement in Japanese schizophrenic patients [20]. Because the affinity of asenapine for these serotonin receptors is higher than that of other antipsychotics, it may be more effective for psychotic symptoms and suicidal behavior.…”

Effects of Subchronic Administrations of Vortioxetine, Lurasidone, and Escitalopram on Thalamocortical Glutamatergic Transmission Associated with Serotonin 5-HT7 Receptor

“…Several clinical studies reported that the 5-HT7R variants are not associated with response to atypical antipsychotics in schizophrenia [41,42], and a significant association was found between responses to positive and negative symptoms with lurasidone and functional polymorphism of 5-HT1AR, but not that of 5-HT7R [43]. Aside from its antipsychotic effects, a functional promoter single-nucleotide polymorphism in the 5-HTR7 gene, rs7905446, which leads to greater 5-HT7R expression [44], was associated with better response to SSRIs in individuals with bipolar disorder and major depression [44].…”