Abstract
BackgroundThere are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia.MethodsIn total, 233 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 89 participants received risperidone, 69 olanzapine, 48 aripiprazole, and 27 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Four single nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs1128503, rs2032582, and rs2235048) were genotyped using the TaqMan method.ResultsFor aripiprazole, sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier–rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier–rs2235048 non-C allele carrier group. In addition, in the aripiprazole group, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. However, there were no significant associations between ANS activity and ABCB1 gene polymorphisms in the risperidone, olanzapine, and quetiapine groups. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642–rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582).ConclusionWe suggest that ABCB1 genetic polymorphisms affect aripiprazole-related ANS dysfunction but do not affect risperidone-, olanzapine-, or quetiapine-related ANS dysfunction.
Highlights
There are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction
Body mass index (BMI) body mass index, PANSS Positive and Negative Syndrome Scale, ln natural log-transformed, HF high frequency, LF low frequency, TP total power aThe daily doses of antipsychotic drugs were converted to an approximate chlorpromazine equivalent bThe daily doses of anticholinergic antiparkinsonian drugs were converted to an approximate biperiden equivalent cThe daily doses of benzodiazepine were converted to an approximate diazepam equivalent
BMI body mass index, PANSS Positive and Negative Syndrome Scale aThe daily doses of antipsychotic drugs were converted to an approximate chlorpromazine equivalent bThe daily doses of anticholinergic antiparkinsonian drugs were converted to an approximate biperiden equivalent cThe daily doses of benzodiazepine were converted to an approximate diazepam equivalent (p = .067) in the multiple regression analysis
Summary
There are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. To clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia. We found individual differences in ANS activity in patients with schizophrenia, even among those taking the same atypical antipsychotic (risperidone, olanzapine, aripiprazole, or quetiapine). Other studies reported that ABCB1 gene polymorphisms affect the plasma concentrations of antipsychotics [15, 16]. We previously reported associations of ABCB1 gene polymorphisms with ANS dysfunction following treatment with aripiprazole in patients with schizophrenia [23]. Few studies have investigated the effects of ABCB1 gene polymorphisms on ANS dysfunction due to several other atypical antipsychotics in schizophrenia
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