Acute antipyschotic efficacy and side effects in schizophrenia: association with serotonin transporter promoter genotypes |
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Authors: | Dolzan Vita Serretti Alessandro Mandelli Laura Koprivsek Jure Kastelic Matej Plesnicar Blanka Kores |
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Institution: | University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Vrazov trg 2, SI-1000 Ljubljana, Slovenia. vita.dolzan@mf.uni-lj.si |
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Abstract: | BACKGROUND: The serotonin transporter (5-HTT) plays an important role in serotonergic neurotransmission. In the present study, we investigated the effects of the 44 bp insertion/deletion polymorphism in the promoter region of 5-HTT gene (5-HTTLPR) on symptomatology of psychosis and clinical response to antipsychotic drugs. METHODS: In total 56 patients acutely treated with haloperidol or risperidone either for the first episode of schizophrenia, schizophreniform or schizoaffective disorders, or for the relapse of these psychotic disorders after tapering their maintenance treatment, were genotyped for the 5-HTTLPR L and S alleles and for the new A/G functional variant within the L alelle (La/g). Psychopathological symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS) and with Clinical Global Impression (CGI) twice: at 8-12 days after the first dose of antipsychotic and after 4 weeks. Extrapyramidal side effects were assessed with the Simpson-Angus Extrapyramidal Side Effects Scale (EPS), the Barnes Akathisia Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Age, body mass index (BMI), illness duration, drug type and dosage were considered as covariates when analysing association with genetic variants as they were associated with baseline or final BPRS and CGI scores and/or extrapyramidal side effects. 5-HTTLPR was not associated with baseline and final BPRS and CGI scores or with the CGI% reduction. However, the 5-HTTLPR S allele was associated with a lower improvement in BPRS scores (P=0.022) and this effect was even stronger after pooling subjects with S or Lg containing alleles (P=0.006). We did not observe any effect of 5-HTTLPR on acute antipsychotics side effects. CONCLUSION: Present result supports a contribution of serotonin system to neuroleptics efficacy for the treatment of schizophrenia. The analysis of the La/g functional variant may significantly improve the predictive power of 5-HTTLPR genotyping and represent a step further towards the development of the personalized antipsychotic treatment. |
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Keywords: | AIMS Abnormal Involuntary Movement Scale BARS Barnes Akathisia Scale BMI body mass index bp base pairs BPRS Brief Psychiatric Rating Scale CGI Clinical Global Impression DNA deoxyribonucleic acid EPS Simpson–Angus Extrapyramidal Side Effects Scale 5-HT serotonin (5-hydroxytryptamine) 5-HTT serotonin transporter 5-HTTLPR 5-HTT gene linked polymorphic region S allele short allele L allele long allele mRNA messenger ribonucleic acid PANSS Positive and Negative Symptom Scale for Schizophrenia PCR polymerase chain reaction SLC6A4 serotonin transporter gene (solute carrier family 6 [neuro-transmitter transporter serotonin] member 4) |
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