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The serotonin transporter and clozapine response

Molecular Psychiatry volume 5, pages 124–125 (2000)Cite this article

Two hundred and sixty-eight schizophrenic patients were included in this study. The patients were white Caucasians of British origin and were collected in the London, Cambridge and Burnley areas. All patients had a DSM-IIIR or DSM-IV diagnosis of schizophrenia and had shown no improvement after treatment with at least two neuroleptics before undergoing treatment with clozapine. Treatment response was assessed at least 3 months after optimisation of therapeutic doses. Response was evaluated using the Global Assessment Scale (GAS)6 and an improvement of 20 points was considered as the threshold for appropriate response. According to this criteria the sample included 180 subjects who improved satisfactorily and 88 patients who showed poor response to clozapine treatment. Informed consent was obtained from all the subjects included in the study.

The 5-HTT VNTR in intron 2 and the biallelic polymorphism in the linked polymorphic region (5-HTTLPR) were genotyped following the methods previously described.7, 8 The genotyping results are summarised in Table 1. Chi-square tests were calculated for all comparisons using the SPSS (version 8.0) and EpiInfo (version 6) statistical packages. Haplotype analyses were performed using the EH programme (version 1.11). This sample had an 80% power to detect association with an odds ratio of 2.2. No differences were observed in allele or genotype frequencies of the 5-HTT VNTR polymorphism in intron 2 when comparing patients who showed marked improvement with patients who did not appropriately respond to clozapine. Analysis of the 5-HTTLPR results showed that homozygotes for the short allele (480 bp/480 bp) were more frequent among treatment non-responders than heterozygotes (520 bp/480 bp) and homozygotes for the long variant (520 bp/520 bp), although this difference was not statistically significant (χ2 = 2.99, P = 0.08; odds ratio = 1.70, 95% CI = 0.89–3.24). Haplotype combinations of both polymorphisms did not improve the association with clozapine response.

Table 1 Genotype frequencies of the 5-HTT VNTR (intron 2) and the 5-HTTLPR polymorphisms in a sample of clozapine-treated patients
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  1. Department of Psychological Medicine, Section of Clinical Neuropharmacology, Institute of Psychiatry, Denmark Hill, London, SE5 8AF, UK

    M J Arranz, A A Bolonna, J Munro, C J Curtis, D A Collier & R W Kerwin

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  1. M J Arranz
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  2. A A Bolonna
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  3. J Munro
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  4. C J Curtis
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  5. D A Collier
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  6. R W Kerwin
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Correspondence to M J Arranz.

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Arranz, M., Bolonna, A., Munro, J. et al. The serotonin transporter and clozapine response. Mol Psychiatry 5, 124–125 (2000). https://doi.org/10.1038/sj.mp.4000652

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