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Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia

Abstract

The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may increase the susceptibility to schizophrenia or may serve as predictors of therapeutic response. We therefore analyzed these polymorphisms as susceptibility factors for schizophrenia by comparison of 684 schizophrenic inpatients with 587 healthy controls. We furthermore compared the therapeutic outcome of schizophrenic patients differentiated by the 5-HTT genotypes. Schizo-affective patients were more frequently homozygous for the 44-bp insertion allele (Odds ratio, OR: 1.6, 95% confidence interval, CI: 1.1–2.3, P < 0.03) than were all other schizophrenic patients and controls. The 17-bp VNTR alleles found were: STin2.7, 9, 10, and 12. Sequence analysis revealed seven different sequence motifs with an invariable arrangement. Patients with schizo-paranoid schizophrenia were more frequently homozygous for the STin2.12 allele than were controls (OR: 1.4, CI: 1.1–1.8, P < 0.007) and all other schizophrenic patients (OR: 1.6, CI: 1.2–2.3). The STin2.9 allele represented a risk factor for the residual subtype of schizophrenia (OR: 6.4, CI: 2.5–16.2, P < 0.001). On the basis of global clinical impressions, as well as measurements with the positive and negative syndrome scale we found no association of the polymorphisms with therapeutic response. In conclusion, the 44-bp polymorphism may be associated with the schizo-affective and the 17-bp VNTR with the residual and schizo-paranoid subtype of schizophrenia, findings which require further biochemical and epidemiological confirmation.

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Acknowledgements

This study was supported by the German Ministry for Research and Technology (BMBF), grants 01EC9408, 01ZZ9511 and 01GG984-1-5. We thank Dr D Filler, S Brockmeier, G Rott, S Strobel, M Lange, S Trautner, K Maronde, O Lüers and N Fichtner for their contributions to this study. We express our appreciation to Prof Dr H Helmchen, Prof Dr B Nickel and Priv Doz Dr A Mackert for supporting this study in their departments.

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Correspondence to J Brockmöller.

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Kaiser, R., Tremblay, PB., Schmider, J. et al. Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia. Mol Psychiatry 6, 179–185 (2001). https://doi.org/10.1038/sj.mp.4000821

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  • DOI: https://doi.org/10.1038/sj.mp.4000821

Keywords

  • schizophrenia
  • serotonin transporter
  • polymorphisms
  • 17-bp VNTR
  • 44-bp insertion/ deletion

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