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Antidepressant-induced mania, rapid cycling and the serotonin transporter gene polymorphism

ABSTRACT

The genes involved in the serotonin system are major candidates in association studies on affective disorders and responses to antidepressants. We studied a functional polymorphism of the serotonin transporter (5-HTT) gene (a 44 bp insertion/deletion in the 5-HTT-linked polymorphic region (5-HTTLPR)) and lifetime history of antidepressant-induced mania (AIM) in a population of 305 patients with bipolar affective disorder. AIM was defined using a broad definition and a restrictive definition. No association was found between the ‘s’ allele of the 5-HTTLPR and AIM for either definition. However, we found an association between the 5-HTTLPR and lifetime history of rapid cycling in a subsample of patients (for allele and genotype distributions: exact probability, p=0.0009 and χ2=9.4; df=1; p=0.002, respectively). These results may help to explain the conflicting association results obtained with the 5-HTT gene polymorphism, in particular with AIM. Indeed, the precise phenotype associated with the 5-HTT gene is unclear. The association between the ‘s’ allele and rapid cycling may provide further evidence for an association between the 5-HTTLPR ‘s’ allele and a pattern of affective instability.

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Acknowledgements

This research was supported by grants from Assistance Publique-Hôpitaux de Paris (CRC), Institut National de la Santé et de la Recherche Médicale (FB, poste d'accueil INSERM) and Fonds National Suisse de la Recherche Scientifique (31-53849.98 and 32-66793.01 to AM).

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Correspondence to F Bellivier.

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Rousseva, A., Henry, C., van den Bulke, D. et al. Antidepressant-induced mania, rapid cycling and the serotonin transporter gene polymorphism. Pharmacogenomics J 3, 101–104 (2003). https://doi.org/10.1038/sj.tpj.6500156

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