Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response |
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Authors: | Birkett J T Arranz M J Munro J Osbourn S Kerwin R W Collier D A |
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Institution: | Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London, UK. |
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Abstract: | The serotonergic system is targeted by both antidepressants and atypical antipsychotic drugs such as clozapine. Genetic variation in the 5-HT5A gene might be involved in susceptibility to depression, the major psychoses or in influencing clinical response to treatment. To examine this hypothesis we genotyped two polymorphisms (-19G/C; 12A/T) in the human 5-HT5A receptor gene in a sample of 269 unrelated schizophrenic patients treated with clozapine, 112 bipolar patients, 75 unipolar patients and 187 controls. After five-fold correction for multiple testing, allelic association was found with the -19G/C polymorphism and bipolar affective disorder, (p = 0.025; OR 0.56), unipolar depression (p = 0.004; OR 0.52) and schizophrenia (p = 0.036; OR 0.67) indicating a potential protective effect of the G19 allele. For the 12A/T polymorphism allelic association was observed with unipolar depression only (p = 0.004). We conclude that allelic variation in the human 5-HT5A receptor gene may be involved in susceptibility to schizophrenia and affective disorders but not in determining response to clozapine. |
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