Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response

The serotonergic system is targeted by both antidepressants and atypical an tipsychotic drugs such as clozapine. Genetic variation in the 5-HT5A gene m ight 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 ge ne in a sample of 269 unrelated schizophrenic patients treated with clozapi ne, 112 bipolar patients, 75 unipolar patients and 187 controls. After five -fold correction for multiple testing, allelic association was found with t he -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 recept or gene may be involved in susceptibility to schizophrenia and affective di sorders but not in determining response to clozapine. NeuroReport 11:2017-2 020 (C) 2000 Lippincott Williams & Wilkins.