An investigation of the α_1A-adrenergic receptor gene and antipsychotic-induced side-effects

Antipsychotic treatment is hampered by the induction of side-effects such as tardive dyskinesia (TD), weight gain, sedation and extrapyramidal side-effects (EPS). Identification of the factors related to their development would facilitate their avoidance and the improvement of antipsychotic treatment. It has been hypothesised that genetic variants in drug targeted receptors may contribute to the development of side-effects. In this study, we have investigated the possible influence of genetic variants (-563-C/T, -4155-G/C and -4884-A/ G) of the α₁A-adrenergic receptor, an important target of atypical antipsychotic drugs, and development of side-effects after antipsychotic medication in a sample of N = 427 US Caucasian patients. We found several marginal associations (p<0.05) between α ₁A-adrenergic genetic variants and antipsychoti-c-induced side-effects which did not reach statistical significance after corrections for multiple analyses. These results do not support a major role of α₁A-adrenergic genetic variants in obesity and other side-effects observed after prolonged treatment with antipsychotic medications.