Abstract

The serotonin (5-HT) 1A receptor has been found to be dysregulated in prefrontal cortex and other brain regions in schizophrenia, and 5-HT1A receptor levels in the amygdala have been related to negative schizophrenia symptoms. We have assessed the impact of the functional C-1019G variant of the 5-HT1A receptor on the response to risperidone or haloperidol in a prospective, randomized, double-blind study. Patients were treated for 4 weeks and negative symptoms assessed weekly. The variant influenced the response to risperidone: improvement of negative symptoms by 4.38 points for carriers of the C allele, compared with the GG genotype (1.22 points, P=0.046). In a second independent study of 130 schizophrenia patients treated with atypical antipsychotics, this effect was confirmed (P=0.003). The functional variant of the 5-HT1A receptor thus influences the response of schizophrenia patients to atypical antipsychotics and may be useful in the future to predict the pharmacogenetics of negative symptoms.