Impaired impulse control is associated with a 5-HT2A receptor polymorphism in schizophrenia

The impact of the serotonin2a (5-HT2A) receptor gene on the pathophysiology of schizophrenia is inconclusive despite accumulating evidence implicating the 5-HT2A receptor. To simplify the complexity of genetic analysis, we used an endophenotype approach. The relationship between Continuous Performance Test (CPT) performance and 5-HT2A receptor gene variance was examined. Both patients with schizophrenia (n=255) and healthy volunteers (n=380) were recruited. All were genotyped for the -1438A/G polymorphism and assessed with the CPT. The Positive and Negative Syndrome Scale and the Scale for the Assessment of Negative Symptoms were used to evaluate patients' clinical symptoms. The distribution of the 5-HT2A genotypes between patients and healthy controls was similar. Impulse control in schizophrenic patients, assessed with the false-alarm rate of the CPT, differed significantly between those with different 5-HT2A genotypes. We hypothesize that the 5-HT2A receptor gene is a modifier gene of schizophrenia and suggest that additional studies are warranted.