Schizotypy is a psychological concept which describes a continuum of personality characteristics and experiences related to psychosis and in particular, schizophrenia. Researchers at the University of Manchester led by Prof Bill Deakin asked members of the university to complete the O-LIFE schizotypy questionnaire. Approximately 1,206 responded of which 60 were interviewed and performed a signal detection task (SDT). High schizotypy participants made more false alarm responses, perceiving spoken human voice embedded in white noise when no voice was present. They were also faster to respond, suggesting a “jumping-to-conclusions” decision making style, as reported described in patients with delusions. Eight high-schizotypy participants completed an event-related auditory SDT in an fMRI scanner. False alarm responses were associated with patterns of brain activation which resembled those reported in studies of auditory hallucinations in schizophrenia. In a proof of concept, pilot study buccal swabs were obtained from 100 subjects. 96% of samples could be genotyped successfully for a number of polymorphisms. A statistically significant association was found between an intronic SNP (rs165599) in the COMT gene and schizotypy score, a SNP previously strongly associated with schizophrenia and with performance and brain responses on an n-back task. Researchers at the University of Manchester are setting up web-based recruitment for a full-scale genetic study. The aim is to validate this assay with two or more antipsychotic reference drugs on psychological processes thought to directly underpin characteristic symptoms of schizophrenia. Neuropsychological tests will be used to probe the key psychological processes and fMRI will be used to visualise brain systems engaged by them. The study will be carried out in healthy volunteers selected for high self-rated scores on schizotypy, a personality measure of psychosis-proneness. The advantages of this assay are that the efficacy of new antipsychotics may be determined in drug-free volunteers.