A FUNCTIONAL SEROTONIN TRANSPORTER (5-HTT) POLYMORPHISM IS ASSOCIATEDWITH PSYCHOSIS IN NEUROLEPTIC-FREE SCHIZOPHRENICS

The neurotransmitter serotonin has been implicated in the pathophysiol ogy of psychosis. The serotonin transporter (5-HTT) plays a critical r ole in regulation of serotonergic function. A recently identified poly morphism in the promoter region of the 5-HTT gene (5-HTTLPR) produces significant differences in 5-HTT expression and function and was found to be associated with anxiety-related traits in healthy volunteers. W e investigated whether 5-HTTLPR is associated with psychosis in neurol eptic-free schizophrenic or schizoaffective patients. Fifty patients w ith schizophrenia or schizoaffective disorder by DSM-III-R criteria we re genotyped at 5-HTTLPR and underwent double-blind Brief Psychiatric Rating Scale (BPRS) ratings while neuroleptic-free for approximately 4 weeks. Patients with the 5-HTTLPR II genotype (n = 19) had significan tly higher BPRS ratings for psychosis than patients with the is (n = 2 5) or ss (n = 6) genotypes. Examination of individual items revealed a specific significant increase in intensity of hallucinations in patie nts with the 5-HTTLPR Il genotype. These data provide preliminary evid ence for a role of serotonin in the pathophysiology of hallucinations and may represent the identification of an allelic variant that modifi es the complex clinical presentation of schizophrenia.