A functional serotonin transporter (5-HTT) polymorphism is associated with psychosis in neuroleptic-free schizophrenics.
The neurotransmitter serotonin has been implicated in the pathophysiology of psychosis. The serotonin transporter (5-HTT) plays a critical role in regulation of serotonergic function. A recently identified polymorphism 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. We investigated whether 5-HTTLPR is associated with psychosis in neuroleptic-free schizophrenic or schizoaffective patients. Fifty patients with schizophrenia or schizoaffective disorder by DSM-III-R criteria were 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 significantly higher BPRS ratings for psychosis than patients with the Is (n = 25) or ss (n = 6) genotypes. Examination of individual items revealed a specific significant increase in intensity of hallucinations in patients with the 5-HTTLPR II genotpe. These data provide preliminary evidence for a role of serotonin in the pathophysiology of hallucinations and may represent the identification of an allelic variant that modifies the complex clinical presentation of schizophrenia.
Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1380, USA.
A K
AK
Malhotra
D
D
Goldman
C
C
Mazzanti
A
A
Clifton
A
A
Breier
D
D
Pickar
D000328:Adult; D017668:Age of Onset; D014150:Antipsychotic Agents; D010054:Brief Psychiatric Rating Scale; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006212:Hallucinations / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000235:genetics* / Q000523:psychology; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
D014150:Antipsychotic Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin