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.
Malhotra
A K
AK
Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1380, USA.
Goldman
D
D
Mazzanti
C
C
Clifton
A
A
Breier
A
A
Pickar
D
D
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