The apolipoprotein E epsilon 4 allele is associated with blunting of ketamine-induced psychosis in schizophrenia. A preliminary report.
Interindividual differences in the psychotomimetic response to the N-methyl-d-aspartate receptor antagonist ketamine are commonly observed. The apolipoprotein E (APOE) epsilon 4 allele has been associated with reduced severity of positive psychotic symptoms in schizophrenia. In this study, we sought to determine if the APOE epsilon 4 allele influences the psychotomimetic response to ketamine in schizophrenics. Eighteen patients genotyped at the APOE locus underwent a double-blind infusion of ketamine and of placebo. Ketamine-induced alterations in the brief psychiatric rating scale factors were compared between schizophrenics with and without the APOE epsilon 4 allele. APOE epsilon 4+ schizophrenics displayed significantly reduced ketamine-induced psychosis, as compared to epsilon 4-patients. These preliminary data indicate that the psychotomimetic response to ketamine may be genetically influenced and may provide additional evidence that APOE may modify expression of the positive symptoms in schizophrenia.
Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
A K
AK
Malhotra
A
A
Breier
D
D
Goldman
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L
Picken
D
D
Pickar
D000328:Adult; D000339:Affect / Q000187:drug effects; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology; D010054:Brief Psychiatric Rating Scale; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D011605:Psychoses, Substance-Induced / Q000235:genetics* / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D007649:Ketamine