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-m ethyl-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 t his study, we sought to determine if the APOE epsilon 4 allele influen ces the psychotomimetic response to ketamine in schizophrenics. Eighte en patients genotyped at the APOE locus underwent a double-blind infus ion of ketamine and of placebo. Ketamine-induced alterations in the br ief psychiatric rating scale factors were compared between schizophren ics with and without the APOE epsilon 4 allele. APOE epsilon 4+ schizo phrenics displayed significantly reduced ketamine-induced psychosis, a s compared to epsilon 4- patients. These preliminary data indicate tha t the psychotomimetic response to ketamine may be genetically influenc ed and may provide additional evidence that APOE may modify expression of the positive symptoms in schizophrenia. [Neuropsychopharmacology 1 9:445-448, 1998] Published by Elsevier Science Inc.