Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications.
BACKGROUND
The gene encoding catechol-O-methyltransferase (COMT), an enzyme that regulates prefrontal cortex dopamine, contains a common functional polymorphism (val(108/158)met) that influences prefrontal cortex function in an allelic dose-dependent manner. A recent study reported that the COMT val(108/158)met polymorphism influences cognitive- and physiologic-related prefrontal cortex responses to antipsychotic treatment. The present study tested the effects of several COMT polymorphisms on the cognitive response to antipsychotic medication in patients with schizophrenia.


METHODS
Twenty inpatients with schizophrenia or schizoaffective disorder (5 with the val-val genotype, 11 with val-met, and 4 with met-met) were administered cognitive tests at two time points: once after 4 weeks of treatment with antipsychotic medication and once after 4 weeks of placebo administration, according to a counterbalanced, double-blind, within-subject study design.


RESULTS
Patients homozygous for the COMT met allele displayed significant improvement on the working memory task after treatment. Patients homozygous for the COMT val allele did not show working memory improvement with treatment. Other COMT polymorphisms were not associated with significant differences between treatment and placebo conditions.


CONCLUSIONS
These results support other data suggesting that the COMT val(108/158)met polymorphism might be an important factor in the cognitive response to antipsychotic medication.
Weickert
Thomas W
TW
National Institutes of Health, National Institute of Mental Health, Clinical Brain Disorders Branch, Building 10, Room 4C 101, MSC 1379, Bethesda, MD 20892, USA. weickert@intra.nimh.nih.gov
Goldberg
Terry E
TE
Mishara
Aaron
A
Apud
Jose A
JA
Kolachana
Bhaskar S
BS
Egan
Michael F
MF
Weinberger
Daniel R
DR
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008609:Mental Status Schedule; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D014633:Valine / Q000235:genetics
D014150:Antipsychotic Agents; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine