Catechol-O-methyltransferase Val158Met genotype variation is associated with prefrontal-dependent task performance in schizotypal personality disorder patients and comparison groups.
OBJECTIVE
A single-nucleotide polymorphism of the gene coding for catechol-O-methyltransferase (COMT Val(158)Met) is associated with prefrontal-dependent task performance in schizophrenia. We evaluated the relationship of the COMT genotype with diagnostic status and cognitive performance in schizotypal personality disorder.


METHODS
Unmedicated outpatients with schizotypal personality disorder (SPD; n = 67) and non-schizotypal personality disorder (NSPD; n = 154) by DSM-III-R, and normal control (NC; n = 60) participants were genotyped at the COMT Val(158)Met locus. Of these, 98 Caucasians (23 SPD, 52 NSPD and 23 NC) performed a brief neurocognitive battery: Wisconsin Card Sorting Test (WCST), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Visuospatial Working Memory (DOT) and Visual Delayed Recall (Wechsler Memory Scale Visual Reproduction, WMS-VR).


RESULTS
Allele distribution was not significantly different in the full sample (by chi(2)) for the SPD group compared with either the NC or combined NC/NSPD groups. In analyses of variance of Caucasian individuals, the SPD group performance met or approached significantly worse performance than NC, NSPD or both groups, on the PASAT, CVLT and WMS-VR. In regression analyses of cognitive performance, the COMT genotype was significantly associated with performance on WCST and PASAT, independent of diagnosis, with the Val/Val genotype associated with the worse performance.


CONCLUSIONS
(1) Allelic variation in COMT activity is unrelated to the diagnosis of SPD in this sample. (2) Individuals with SPD exhibit multiple deficits in prefrontal and temporal lobe-dependent tasks. (3) The COMT genotype is related to performance on prefrontal cortex-dependent tasks and may contribute to the deficit in prefrontal-dependent memory processes in SPD as it does in schizophrenia.
Minzenberg
Michael J
MJ
Bronx Veterans Affairs Medical Center, Bronx, New York, 14068, USA. michael.minzenberg@mssm.edu
Xu
Ke
K
Mitropoulou
Vivian
V
Harvey
Philip D
PD
Finch
Thembi
T
Flory
Janine D
JD
New
Antonia S
AS
Goldman
David
D
Siever
Larry J
LJ
D000328:Adult; D019943:Amino Acid Substitution; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D010554:Personality Disorders / Q000201:enzymology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex; D011581:Psychological Tests; D012016:Reference Values; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics; D012569:Schizotypal Personality Disorder / Q000201:enzymology / Q000235:genetics*; D014633:Valine
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine