Associations between COMTVal158Met polymorphism and cognition: direct or indirect effects?
BACKGROUND
Previous work suggests that reaction time variability (RTV) in attentional tasks, as a measure of cognitive stability, is associated with degree of Val loading in COMT Val(158)Met genotype, and that this association may be relevant for the aetiology of schizophrenia. This study examined (i) to what degree RTV pertaining to tasks of varying cognitive complexity would be associated with increased risk for schizophrenia and (ii) to what degree this would be mediated by Val loading.


METHODS
COMT genotyping was investigated in a sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21 controls. All participants performed the Flanker continuous performance test.


RESULTS
Schizophrenia liability was associated with number of correct trials of the Flanker test, but not with RTV, and this association was not mediated by COMT Val(158)Met genotype. Similarly, Met loading was associated with number of correct trials and with RTV, but this was not mediated by schizophrenia liability.


CONCLUSIONS
Associations between COMT Val(158)Met genotype and RTV do not appear to reflect transmission of schizophrenia liability in families. Differential associations with Val and Met alleles across studies suggest indirect effects through gene-gene interactions or the influence of a functional polymorphism near COMT Val(158)Met.
Krabbendam
Lydia
L
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO BOX 616 (VIJV), 6200 MD Maastricht, The Netherlands. l.krabbendam@sp.unimaas.nl
Isusi
Pilar
P
Galdos
Paloma
P
Echevarria
Elena
E
Bilbao
José Ramón
JR
Martin-Pagola
Ainhoa
A
Papiol
Sergi
S
Castaño
Luis
L
Van Os
Jim
J
D000328:Adult; D000483:Alleles; D001288:Attention; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011930:Reaction Time / Q000235:genetics*; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012569:Schizotypal Personality Disorder / Q000175:diagnosis / Q000235:genetics; D014633:Valine / Q000235:genetics*
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine