Association study of a functional catechol-O-methyltransferase-gene polymorphism and cognitive function in healthy females

Tsai, Shih‐Jen; Yu, Younger W.‐Y.; Chen, Tai Jui; Chen, Jen Yeu; Liou, Ying‐Jay; Chen, Ming Chao; Chen, Hong

doi:10.1016/s0304-3940(02)01396-4

Cited by 133 publications

(91 citation statements)

References 18 publications

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“…Except for the Tsai et al study 104 (which studied Han Chinese female nursing students aged between 19 and 21 years), the mean age of subjects in previous studies 52,59,[101][102][103]105,106,108 are substantially older than ours. Age-related loss in frontal lobe dopamine function has been repeatedly demonstrated in post-mortem as well as in vivo neuroimaging studies (eg Rinne, 109 de Keyser et al, 110 Suhara et al, 111 Kaasinen et al 112 and Volkow et al 113 ).…”

Section: Discussioncontrasting

confidence: 63%

“…59 In another study, healthy volunteers with the valine allele committed significantly more WCST perseverative errors than those with methionine allele. 101 The effects of V 158 M COMT polymorphism appear to extend beyond WCST performance, and have been implicated in other measures of prefrontal neurocognitive functions (such as N-back task 102 and prefrontal P300 amplitude and latency 103,104 ), and in mediating other cognitive domains (such as processing speed and attention 105 and 'cognitive stability and flexibility' 106 ). All these studies have found an association between the valine allele and poorer cognitive performance, and postulate that the underlying mechanism may be related to lower prefrontal dopamine levels arising from higher dopamine catabolism mediated by the valine allele.…”

Section: Discussionmentioning

confidence: 99%

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Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

et al. 2005

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The catechol-O-methyl transferase (COMT) gene is considered a leading schizophrenia candidate gene. Although its role in increasing schizophrenia susceptibility has been conflicting, recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia. V 158 M COMT genotype was obtained on 159 schizophrenia patients and 84 healthy controls. The effects of COMT genotype on four measures of working memory/ executive functions (Wisconsin Card Sorting, digit span backward, Trail Making and N-back tests) and on MRI frontal brain volumes were examined. Genotype distributions were not significantly different between patients and controls. There were no significant genotype or genotype-by-group effects on any working memory/executive function measures. No genotype or genotype-by-diagnosis interaction effects were found with MRI frontal lobe volumes. Randomization analyses using [ 15 O]H 2 O positron emission tomography (PET) cerebral blood flow data found Val/Val patients had higher frontal lobe activation than Met/Met patients while performing the one-back task. Overall, these findings do not support a major role for COMT in increasing susceptibility for schizophrenia or in mediating frontal lobe function. Age-related changes and phenotypic heterogeneity of schizophrenia may influence the complex relationships between COMT genotype and cognition.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

et al. 2005

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“…Two previous reports focused on electrophysiological measures as a function of COMT genotype. Tsai et al (2003) examined healthy female subjects and found that Met allele carriers had significantly reduced P300 latencies in a genedose-dependent manner. Gallinat et al (2003), on the other hand, investigated schizophrenic patients and healthy controls by means of an auditory oddball paradigm without finding an effect of COMT genotype on P300 latencies.…”

Section: Discussionmentioning

confidence: 99%

Impact of Catechol-O-Methyltransferase on Prefrontal Brain Functioning in Schizophrenia Spectrum Disorders

Ehlis

Reif

Herrmann

et al. 2006

Neuropsychopharmacol

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The enzyme catechol-O-methyltransferase (COMT) has attracted increasing interest regarding a genetic disposition towards schizophrenias and as a modulator of prefrontal brain function. A common SNP in the COMT gene causes a Val to Met transition at AA158/AA108 (Val158Met), resulting in reduced COMT activity in Met allele carriers. An impact of COMT genotype on cognition has been well established; however, the exact nature of this influence has yet to be elucidated. The aim of this study was to determine whether COMT genotype affects an electrophysiological marker of prefrontal activation and neuropsychological frontal lobe measures in schizophrenia. To this end, 56 acutely psychotic in-patients with schizophrenia spectrum disorders were investigated. Patients with the COMT 1947AA (Met/Met) genotype (n ¼ 13) were compared to a carefully matched sample of patients with a G1947A (Val/Met) genotype (n ¼ 15); matching criteria included patients' age, handedness, gender distribution, diagnosis, and medication status. A small group of six homozygous Val allele carriers was additionally included to allow an assessment of possible gene-dosage effects. P300 amplitudes and latencies, as well as an electrophysiological marker of prefrontal brain function (NoGo-Anteriorization/NGA) and neuropsychological measures (Stroop Test, Verbal Fluency, Trail Making Test) were regarded. Homozygous Met allele carriers had significantly increased NGA values and fronto-central Nogo amplitudes compared to patients with at least one Val allele. They also tended to perform better in the Stroop task, as compared to the matched group of Val/Met patients. These results indicate that COMT genotype exerts a strong impact on prefrontal functioning and executive control in schizophrenia spectrum disorders.

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“…4,[7][8][9] However, other studies have failed to find an association between Met allele frequency and WCST performance. 10,11 These discrepancies may reflect differences in ethnicity or gender distribution between samples. [12][13][14] They might also reflect publication bias such as a tendency to publish positive but not negative findings from small, underpowered association studies.…”

Section: Introductionmentioning

confidence: 99%

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

et al. 2007

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The catechol-O-methyltransferase (COMT) Val 158 Met polymorphism is hypothesized to affect executive function in patient and control populations. Studies inconsistently report better performance on the Wisconsin Card Sort Test (WCST) in individuals with one or more Met alleles. We conducted a meta-analysis of studies published until August 2006 that reported WCST perseverative errors from healthy volunteers or patients with schizophrenia-spectrum disorders. Twelve studies met inclusion criteria (total n = 1910) providing 10 samples each of patients and controls. In healthy controls, individuals with the Met/Met genotype performed better than those with the Val/Val genotype (d = 0.29; 95% confidence interval (CI) 0.02-0.55; P = 0.03), but this was not supported in the patient sample (d = À0.07; 95% CI À0.40 to 0.26; P = 0.68). Post hoc analyses suggested that Val and Met alleles are codominant in their effects on cognition. Effect size was greater in studies published at an earlier date and may also be larger in non-Caucasian samples. Gender did not affect the results. There was no evidence of publication bias. We conclude that there is small but significant relationship between Val 158 Met genotype and executive function in healthy individuals but not in schizophrenia.

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Association study of a functional catechol-O-methyltransferase-gene polymorphism and cognitive function in healthy females

Cited by 133 publications

References 18 publications

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

Impact of Catechol-O-Methyltransferase on Prefrontal Brain Functioning in Schizophrenia Spectrum Disorders

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

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