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Lack of association between COMT and working memory in a population-based cohort of healthy young adults.

ABSTRACT: The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene is an important regulator of dopamine in the prefrontal cortex, an area critical to working memory. Working memory deficits are present in several psychiatric disorders, and there is wide variation in working memory capacity in the normal population. Association studies of COMT and working memory in healthy volunteers have yielded inconsistent results, possibly because of small sample sizes. Here we examine COMT in relation to N-Back working memory task performance in a large population-based cohort of young adults. We predicted individuals with one or two copies of the Met allele would perform better, and that this relationship would be more evident in males than females. Participants (N=1857-2659) tested at 18 years of age, were enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). We used multiple regression to examine effects of sex and COMT genotype on N-Back hits, false positives, discriminability (d'), and reaction time while controlling for important covariates. COMT genotype did not predict hits or d'. There was a nominally significant interaction between COMT and sex on false positives, but this was not in the predicted direction, and was not significant after controlling for covariates. COMT genotype was not related to working memory in this large population-based cohort. It is possible COMT is not meaningfully associated with working memory in healthy young adults, or that COMT effects are detectable only in assessments reflecting neural processes underlying cognition, such as fMRI, rather than in behavioral performance.

SUBMITTER: Wardle MC

PROVIDER: S-EPMC3656369 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Lack of association between COMT and working memory in a population-based cohort of healthy young adults.

Wardle Margaret C MC de Wit Harriet H Penton-Voak Ian I Lewis Glyn G Munafò Marcus R MR

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20130121 7

The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene is an important regulator of dopamine in the prefrontal cortex, an area critical to working memory. Working memory deficits are present in several psychiatric disorders, and there is wide variation in working memory capacity in the normal population. Association studies of COMT and working memory in healthy volunteers have yielded inconsistent results, possibly because of small sample sizes. Here we examine COMT in relati ...[more]

PMID: 23337869

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Project description:AimsThe dopamine- and cAMP-regulated phosphoprotein (DARPP-32), which is encoded by the PPP1R1B gene, plays a converging regulatory role in the central nervous system by mediating the actions of dopamine, serotonin, and glutamate. Previous studies have demonstrated that variations in genes related to the dopamine system influence working memory. The present study thus investigated whether polymorphisms in PPP1R1B gene were associated with working memory.Materials and methodsA sample of 124 healthy Han Chinese were genotyped for three single nucleotide polymorphisms of PPP1R1B gene, namely rs12601930C/T, rs879606A/G, and rs3764352A/G, using polymerase chain reaction and restriction fragment length polymorphism analysis. Working memory performance was assessed using the Wisconsin Card Sorting Test (WCST).ResultsSignificant differences were observed in the Total Correct (TC), Total Errors (TE), and Conceptual Level Responses (CLR) scores of the WCST among the three rs12601930C/T genotypes (p = 0.044, 0.044, and 0.047, respectively); in TC, TE, Non-Perseverative Errors (NPE), and CLR scores between participants with the CC and (CT + TT) rs12601930C/T polymorphism genotypes (p = 0.032, 0.032, 0.019, and 0.029, respectively); in TC, TE, Perseverative Errors (PE), NPE, and CLR scores between participants with the (CT + CC) and TT rs12601930C/T polymorphism genotypes (p = 0.001, 0.001, 0.011, 0.004, and 0.001, respectively); and in NPE and CLR scores between participants with the GG and (AG + AA) genotypes of the rs3764352A/G polymorphism (p = 0.011 and 0.010). Furthermore, for males only, there were significant differences in TC, TE, PE, NPE, and CLR scores among the rs12601930C/T genotypes (p = 0.020, 0.020, 0.037, 0.029, and 0.014, respectively) and NPE and CLR scores among the rs3764352 genotypes (p = 0.045 and 0.042).ConclusionPPP1R1B gene polymorphisms rs12601930C/T and rs3764352A/G might be associated with working memory assessed by the WCST in healthy Chinese adults, especially among males.

Project description:ObjectiveTo identify an optimal lifestyle profile to protect against memory loss in older individuals.DesignPopulation based, prospective cohort study.SettingParticipants from areas representative of the north, south, and west of China.ParticipantsIndividuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009.Main outcome measuresParticipants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample.Results29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52).ConclusionA healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline.Trial registrationClinicalTrials.gov NCT03653156.

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Lack of association between COMT and working memory in a population-based cohort of healthy young adults.

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Lack of association between COMT and working memory in a population-based cohort of healthy young adults.

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