Influence of the COMT Genotype on Working Memory and Brain Activity Changes During Development

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• 作者：Iroise Dumontheil^a ; ^{i.dumontheil@gmail.com"" rel=""nofollow} ; Chantal Roggeman^a ; Tim Ziermans^a ; Myriam Peyrard-Janvid^b ; Hans Matsson^b ; Juha Kere^b ; ^c ; ^d ; Torkel Klingberg^a
• 关键词：Child development ; functional magnetic resonance imaging (fMRI) ; genetics ; gray matter ; voxel-based morphometry (VBM) ; working memory
• 刊名：Biological Psychiatry
• 出版年：2011
• 出版时间：1 August 2011
• 年：2011
• 卷：70
• 期：3
• 页码：222-229
• 全文大小：1265 K

文摘

Background

The Valine158Methionine (Val158Met) polymorphism of the COMT gene leads to lower enzymatic activity and higher dopamine availability in Met carriers. The Met allele is associated with better performance and reduced prefrontal cortex activation during working memory (WM) tasks in adults. Dopaminergic system changes during adolescence may lead to a reduction of basal dopamine levels, potentially affecting Met allele benefits during development.

Methods

We investigated the association of COMT genotype with behavioral (n = 322) and magnetic resonance imaging data (n = 81–84) collected during performance of a visuospatial WM task and potential changes in these effects during development (reflected in age × genotype interactions). Data were collected from a cross-sectional and longitudinal typically developing sample of 6- to 20-year-olds.

Results

Visuospatial WM capacity exhibited an age × genotype interaction, with a benefit of the Met allele emerging after 10 years of age. There was a parallel age × genotype interaction on WM-related activation in the right inferior frontal gyrus and intraparietal sulcus (IPS), with increases in activation with age in the Val/Val group only. Main effects of COMT genotype were also observed in the IPS, with greater gray matter volumes bilaterally and greater right IPS activation in the Val/Val group compared with the Met carriers.

Conclusions

These results suggest that COMT genotype effects on WM brain activity and behavior are not static during development. The full developmental picture should be considered when trying to understand the impact of genetic polymorphisms on the mature cognition of healthy adult or psychiatric populations.