A psychiatrie cross-disorder gene encoding arsenic methyltransferase alters basic cognitive processing speed

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2014-08-01

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en

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Abstract

Genetic variants in the AS3MT gene have been associated with the neuropsychiatric disorders schizophrenia, major depression, bipolar disorder, attention deficit hyperactivity disorder and autism spectrum disorder. One may hypothesize that this association of AS3MT with several psychiatrie disorders is due to a general detrimental effect on cognitive functioning or an effect on a more specific neuropsychological domain commonly impaired in the disorders. The aim of the current study was to distinguish between these two hypotheses. In adult ADHD and childhood ADHD cohorts and healthy controls (naduu=240 and nchildhood= 472), baseline reaction time, trail making, working memory and IQ were tested for association with AS3MT genotype. Furthermore, a voxel-based morphometry analysis of the whole brain was performed in a sample of healthy young adults (n=2346). Baseline reaction times showed a significant association with AS3MT genotype, with opposite effects in adults and children. In adulthood, carriers of the risk variant were found to have longer baseline reaction times (p=0.02), whereas in childhood they responded faster (p=0.03). Findings were observed in both patients and healthy comparison subjects. None of the scores for other tasks diff ered significantly between carriers and non-carriers of the risk variant, and there was no significant association of brain volume with AS3MT genotype. Individuals with the risk genotype showed a borderline significant (p=0.069) reduced white matter volume in frontal brain regions. On the neuropsychological level, our results suggest a domain specific, age-dependent effect of AS3MT genotype on processing speed. On the level of the brain our results remain inconclusive, so further studies are needed to identify the neural correlate of the observed effect of AS3MT genotype on processing speed.

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Faculteit der Sociale Wetenschappen