Consequences of Variations in Genes that affect Dopamine in Prefrontal Cortex
1 Department of Psychiatry, University of British Columbia, 2 BC Children's Hospital, Vancouver, Canada
Address correspondence to Adele Diamond, Canada Research Chair Professor of Developmental Cognitive Neuroscience, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada. Email: adele.diamond{at}ubc.ca.
Patricia Goldman-Rakic played a groundbreaking role in investigating the cognitive functions subserved by dorsolateral prefrontal cortex and the key role of dopamine in that. The work discussed here builds on that including: 1) Studies of children predicted to have lower levels of prefrontal dopamine but otherwise basically normal brains (children treated for phenylketonuria [PKU]). Those studies changed medical guidelines, improving the children's lives. 2) Studies of visual impairments (in contrast sensitivity and motion perception) in PKU children due to reduced retinal dopamine and due to excessive phenylalanine during the first postnatal weeks. Those studies, too, changed medical guidelines. 3) Studies of working memory and inhibitory control differences in typically developing children due to differences in catechol-O-methyltransferase (COMT) genotype, which selectively affect prefrontal dopamine levels. 4) Studies of gender differences in the effect of COMT genotype on cognitive performance in older adults. 5) A hypothesis about fundamental differences between attention deficit hyperactivity disorder (ADHD) that includes hyperactivity and ADHD of the inattentive type. Those disorders are hypothesized to differ in the affected neural system, underlying genetics, responsiveness to medication, comorbidities, and cognitive and behavioral profiles. These sound quite disparate but they all grew systematically out the base laid down by Patricia Goldman-Rakic.
Key Words: attention deficit hyperactivity disorder • cognitive control • catechol-o-methyltransferase • DAT1 • DRD4 • executive function • inhibition • phenylalanine hydroxylase • phenylketonuria • visual contrast sensitivity • working memory
Funding to pay the Open Access publication charges for this article was provided by NIH R01 grant #DA19685-16A2.
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