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Cited by 717

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU

Diamond, Adele, Prevor, Meredith B., Callender, Glenda, Druin, Donald P.·1997·Monographs of the Society for Research in Child Development
DOI 10.2307/1166208
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Abstract

To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed.

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Metadata

Authors
Diamond, A., Prevor, M. B., Callender, G., & Druin, D. P.
Venue
Monographs of the Society for Research in Child Development
Publisher
Oxford University Press (OUP)
Published
1997
Volume
62
Issue
4
Pages
i
ISSN
0037-976X (ISSN-L)
DOI
10.2307/1166208
OpenAlex
W2014883692
Cited by
717
References
11
FWCI
7.23
Type
journal article
Language
en
Open access
closed

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