A preliminary report on dopamine system reactivity in PKU: acute effects of haloperidol on neuropsychological, physiological, and neuroendocrine functions.
BACKGROUND
Classic phenylketonuria (PKU) is due to an inborn error of metabolism resulting in an inability to metabolize the amino acid phenylalanine. To avoid mental retardation, affected individuals observe a phenylalanine-restricted diet. When dietary control is poor, deficits in prefrontally mediated cognitive functions have been observed. It has been suggested that these deficits are due to disruptions in the mesocortical dopamine system that projects to the prefrontal cortex.


METHODS
In this study, dopamine system reactivity was examined in individuals with PKU, relative to age-matched controls, using the non-specific DA antagonist haloperidol, in a repeated measures placebo-controlled design. Outcome variables included neuroendocrine, physiological, and cognitive measures.


RESULTS
Regardless of drug condition, PKU participants differed from control participants in their blood phenylalanine and tyrosine levels, and in their times to complete measures of attention and working memory. Also, relative to placebo, haloperidol influenced several variables irrespective of group status, including serum prolactin secretion, times to complete attention and working memory tasks, and accuracy of working memory performance. An interaction between group and drug condition was observed for the digit span task, where PKU participants exhibited greater relative impairments on haloperidol. When composite indices of impairment were derived, PKU participants demonstrated selective disruption in executive function on haloperidol relative to control subjects.


CONCLUSIONS
Findings are consistent with the presence of frontostriatal dysfunction in PKU but are less consistent with the notion that PFC dopamine function is specifically affected.
Luciana
Monica
M
Department of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN 55455, USA. lucia003@tc.umn.edu
Hanson
Karen L
KL
Whitley
Chester B
CB
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000378:metabolism* / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D011388:Prolactin / Q000378:metabolism; D013647:Task Performance and Analysis; D014443:Tyrosine / Q000097:blood
D018492:Dopamine Antagonists; D014443:Tyrosine; D010649:Phenylalanine; D011388:Prolactin; D006220:Haloperidol; D004298:Dopamine