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Jepma, M.; Deinum, J.; Asplund, C.L.; Rombouts, S.A.R.B.; Tamsma, J.T.; Tjeerdema, N.; ... ; Nieuwenhuis, S. (2011)

Neurocognitive Function in Dopamine-beta-Hydroxylase Deficiency

Article / Letter to editor
Dopamine-beta-hydroxylase (D beta H) deficiency is a rare genetic syndrome characterized by the complete absence of norepinephrine in the peripheral and the central nervous system. D beta H-deficient patients suffer from several physical symptoms, which can be treated successfully with L-threo-3,4-dihydroxyphenylserine, a synthetic precursor of norepinephrine. Informal clinical observations suggest that D beta H-deficient patients do not have obvious cognitive impairments, even when they are not medicated, which is remarkable given the important role of norepinephrine in normal neurocognitive function. This study provided the first systematic investigation of neurocognitive function in human D beta H deficiency. We tested 5 D beta H-deficient patients and 10 matched healthy control participants on a comprehensive cognitive task battery, and examined their pupil dynamics, brain structure, and the P3 component of the electroencephalogram. All participants were tested twice; the...Show moreDopamine-beta-hydroxylase (D beta H) deficiency is a rare genetic syndrome characterized by the complete absence of norepinephrine in the peripheral and the central nervous system. D beta H-deficient patients suffer from several physical symptoms, which can be treated successfully with L-threo-3,4-dihydroxyphenylserine, a synthetic precursor of norepinephrine. Informal clinical observations suggest that D beta H-deficient patients do not have obvious cognitive impairments, even when they are not medicated, which is remarkable given the important role of norepinephrine in normal neurocognitive function. This study provided the first systematic investigation of neurocognitive function in human D beta H deficiency. We tested 5 D beta H-deficient patients and 10 matched healthy control participants on a comprehensive cognitive task battery, and examined their pupil dynamics, brain structure, and the P3 component of the electroencephalogram. All participants were tested twice; the patients were tested once ON and once OFF medication. Magnetic resonance imaging scans of the brain revealed that the patients had a smaller total brain volume than the control group, which is in line with the recent hypothesis that norepinephrine has a neurotrophic effect. In addition, the patients showed an abnormally small or absent task-evoked pupil dilation. However, we found no substantial differences in cognitive performance or P3 amplitude between the patients and the control participants, with the exception of a temporal-attention deficit in the patients OFF medication. The largely spared neurocognitive function in D beta H-deficient patients suggests that other neuromodulators have taken over the function of norepinephrine in the brains of these patients. Neuropsychopharmacology (2011) 36, 1608-1619; doi:10.1038/npp.2011.42; published online 6 April 2011Show less
dopamine-beta-hydroxylase deficiency norepinephrine cognition brain DOPS l-threo-3,4-dihydroxyphenylserine l-dops coeruleus-norepinephrine system event-related potentials locus-coeruleus attentional blink working-memory noradrenergic modulation visuospatial attention emotional memory noradrenaline
All authors
Jepma, M.; Deinum, J.; Asplund, C.L.; Rombouts, S.A.R.B.; Tamsma, J.T.; Tjeerdema, N.; Spape, M.M.; Garland, E.M.; Robertson, D.; Lenders, J.W.M.; Nieuwenhuis, S.
Date
2011-07-31
Journal
Neuropsychopharmacology
Volume
36
Issue
8
Pages
1608 - 1619
DOI
doi:10.1038/npp.2011.42