title: Neurocognitive function in dopamine-β-hydroxylase deficiency.
abstract: Dopamine-β-hydroxylase (DβH) deficiency is a rare genetic syndrome characterized by the complete absence of norepinephrine in the peripheral and the central nervous system. DβH-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 DβH-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 DβH deficiency. We tested 5 DβH-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 DβH-deficient patients suggests that other neuromodulators have taken over the function of norepinephrine in the brains of these patients.
authors.affiliation: Leiden University, Institute of Psychology, Leiden, The Netherlands. mjepma@fsw.leidenuniv.nl
authors.forename: Marieke
authors.initials: M
authors.lastname: Jepma
authors.forename: Jaap
authors.initials: J
authors.lastname: Deinum
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Asplund
authors.forename: Serge Arb
authors.initials: SA
authors.lastname: Rombouts
authors.forename: Jouke T
authors.initials: JT
authors.lastname: Tamsma
authors.forename: Nathanja
authors.initials: N
authors.lastname: Tjeerdema
authors.forename: Michiel M
authors.initials: MM
authors.lastname: Spapé
authors.forename: Emily M
authors.initials: EM
authors.lastname: Garland
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Jacques Wm
authors.initials: JW
authors.lastname: Lenders
authors.forename: Sander
authors.initials: S
authors.lastname: Nieuwenhuis
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology; D001342:Autonomic Nervous System Diseases / Q000201:enzymology* / Q000503:physiopathology / Q000523:psychology*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000201:enzymology* / Q000503:physiopathology / Q000523:psychology*; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D009638:Norepinephrine / Q000172:deficiency; D010775:Photic Stimulation / Q000379:methods; D011597:Psychomotor Performance / Q000502:physiology*; D055815:Young Adult
chemical_list: D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine