title: Urinary neurotransmitters are selectively altered in children with obstructive sleep apnea and predict cognitive morbidity.
abstract: BACKGROUND
  Pediatric obstructive sleep apnea (OSA) is associated with cognitive dysfunction, suggesting altered neurotransmitter function. We explored overnight changes in neurotransmitters in the urine of children with and without OSA.
  
  
  METHODS
  Urine samples were collected from children with OSA and from control subjects before and after sleep studies. A neurocognitive battery assessing general cognitive ability (GCA) was administered to a subset of children with OSA. Samples were subjected to multiple enzyme-linked immunosorbent assays for 12 neurotransmitters, and adjusted for creatinine concentrations.
  
  
  RESULTS
  The study comprised 50 children with OSA and 20 control subjects. Of the children with OSA, 20 had normal GCA score (mean ± SD) (101.2 ± 14.5) and 16 had a reduced GCA score (87.3 ± 13.9; P &lt; .001). Overnight increases in epinephrine, norepinephrine, and γ-aminobutyric acid (GABA) levels emerged in children with OSA; taurine levels decreased. Using combinatorial approaches and cutoff values for overnight changes of these four neurotransmitters enabled prediction of OSA (area under the curve [AUC]: 0.923; P &lt; .0001). Furthermore, GABA and taurine alterations, as well as overnight reductions in phenylethylamine, were more prominent in children with OSA and low GCA than in children with OSA and normal GCA (P &lt; .001), and they reliably discriminated GCA status (AUC: 0.977; P &lt; .0001).
  
  
  CONCLUSIONS
  Pediatric OSA is associated with overnight increases in urinary concentrations of catecholamines indicative of heightened sympathetic outflow. Increases in GABA levels and decreases in taurine levels could underlie mechanisms of neuronal excitotoxicity and dysfunction. Combinatorial approaches using defined cutoffs in overnight changes in concentrations of selected neurotransmitters in urine may not only predict OSA but also the presence of cognitive deficits. Larger cohort studies appear warranted to confirm these findings.
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Leila
authors.initials: L
authors.lastname: Kheirandish-Gozal
authors.affiliation: NeuroScience, Inc, Osceola, WI.
authors.forename: Corena J T
authors.initials: CJT
authors.lastname: McManus
authors.affiliation: NeuroScience, Inc, Osceola, WI.
authors.forename: Gottfried H
authors.initials: GH
authors.lastname: Kellermann
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Arash
authors.initials: A
authors.lastname: Samiei
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL. Electronic address: dgozal@uchicago.edu.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000704:Analysis of Variance; D019540:Area Under Curve; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis / Q000652:urine*; D003404:Creatinine / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D018377:Neurotransmitter Agents / Q000652:urine*; D017286:Polysomnography; D012372:ROC Curve; D012680:Sensitivity and Specificity; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000652:urine*
chemical_list: D018377:Neurotransmitter Agents; D003404:Creatinine