title: Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study.
abstract: BACKGROUND
  The catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The amino acid tyrosine is the precursor for synthesis of the catecholamines dopamine and norepinephrine, while tryptophan is the precursor of serotonin. A disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other psychiatric disorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim of this study was to explore whether children with ADHD may have disturbed amino acid transport.
  
  
  METHODS
  Fibroblast cells were cultured from skin biopsies obtained from 14 boys diagnosed with ADHD and from 13 matching boys without a diagnosis of a developmental disorder. Transport of the amino acids tyrosine, tryptophan and alanine across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (V(max)) and affinity constant (K(m)) were determined. Any difference between the two groups was analyzed by Student's unpaired t-test or the Mann Whitney U test.
  
  
  RESULTS
  The ADHD group had significantly decreased V(max) (p = 0.039) and K(m) (increased affinity) (p = 0.010) of tryptophan transport in comparison to controls. They also had a significantly higher V(max)of alanine transport (p = 0.031), but the Km of alanine transport did not differ significantly. There were no significant differences in any of the kinetic parameters regarding tyrosine transport in fibroblasts for the ADHD group.
  
  
  CONCLUSIONS
  Tryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB). Hence, a decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB in the ADHD group. This could lead to deficient serotonin access in the brain that might cause disturbances in both the serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected. The physiological importance of an elevated transport capacity of alanine to the brain is not known to date.
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, 701 82 Örebro, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Johansson
authors.forename: Magnus
authors.initials: M
authors.lastname: Landgren
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Fernell
authors.forename: Ravi
authors.initials: R
authors.lastname: Vumma
authors.forename: Arne
authors.initials: A
authors.lastname: Åhlin
authors.forename: Lars
authors.initials: L
authors.lastname: Bjerkenstedt
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Venizelos
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism*; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D001812:Blood-Brain Barrier / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D021381:Protein Transport / Q000235:genetics; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism*
chemical_list: D014364:Tryptophan; D000409:Alanine