Abstract
BackgroundThe 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.MethodsFibroblast 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 (Vmax) and affinity constant (Km) were determined. Any difference between the two groups was analyzed by Student's unpaired t-test or the Mann Whitney U test.ResultsThe ADHD group had significantly decreased Vmax (p = 0.039) and Km (increased affinity) (p = 0.010) of tryptophan transport in comparison to controls. They also had a significantly higher Vmaxof 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.ConclusionsTryptophan 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.
Highlights
The catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD)
When using the fibroblast cell model, previous findings by our group [23,24,25,26,27,28,29] and others [30] have shown a disturbed membrane transport of tyrosine in a number of psychiatric disorders, such as schizophrenia, autism and bipolar disorder, in a previous study by our group, we found that children with autism had an increased transport capacity of alanine across cell membranes [24]
The aim of this study was to investigate whether children with ADHD have changes in the transport of tyrosine and/or tryptophan, since these amino acids are the precursors for the neurotransmitters implicated in the pathophysiology of ADHD
Summary
The catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). 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. The aim of this study was to explore whether children with ADHD may have disturbed amino acid transport. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a prevalence in children of about 5-7% worldwide [1,2]. It is clinically characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity that affect cognitive, behavioural, emotional and social functioning and symptoms may persist into adulthood [1,3,4]. A recent study shows that children with ADHD have an increased rate of large copy number variants (CNVs) especially at chromosome 16 [7], which further support ADHD as a genetic disorder
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