New research on children with attention deficit/hyperactivity disorder has found a deficiency of a necessary brain chemical. Children with ADHD appear to have nearly 50 percent lower levels of an amino acid called tryptophan, a protein which helps in the production of dopamine, noradrenaline, and serotonin. It also is important for attention and learning.
Jessica Johansson of Orebro University in Sweden and her team set out to investigate whether children with ADHD show differences in the transport of the proteins tryptophan, tyrosine and alanine, since these amino acids are the precursors for brain chemicals which have already been implicated in the development of ADHD.
They analyzed connective tissue cells called fibroblasts from 14 boys ages 6 to 12, each of whom had ADHD. It turned out that the cells’ ability to transport tryptophan is lower in boys with ADHD than in other boys.
The finding could suggest greater biochemical disturbances in the brains of people with ADHD than previously realized, Ms. Johansson said. She commented, “This indicates that several signal substances are implicated in ADHD, and in the future this could pave the way for other drugs than those in use today.”
She explained that her work focuses on analyzing important signaling substances in the brain. Excessively low levels of these substances may lie behind the development of conditions such as ADHD.
The findings “probably mean that the brain produces less serotonin,” she said. “Thus far the focus has mainly been on the signal substances dopamine and noradrenaline in the medical treatment of ADHD. But if low levels of serotonin are also a contributing factor, other drugs may be necessary for successful treatment.”
Low serotonin could contribute to greater impulsivity, she added, which is a core symptom of ADHD. More investigation into serotonin in people with ADHD and disruptive behavior disorders is urgently needed, she believes.
The children in the ADHD group also had increased transport of the amino acid alanine in their fibroblast cells. It is unclear how this affects ADHD, the experts say, but they suggest it might influence the transport of other amino acids important for normal brain activity.
Interestingly, increased transport of alanine has also been found in children with autism. In a study of nine boys and two girls with autism, fibroblast samples showed significantly increased transport capacity for alanine. This increased transport of alanine across the cell membrane “may influence the transport of several other amino acids across the blood-brain barrier,” said the researchers, adding that, “the significance of the findings has to be further explored.”
No differences were seen in the action of the amino acid tyrosine in the samples from boys with ADHD, which the experts say “is difficult to explain,” given that tryptophan activity was different to that in boys without ADHD. However, they think it means that the change in tryptophan “could be linked to a more general alteration in cell membrane function in ADHD.” Similar changes in cell membranes have been seen in other psychiatric disorders such as schizophrenia and bipolar disorder.
Team leader Dr. Nikolaos Venizelos points out that dramatically reduced levels of the acetylcholine receptor were also seen in the boys with ADHD. This lack could cause problems with concentration and learning.
Drugs that improve acetylcholine levels already are available and currently are used in treating Alzheimer’s disease. Full details of the study appear in the journal Behavioral and Brain Functions.
Dr. Venizelos added, “I’m doing research on mental diseases and functional impairments at the cellular level. Many of these are assumed to be the consequence of excessively low levels of important signal substances in the brain, so cell biochemical analyses help us understand the processes that cause the changes.”
This study was limited by a small patient group which included only boys. But the team conclude, “Children with ADHD may have a decreased access of tryptophan and an elevated access of alanine in the brain.
“The decreased tryptophan availability in the brain might cause disturbances in the serotonergic neurotransmitter system, which secondarily might lead to changes in the catecholaminergic system [which covers dopamine activity].”
In this way, the new discoveries fit with previous findings that the genes identified as linked to ADHD include several that are linked with the catecholaminergic system.
Finally, the experts call for “a further and extended exploration concerning the disturbance of amino acid transport in children with ADHD.”
References
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191351/?tool=pubmed
Fernell, E. et al. Aberrant amino acid transport in fibroblasts from children with autism. Neuroscience Letters, March 12 2007, doi:10.1016/j.neulet.2007.03.004
Johansson, J. et al. Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study. Behavioral and Brain Functions, September 24 2011, doi:10.1186/1744-9081-7-40