Support for limited brain availability of tyrosine in patients with schizophrenia

Several mechanisms have been suggested to account for altered dopaminergic neurotransmission in schizophrenia. The brain is the only organ for which amino-acid transport is limited and competition for transport over the blood-brain barrier (BBB) occurs at physiological plasma concentrations. One line of research suggests that patients with schizophrenia have altered brain levels of the essential amino acid tyrosine, the precursor for the synthesis of dopamine. The most common hypothesis is that less tyrosine is available because of competition with elevated levels of other amino acids. By consequence, the synthesis of dopamine in the brain will decrease. In contrast, another line of evidence suggests a change in the affinity for one of the transport proteins. A limitation of this research has been that the systems for amino-acid transport across the BBB have not been fully characterized at a molecular or functional level. The L system is the major system for transport of tyrosine across cell membranes including the BBB. The A system is also involved in this transport. Earlier in-vitro studies using fibroblasts have demonstrated a normal L system in schizophrenia but nevertheless reduced tyrosine transport. The combination of molecular research, fibroblast techniques, and brain imaging provides a new basis for clinical research on the role of amino-acid membrane transport in schizophrenia.