Kinetics of tyrosine transport and cognitive functioning in schizophrenia

Background: Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (V-max) across the cell membrane and an increased affinity (K-m) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction-a core feature of schizophrenia. Methods: Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters V-max and K-m were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. Results: Patients with low K-m (below the median) had poorer cognitive performance than patients with high K-m (above the median). V-max did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. Conclusions: Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low K-m and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons. (C) 2004 Elsevier B.V. All rights reserved.