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 (Vmax) across the cell membrane and an increased affinity (Km) 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 Vmax and Km 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 Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax 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 Km 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.
Wiesel
Frits-Axel
FA
Department of Neuroscience, Psychiatry, Ulleråker, Uppsala University Hospital, Uppsala SE-750 17, Sweden. Frits-Axel.Wiesel@neuro.uu.se
Edman
Gunnar
G
Flyckt
Lena
L
Eriksson
Asa
A
Nyman
Håkan
H
Venizelos
Nikolaos
N
Bjerkenstedt
Lars
L
D000293:Adolescent; D000328:Adult; D001692:Biological Transport; D001706:Biopsy; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D012867:Skin / Q000473:pathology; D014443:Tyrosine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014443:Tyrosine