Aberrant tyrosine transport across the fibroblast membrane in patients with schizophrenia--indications of maternal inheritance.
BACKGROUND
In previous studies of the present patients with schizophrenia, aberrant tyrosine transport across the fibroblast membrane was found. A low K(m), a kinetic factor indicating high affinity between tyrosine and the binding site at the cell membrane, was found to be associated with poor cognitive functions in patients. The present study aimed at investigating possible relationships between patients with schizophrenia and their first-degree relatives in aberrant tyrosine transport indicating that it may be a biological marker for the genetic susceptibility.


METHODS
Thirty-three parents, 13 fathers and 20 mothers, from 23 families with a schizophrenic patient agreed to enter the study. They underwent skin biopsies for fibroblast cultivation, neuropsychological and psychiatric investigations and were classified as family history positive or negative. Tyrosine transport kinetics (K(m) and V(max)) were calculated from in vitro trials of gradients of extracellular tyrosine concentrations in fibroblast cultures.


RESULTS
An association between patients with schizophrenia and their mothers were found for a low K(m) indicating maternal inheritance. Mothers displaying a low K(m) performed worse on the neuropsychological tests compared to mothers with normal K(m). Corresponding relationships between a low K(m) and neurocognitive dysfunction had previously been found for the patients.


CONCLUSIONS
An aberrant tyrosine transport across plasma membrane may constitute a biological marker for an endophenotype within the schizophrenia spectrum with low cognitive functioning. A plausible mode for genetic transmission is maternal inheritance.
Flyckt
Lena
L
Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden. lena.flyckt@ki.se
Edman
Gunnar
G
Venizelos
Nikolaos
N
Borg
Kristian
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000209:etiology; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010290:Parents; D012559:Schizophrenia / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism*; D055815:Young Adult
D014443:Tyrosine