What does the Edinburgh high-risk study tell us about schizophrenia?

The Edinburgh High Risk Study concerns 162 young people aged 16 to 25 at ascertainment who have at least two close relatives with schizophrenia. They are compared with two control groups (1) of age-matched well subjects and (2) of age-matched subjects with first schizophrenic episodes. The interim results show that schizophrenia has developed in 10 high-risk subjects and no controls and that all categories of psychopathology are more marked in the high-risk subjects. Psychopathology shows no relationships with measures of genetic liability. Neuropsychological measures are most impaired in the individuals with first-episode schizophrenia, with high-risk subjects performing better and well controls better still. The greater the genetic liability of the high-risk subjects, the poorer the neuropsychological performance. Neuropsychological impairments occurred in more high-risk subjects than are expected to develop schizophrenia. Structural brain scans show significant differences between those with first-episode schizophrenia, high-risk subjects, and well controls. Brain structure is related to genetic liability in that high-risk subjects with higher genetic liability have smaller right and left prefrontal lobes and smaller right and left thalami. In those high-risk subjects with two scans, there was a significantly greater reduction in temporal lobe size in those with psychotic symptoms than in those without. It is suggested that in high-risk subjects, the change from vulnerability to psychosis may be preceded by reduction in size and deteriorating function of the temporal lobe. Copyright 2002 Wiley-Liss, Inc.