Cognitive trait and state markers in subjects at genetic high risk

Abstract

Background

Prospective studies of young individuals at high genetic risk of schizophrenia allow investigation of whether any neurodevelopmental abnormalities usefully predict the development of the disorder.

Method

163 high risk subjects with an initial mean age of 21 years were recruited as they had at least two relatives with schizophrenia. Together with 36 control subjects, they were examined at baseline (with developmental, clinical, neuropsychological and structural/functional MRI measures) and at 18 month intervals thereafter. Comparisons were made between those who developed schizophrenia, well controls, a well high risk group and those of the high risk sample with partial or isolated psychotic symptoms.

Results

21 high risk subjects developed schizophrenia within an average time of two and a half years. A much larger number have shown isolated or partial psychotic symptoms and the whole high risk sample differed from controls on several variables. Those who developed schizophrenia differed from those with psychotic symptoms who did not on several measures including: interview and self-report measures of schizotypy, the AVLT1-5, and fMRI-BOLD responses on three separate tasks.

Conclusions

Schizophrenia is a disorder which has its origins very early in life, but develops over years. Its mode of inheritance affects many more individuals than will develop the illness and partial impairment can be found in them. Highly significant predictors of the development of schizophrenia are detectable years before onset.