Aims:

We propose to carry out a study examining the neural substrate of an operationally and psychometrically-defined high risk (HR) or intermediate phenotype for the later development of schizophrenia spectrum disorders. This will recruit subjects from the ALSPAC birth cohort and apply structural MRI and voxel-based morphometry. The proposed HR phenotype comprises the combination of persistent (or recurrent) psychosis-like symptoms (PLIKS) between ages 12 and their current age (17), and evidence of stable cognitive deficits at age 8 and age 15. Thus the main aim is: to carry out MRI on a unique epidemiologically based sample of 30 high-risk non-prodromal, non-helpseeking, non-highly familial individuals and 30 matched controls in a nested case-control design within the cohort. Controls will be selected to have either, normal IQ and PLIKS, or, below average IQ but no PLIKS. Such a study will be a once-only opportunity to gather data prior to the peak age of risk. It is essentially a pilot study but will yield important results in its own right and will point the way for work in other modalities (eg spectroscopy and neurochemical imaging). A subsidiary aim is to explore the acceptability of this kind of research to participants in this cohort to offset future attrition.