Open Access Open Badges Research article

Grey matter changes can improve the prediction of schizophrenia in subjects at high risk

Dominic E Job*, Heather C Whalley, Andrew M McIntosh, David GC Owens, Eve C Johnstone and Stephen M Lawrie

Author affiliations

Division of Psychiatry, School of Molecular and Clinical Medicine, The University of Edinburgh, The Royal Edinburgh Hospital, Morningside Park, Edinburgh, Scotland, EH10 5HF, UK

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Citation and License

BMC Medicine 2006, 4:29  doi:10.1186/1741-7015-4-29

Published: 7 December 2006



We hypothesised that subjects at familial high risk of developing schizophrenia would have a reduction over time in grey matter, particularly in the temporal lobes, and that this reduction may predict schizophrenia better than clinical measurements.


We analysed magnetic resonance images of 65 high-risk subjects from the Edinburgh High Risk Study sample who had two scans a mean of 1.52 years apart. Eight of these 65 subjects went on to develop schizophrenia an average of 2.3 years after their first scan.


Changes over time in the inferior temporal gyrus gave a 60% positive predictive value (likelihood ratio >10) of developing schizophrenia compared to the overall 13% risk in the cohort as a whole.


Changes in grey matter could be used as part of a predictive test for schizophrenia in people at enhanced risk for familial reasons, particularly for positive predictive power, in combination with other clinical and cognitive predictive measures, several of which are strong negative predictors. However, because of the limited number of subjects, this test requires independent replication to confirm its validity.