Changes in Gray Matter Density Signal Schizophrenia Risk

EDINBURGH, Scotland, Dec. 7 -- For a person at high risk for schizophrenia, a reduction in gray matter in the temporal lobes over time suggests a high likelihood that psychosis will develop, reported investigators here.

In a study of 65 young men and women with a family history of schizophrenia, those with changes over time in the inferior temporal gyrus had a 10-fold greater risk for developing schizophrenia than the cohort as a whole, reported Dominic E. Job, M.D., of the University of Edinburgh, and colleagues.

"Changes in gray 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." the investigators wrote in the Dec. 7 issue of the open-access journal BMC Medicine.

The investigators studied a cohort of 34 men and 31 women, age 21.4 + 2.7, who took part in the Edinburgh High Risk study. Investigators in the prospective study have examined over 10 years the mental state and brain structure of more than 150 young men and women with a history of familial schizophrenia.

Twenty-one members of the total of 150 developed schizophrenia during the study, and 60 others have had transient, isolated, or partial psychotic symptoms on at least one occasion but have not developed schizophrenia. Most with these symptoms are now past the maximum age for risk, the authors noted.

In the current study, they looked at changes over time in 65 members of the Edinburgh High Risk cohort.

Fifty-seven of the 65 cohort members remained well, but eight went on to develop schizophrenia an average of 2.3 + 1 years after their first scan. The diagnosis of schizophrenia was made using the Present State Examination/CATEGO-5 program, and ICD-10 criteria.

The authors used voxel-based morphometry to compare the scans, looking for changes in temporal lobe gray density.

They found that the best predictive value came from changes in the inferior temporal gyrus, which yielded a 60% positive predictive value. In other words, 60% of the patients who had reductions in gray matter density above the threshold will go on to develop schizophrenia.

The negative predictive value was 92%, indicating that 92% of those whose gray matter changes fell below the threshold would not go on to develop schizophrenia.

"The likelihood ratio for a positive test (10.69) tells us that a subject with a positive test, i.e. a score above the threshold, is 10 times more likely to develop schizophrenia than a subject with a negative test," the authors wrote. "The negative likelihood ratio for this test (of 0.65) tells us that a subject who tests negative is nearly twice as likely to stay well as a subject with a positive test."

Their results suggest that MRI studies of changes in gray matter density can be combined with clinical and cognitive testing to provide more accurate positive predictive testing for schizophrenia risk.

"Although a sensitive issue, an accurate predictive test for (familial) schizophrenia could have substantial utility in assessing the possibilities for preventing the onset of this most disabling of disorders," they concluded.

The study was funded by a program grant from the Medical Research Council of Great Britain. The authors had no relevant financial disclosures.

The study is available free of charge at http://www.biomedcentral.com/bmcmed/ .