Schizophrenia and the frontal brain: a quantitative review.

Structural and physiological frontal brain system deficits in patients with schizophrenia are reviewed quantitatively. We report effect sizes from studies since 1980 that used structural (CT, MRI), and functional (PET) neuroimaging methods. We found both literatures to be distinguished by heterogeneity whereby most patients show normative frontal function and structure, a minority shows diminished values and some patients demonstrate augmented function and structure rather than deficit. The average magnitude of difference between patients and controls is generally too modest to support the idea that frontal brain dysfunction is a necessary component of schizophrenia. This modesty is most apparent in average effects obtained for frontal brain volume (M = -.36), left frontal brain volume (M = -.16), frontal resting metabolism, and blood flow (M = -.64). Effect sizes of this magnitude imply that schizophrenia and control distributions overlap by as much as 88% and no less than about 60% on frontal brain measures. It is only when behavioral measures are employed as activation tasks during frontal blood flow and metabolism studies, that average effect sizes rise in magnitude to indicate patient-control distribution overlaps that are less than 50%. Overall, the findings are hard to incorporate within single disease models that propose major involvement of the frontal system, at least at the degree of resolution obtained with current imaging technology.