Prefrontal atrophy in first episodes of schizophrenia associated with limbic metabolic hyperactivity

Reduced volume and activity of the prefrontal (PF) cortical gray matter (GM) and hippocampal hypermetabolism are repeated findings in schizophrenia. There is still an information deficit about the significance of reduction of PF GM in schizophrenia, and a simultaneous study of PF anatomy and activity and limbic metabolism can contribute to fill that deficit. In order to do so, we used positron emission tomography (PET) with 18-fluoro-deoxyy-glucose (FDG) during an attention task and magnetic resonance imaging (MRI) to study a sample of first episodes of pscyhosis. We included 21 first episodes (FE) of psychosis and 16 healthy controls. A diagnosis of schizophrenia was confirmed in the follow-up in eleven of these patients and ruled out in the remaining 10 cases. Volumes of PF GM were determined and also activity in the same region and in the hippocampus. Residual GM was estimated in the PF region as a quantitative measurement of the degree of atrophy in each individual, using age and intracranial volume data from a set of 45 healthy controls and linear regression.Patients with schizophrenia had lower PF metabolic activation and greater hippocampal activity than controls. FE patients without schizophrenia were no different in any parameter as compared to controls. Patients with schizophrenia presented an inverse and significant association between GM deficit and hippocampal activity that was not observed in controls or in patients without schizophrenia. The same association was previously described by our group using PET in the resting state in recent-onset and chronic patients with schizophrenia. These findings support a loss in PF inhibitory capacity as a possible link between anatomical and functional alterations in schizophrenia.