Abstract
The interpretation of the huge number of results in schizophrenia research using neuroimaging is uncertain. However, the simultaneous use of complimentary data obtained with these techniques may yield more relevant information in this regard. In this paper, we present a series of studies performed by our group in two schizophrenic samples with the use of structural (magnetic resonance imaging (MRI)), functional [glucose positron emission tomography (PET) and N -acetyl-aspartate (NAA) magnetic resonance spectroscopy] and neurophysiological techniques (the P300 event-related potential). Transversal and longitudinal measurements were performed. The integrated vision of the results so obtained allows us to propose the hypothesis of a neurodevelopmentally determined state of prefrontal disinhibition, in which the degree of atrophy would directly relate to the metabolic rate. This state would already be present in the first stages of illness and could have neurotoxic consequences in the long term. This would explain the findings of an association between sulcal cerebrospinal fluid (CSF) and illness duration and decreased NAA levels in chronic but not in recent-onset cases. The prefrontal disinhibition would over stimulate the limbic system and the hippocampus would become over activated, the metabolic rate at this level being inversely related to P300 amplitude. Clozapine showed a more selective and intense action on that hyperactive metabolic tone than haloperidol.