title: Multimodal neuroimaging studies and neurodevelopment and neurodegeneration hypotheses of schizophrenia.
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 spectrocopy] 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 disinihibition, 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 prefrotnal disinhibition would overstimulate the limbic system and the hippocampus would become overactivated, 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.
authors.affiliation: Dept of Psychiatry, Hospital 12 de Octubre, Edificio de Medicina Comunitaria, Avda de Córdoba, km 5.4, 28041, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Molina
authors.forename: Santiago
authors.initials: S
authors.lastname: Reig
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
authors.forename: Juan D.
authors.initials: JD
authors.lastname: Gispert
authors.forename: Javier
authors.initials: J
authors.lastname: Sanz
authors.forename: Fernando
authors.initials: F
authors.lastname: Sarramea
authors.forename: Javier
authors.initials: J
authors.lastname: Pascau
authors.forename: Carlos
authors.initials: C
authors.lastname: Benito
authors.forename: Raul
authors.initials: R
authors.lastname: Martínez-Lázaro
authors.forename: Rogelio
authors.initials: R
authors.lastname: Luque
authors.forename: María
authors.initials: M
authors.lastname: Aragües
authors.forename: Jose M.
authors.initials: JM
authors.lastname: Misiego
authors.forename: Ignacio López
authors.initials: IL
authors.lastname: Corral
authors.forename: Thomás
authors.initials: T
authors.lastname: Palomo