RESUMEN
INTRODUCTION: Clinical, neuropsychological and functional neuroimaging studies in schizophrenia suggest impaired frontal lobe function, especially of the dorsolateral prefrontal region (DLPFR). This dysfunction has in particular been associated with negative or "deficit" symptoms. Despite these findings, morphological studies have failed to show consistent structural abnormalities in the frontal lobe. This may be because existing techniques are not sensitive enough to detect structural abnormalities or that dysfunction in the frontal lobe is caused by lesions elsewhere. We used volume-localised proton magnetic resonance spectroscopy (1H-MRS) to measure N-acetylaspartate (NAA), a neuronal marker, to evaluate the neuronal integrity of the dorsolateral prefrontal region in schizophrenic patients with persistent negative symptoms and in healthy comparison subjects. METHOD: Twenty-five patients who fulfilled DSM-IV criteria for schizophrenia and met the criteria for the Deficit syndrome were compared to 26 healthy controls matched for age and gender. Bilateral proton MR spectra were collected from a 2-cm(3) volume in the dorsolateral prefrontal region and the absolute concentrations of N-acetylaspartate, choline (Cho) and creatine+phosphocreatine (Cr+PCr) were measured. RESULTS: There was a significant negative correlation between severity of symptoms and NAA concentration in the schizophrenic patients. This was more marked for positive symptoms and for general psychopathology than for negative symptoms. There was also a significant correlation between NAA concentration and social functioning within the schizophrenic group. There were no significant differences between the two groups for the three metabolites. CONCLUSIONS: The negative association between severity of symptoms and NAA in schizophrenic patients and an association of NAA with social functioning suggest that NAA may be an indicator of disease severity. The lack of significant mean difference in NAA between the two groups suggests that there is no marked neuronal loss in the dorsolateral prefrontal region in schizophrenia.
Asunto(s)
Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Metabolismo Energético/fisiología , Lóbulo Frontal/fisiopatología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Corteza Prefrontal/fisiopatología , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adulto , Mapeo Encefálico , Colina/metabolismo , Creatina/metabolismo , Dominancia Cerebral/fisiología , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Fosfocreatina/metabolismo , Corteza Prefrontal/patología , Escalas de Valoración Psiquiátrica , Valores de Referencia , Esquizofrenia/fisiopatologíaRESUMEN
The authors investigated the thalamus in schizophrenia by using magnetization transfer ratio (MTR), a novel structural magnetic resonance technique sensitive to subtle neuropathological abnormalities. The dorsomedial nucleus (DMN) and pulvinar were selected because of their connections to limbic, prefrontal, and temporal regions, putatively relevant in schizophrenia. Volume (intracranial; thalamic) and MTR (whole thalamus; DMN; pulvinar) were determined in 25 patients with chronic schizophrenia by DSM-IV criteria and 25 control subjects. There were no significant differences between patients and control subjects in thalamic volume (corrected for intracranial volume) or MTR in whole thalamus, DMN, or pulvinar. No volumetric or MTR abnormalities could be detected in the thalamus of patients with schizophrenia. The findings suggest that abnormalities, if present, are very subtle and beyond the power of resolution of these techniques.