MR Volumetry and Schizophrenia: What have we learnt in the past 20 years?

Early brain imaging studies using pneumoencephalography have pointed out as early as in the 1920s and 1950s that there is ventricular enlargement and cortical atrophy in schizophrenia. The introduction of computed tomography in schizophrenia research in 1976 was helpful to support this line of evidence. Since then magnetic resonance imaging has helped considerably to establish schizophrenia as being a brain disorder. Structural brain imaging studies have helped to identify that there is a subtle loss of the whole brain volume in schizophrenia, an enlargement of the ventricular system, especially the lateral ventricles and the third ventricles, and regional loss of brain tissue in frontal but especially temporal lobe regions. The temporal lobe changes comprise volume reduction of the hippocampus, amygdala, entorhinal cortex, and superior temporal gyrus. In addition to these cortical findings, a volume reduction of the thalamus and the cerebellum can be replicated in recent studies. Most of these findings are present in an attenuated form in never-treated first relatives of schizophrenic patients. Between this genetic influence there seem to be environmental factors like obstetric complications adding to the extent of structural changes. However, it is clear that some of the changes predate the onset of the illness and are due to subtle remnants of a neurodevelopmental problem. In addition to these changes in the prodromes of schizophrenia, additional volume loss seems to occur. Finally there is some change over time in the course of the illness. Therefore, the structural changes seen in chronic schizophrenia are a mixture of premorbid changes, changes occurring in prodromal schizophrenia, and changes occurring during the course of the illness. Recent studies make clear that treatment in itself, and especially neuroleptic treatment, seems to add to the structural abnormalities. Atypical neuroleptics, for instance, seem to increase the volume of the basal ganglia and the thalamus, while typical neuroleptics seem to reduce the volume of the same structures. In summary, there seems to be a clear-cut pattern of structural abnormalities in schizophrenia. To some extent they are related to positive symptoms (hippocampus) and negative symptoms (cortical abnormalities) and are interesting indicators of disease processes underlying these changes. Functional and genetic studies are needed to elucidate the meaning of these changes on the non-structural level and pointing to their molecular bases.