About the Psychiatry Neuroimaging Laboratory

History of Schizophrenia Research

One of the problems with investigating disorders such as schizophrenia is that the tools available in the past to evaluate subtle, small changes in the brain have been rather crude. Thus most of the work done in the past century to investigate brain structural abnormalities in schizophrenia was based on methods that were crude, prone to error, and it therefore did not further our knowledge and understanding of brain abnormalities in schizophrenia. This is not to say, however, that structural brain abnormalities were not thought to underlie the symptoms observed in schizophrenia. In fact, early documentation of abnormal brain structures from post-mortem studies of schizophrenia led to the formulation of quite specific hypotheses concerning the relations between brain and behavior.

These early studies, however, were hampered by inconsistent findings, crude measurement techniques, and carefully methodologically controlled studies often led to negative findings. This turn of events led many investigators to conclude that there were no structural brain abnormalities observed in schizophrenia that could not also be seen in normal controls. Progress in this area of research thus came to a near standstill and it was not until 1976, with the advent of computed tomography (CT), that the first CT study of schizophrenia reported abnormally large lateral ventricles in schizophrenic patients. This one study led to numerous CT studies, which confirmed abnormalities in the brains of schizophrenic patients, and this one study led to a renewed interest in investigating such abnormalities in schizophrenia.

The early CT studies evaluated only ventricular size and did not evaluate local regions of interest nor could gray and white matter be differentiated. With the advent of MR imaging, gray and white matter could be evaluated and thus a new tool was added. In 1984, the first MR study of schizophrenia was reported in the literature. Many studies followed, but most were based on magnets with a field strength less than 1.0, and the slice thickness was often 1 cm or more. Moreover, there were no methods for evaluating gray and white matter throughout the brain.

The first study to use contiguous slices of the entire brain (1.5 mm coronal and 3 mm axial), was done by our group and the findings were reported in The New England Journal of Medicine, August, 1992. Here, we reported small but important gray matter volume reduction in schizophrenic patients, compared to controls, in the amygdala-hippocampal complex, in parahippocampal gyrus, and in superior temporal gyrus, on the left. The latter changes were also correlated with disordered thinking and were thus suggestive of a disturbance in an important neural circuit involved in verbal processing and consolidation of information that involve both the amygdala-hippocampal complex and the superior temporal gyrus. These findings in schizophrenia would not have been possible without the availability of post-processing segmentation algorithms developed in the Surgical Planning Laboratory, with researchers working with Dr. Shenton being key players in driving the technology development.

The new laboratory, the Psychiatry Neuroimaging Laboratory, continues to work with the SPL in our mission to understand brain abnormalities in psychiatric disorders. This joint venture between the Departments of Psychiatry and Radiology has been a fruitful marriage between ideas, concepts, and questions concerning brain involvement in schizophrenia and related disorders, and the tools to address these issues. Progress in this area of research is now quite remarkable, and will likely lead to unprecedented advances in our understanding of structure-function relations not just in schizophrenia, but also in a wide number of other disorders affecting the brain.