I work as a scientist doing clinical research. My focus is schizophrenia. Early on, while still in junior high school, I became fascinated with the scientific world and with the experimental method, i.e., asking questions within a hypothesis-testing framework to provide clear and certain answers. The experimental method is the same in clinical research as in the more basic sciences, only a bit more difficult to effect because human persons are involved. However, the answers seem more important because any break-through will ease human suffering. One of the human diseases causing immense human suffering has an unknown pathophysiology and etiology; it is schizophrenia. Schizophrenia is an illness that has its onset in early adult years and lasts a lifetime. The tragedy of the illness lies in the fact that the core thinking and experiential capacity of the person with the illness is critically affected. Those human characteristics which many of us prize most highly—the ability to use our minds, to think critically, to plan future work and events—are most affected in the illness. Schizophrenia causes persons to misconstrue the world around them, such that reality "plays tricks" on their minds. The experience of the world around a person with schizophrenia is twisted and incorrect, yet they experience it as real. I was drawn to study this mental illness because it is in critical need of scientific attention and because the advances in the basic neurosciences have developed to the point where they can conceivably be used to explain phenomena in psychotic illnesses.

Because schizophrenia is primarily a human illness, answers to the questions of pathophysiology must come first from studying persons with the illness. We recruit persons with schizophrenia who are willing to participate in clinical research studies. They receive testing for their cognitive, motor, and affective function along with a state-of-the-art diagnosis. Then they are studied using functional brain imaging techniques with task or other probes to stimulate brain activity patterns. These kinds of information reveal which regions of brain appear to function abnormally and under which conditions. This makes a direct study of those brain areas in postmortem human tissue studies rational. We have now determined that limbic brain structures are most consistently functionally altered in in vivo imaging studies in our laboratory; therefore, we have now targeted these structures for postmortem study in schizophrenia. We routinely sample the hippocampus, entorhinal cortex, anterior thalamus, and anterior cingulate cortex from the donated brain tissue from persons with schizophrenia and from matched normal control tissue, and we evaluate anatomic, histologic, neurochemical, molecular, and genetic targets in this tissue. We hope to identify the pivotal molecular and cellular processes that are abnormal in these areas in schizophrenia, and strategies to correct them. This information, where it is available, would facilitate new treatment development.

Once the primary pathophysiology of schizophrenia is known, then rational therapeutic development can proceed to provide therapeutic agents that will restore health to persons with schizophrenia, not just manage symptoms, as do the medicines we have today. While clinicians are grateful to have the current medicines today which improve symptoms in schizophrenia, these current medications are not a cure for the illness. Rational therapies are still only theoretical. Despite this, the current medications, both the first-generation drugs like haloperidol and the second-generation compounds like clozapine, risperidone, and olanzapine are part of the everyday armamentaria of psychiatrists in treating with persons with psychosis.

My work in this area has been directed toward the development of new findings in schizophrenia to open up rational therapeutic directions for persons with the illness.

Dr. Carol A. Tamminga
University of Maryland School of Medicine & the Maryland Psychiatric Research Center
Baltimore, MD, USA