March 24, 2006

Heckers highlights latest advances, obstacles in schizophrenia research

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Stephan Heckers, M.D., chair of Psychiatry at VUMC, delivered the Brain Awareness Month keynote address. He spoke about advances in understanding schizophrenia.
Photo by Dana Johnson

Heckers highlights latest advances, obstacles in schizophrenia research

In ancient times, the “split mind” of schizophrenia might have been attributed to possession by demons and evil spirits. Nearly a century since it was identified as a distinct type of brain disease and given a name, the condition continues to puzzle clinicians and researchers.

The history and pathology of schizophrenia was the topic of the Brain Awareness Month keynote address, delivered by the new chair of Psychiatry at Vanderbilt University Medical Center, Stephan Heckers, M.D.

In his presentation, Heckers discussed advances in the field and the obstacles to defining identifiable anatomical changes in the brains of patients with schizophrenia.

In the early 1900s, the “classical period” of schizophrenia research, numerous postmortem studies aimed at finding the structural basis of schizophrenia came up short.

“The classical period ended in 1952 when the First World Congress of Neuropathology met in Rome,” Heckers said. “The scientists at the meeting concluded that that there was no identifying pathology of schizophrenia.”

For decades, schizophrenia research stalled. But the advent of new imaging technologies of computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI) in the 1970s and 1980s reinvigorated the search for the neuropathology of schizophrenia.

With the detailed imaging studies, researchers began to see a number of brain changes. The hippocampus, a small region of the brain ignored in the early postmortem studies, became a focus, and a particular interest of Heckers.

The hippocampus, which is only 3-4 cubic centimeters and makes up less than 1 percent of the entire brain, plays a crucial role in formation and retrieval of memories.

“If you lacked this structure, you would not remember me a minute after you met me,” Heckers said.

Researchers found significant decreases (5 to 10 percent) in hippocampus volume in schizophrenia patients.

The change was evident early in the illness and studies in relatives of schizophrenia patients have shown similar changes, even in the absence of symptoms. Those relatives are also at an increased risk of subsequently developing schizophrenia.

In addition to these gross anatomical changes, Heckers then detailed some of the brain changes at the microscopic level, including the decrease in inhibitory interneurons of the hippocampus.

Although only a very small overall decrease, this loss can upset the electrical balance and make the brain vulnerable to “electrical arrhythmias” that may underlie hallucinations.

Focusing in even closer, Heckers discussed a number of genetic changes linked to schizophrenia.

However, no single gene basis for schizophrenia has been found.

“We have made the first really promising inroads into the genetics of the illness,” Heckers said. “We've identified risk genes that increase the likelihood of the development of schizophrenia, but we have not yet identified genes that truly code for the illness.”

Heckers' keynote address was part of a month-long series of Brain Awareness events aimed at teaching the general public about how the brain works and the importance of brain research to understanding, treating, and ultimately curing brain-related diseases.

The presentation was co-sponsored by the Vanderbilt Center for Integrative and Cognitive Neuroscience, the Vanderbilt Brain Institute and the Middle Tennessee Chapter of the Society for Neuroscience.