Hearing could hold key to unlocking schizophrenia mystery

Measuring brain waves in response to hearing a variety of tones appears to be a useful way to begin understanding the underlying genetic abnormalities associated with schizophrenia, says a study headed by researchers at Harvard-affiliated McLean Hospital.

In the paper “Reductions in the N1 and P2 Auditory Event-Related Potentials in First-Hospitalized and Chronic Schizophrenia,” available online through Schizophrenia Bulletin, Dean F. Salisbury, director of the Cognitive Neuroscience Laboratory at McLean, reported that brain activity in response to certain tones was abnormally reduced among subjects hospitalized for the first time with schizophrenia, compared to healthy subjects whose brain wave responses were recorded after hearing the same tones.

The response patterns are expected to be used as a way to identify genetic patterns that could one day lead to the development of smart drugs tailored to patients’ individual genetic differences, said Salisbury, who is also an associate professor of psychiatry at Harvard Medical School (HMS). He co-authored the paper with K.C. Collins of McLean and Robert W. McCarley, professor of psychiatry at HMS and Head of the Harvard Department of Psychiatry and Laboratory of Neuroscience, of Boston Veterans Affairs Healthcare System.

“This is the first time this [brain wave] abnormality has been shown in first-time hospitalized patients and we’ve shown it using a couple of different sounds,” Salisbury said.

First-time hospitalized patients were used because of the possibility that brain wave responses might be altered in patients already on medication for the disease. Previous studies had shown chronically ill patients also had reduced brain wave activity in response to hearing tones, but it was thought that perhaps the long-term effects of medications may have caused the reductions. This study shows similar reductions in patients medicated for only a brief time or not at all.

“This is only a small piece of the puzzle, but it adds to our increasing knowledge and may turn out to be an aid in determining the underlying genetic structure of the disorder,” Salisbury said.

There is no one gene for schizophrenia, although a number of genes have been associated with the disorder, which is characterized by hearing voices, unusual thoughts, impaired thinking, and language problems.

The idea to measure brain activity in response to certain types of beeps came because schizophrenia is thought to involve the brain’s left temporal lobe, which is involved in sound and language processing, according to Salisbury.

“We use simple hearing tests as a probe of auditory function and temporal lobe symptoms,” he said.

More than 100 first-time patients were tested over a period of nearly 10 years.

The fact that brain response to these tones was abnormal in these patients might indicate that the brain is not firing properly in the auditory cortex or that there is structural damage to that part of the brain, or both, although the study did not seek to determine why responses were abnormal, he said. The point was to find out if they were abnormal. The fact that they were suggests the researchers are on to something and that continued research is needed.

“The brain wave response to tones is a reductionistic measure,” Salisbury explained. “It is a very simple brain event coming from a small part of the cortex, but represents an important function of the brain. It is much simpler than something as complex as a thought or memory, which likely involves many different brain functions across many different brain areas. Trying to find one gene related to a disordered thought is likely impossible. Finding one gene related to an early brain response occurring in a well-defined part of the brain is much more likely.”

Once specific gene subsets are identified, drugs can be tailored to patients with those subsets, he said.

“A drug therapy that might improve performance in one genetic pattern might actually impair performance in another,” he said. “Having a better understanding of what the person’s underlying pattern is can tailor the therapeutic intervention. This finding is interesting and shows it can be a tool for further genetic studies. The important implication is that we can use the brain waves to drive the genetic analysis.”