March 2001

From Yale University

Study of schizophrenia patients who hear 'voices' to continue at Yale with over $600,000 in grants from NIMH, Dana and Donaghue Foundations

Research at Yale looking at the causes and treatment of auditory hallucinations or "voices" will continue with over $600,000 in combined funding from the NIH/National Institute of Mental Health (NIMH), the Donaghue Foundation and the Charles A. Dana Foundation.

"About 70 percent of patients with schizophrenia hear voices, with a population incidence of one percent overall," said Ralph Hoffman, principal investigator on the study and recipient of the grants. "This form of hallucination is very common and these symptoms are especially resistant to medications. About 25 percent of patients with auditory hallucinations respond poorly to drugs."

Hoffman adds, "Voices are particularly disabling, often producing great fear in patients, disruption of behavior, and, at times, lack of control, leading to behaviors such as suicide and assault. New methods that reduce voices therefore would be a significant advance."

Past studies done at Yale and elsewhere suggest that hallucinated voices may arise from brain circuits responsible for speech processing. Hoffman said that when given at a low rate of once per second, focal magnetic stimulation-brief, powerful magnetic pulses emitted by an electromagnet placed on the scalp-reduces activation in the underlying part of the brain.

"We therefore deliver magnetic stimulation at a low rate in these patients to an area of the scalp that is above and behind the left ear, which corresponds to a speech processing area," said Hoffman. "The relatively painless stimulation is about the same strength of an MRI and is administered while patients are awake."

In a study published last year in the Lancet, Hoffman and his team found that about half of the patients receiving this type of magnetic brain stimulation demonstrated clinically significant reductions in "voices." Duration of improvement was temporary, ranging from one to two days to two months.

One of Hoffman's current treatment studies, funded by the Donaghue Foundation and the NIMH, examines effects of giving more magnetic stimulation sessions-a total of nine in all, which is about three times the amount given in their previous study. "Preliminary results suggest that 60 to 70 percent of patients in this study have a significant response to magnetic stimulation, defined as a reduction in hallucinations of 50 percent or more," said Hoffman.

The current study is focused on patients whose hallucinations have been resistant to currently available drug therapies, and includes extensive psychological testing to determine effects of magnetic stimulation on concentration, language processing and memory. The study also includes a follow-up component to determine duration of symptom improvements after the trial is completed. Hoffman said, "Duration of improvement appears to be more extended, ranging between a couple of weeks to many months in patients studied thus far."

Fifty patients will be recruited nationwide and will be hospitalized at the Clinical Neuroscience Research Unit of the Connecticut Mental Health Center while in the trial.

Another study, funded by the Dana Foundation, will focus on patients with especially severe hallucinations that occur constantly during wakefulness.

These patients will undergo a PET scan to identify components of the brain ordinarily involved with processing speech that remain inappropriately activated due to persistence of continued hallucinated voices.

"Preliminary data suggest that among patients with especially severe hallucinations, brain activation producing hallucinations is more widespread and involves both left- and right-sided regions," said Hoffman. "We will use a computer system to direct the placement of magnetic stimulation, so that specific brain areas demarcated by the brain scan selectively receive magnetic stimulation. Therefore, location of the magnetic stimulation will be tailored to the individual patient, which may help us to obtain better therapeutic results."

These studies will be funded by an NIH/National Institute of Mental Health grant totaling $360,000 over three years; a Donaghue Foundation grant totaling $150,000 over two years; and a Dana Foundation grant totaling $100,000 for two years. Hoffman's colleagues on the two studies at Yale include Nashaat Boutros, M.D., James Duncan, Robert Innis, M.D., John Krystal, M.D., and Keith Hawkins. J. Douglas Bremner, M.D., of Emory University is also a collaborator on the study.












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