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Brain function clues found in depressed patients (2/25/97)

Antidepressant drugs don't help some severely depressed patients.

Now, thanks to research using positron emission tomography (PET) images that can show chemical changes in the brain, researchers have begun to learn why.

New findings from the Research Imaging Center and the Department of Psychiatry at The University of Texas Health Science Center at San Antonio, published in the March 3 edition of the British journal *NeuroReport* (Vol. 8, Issue 4), point to an area of the brain with a signature metabolic pattern that seems to be necessary for recovery from depression.

"A significant number of depressed patients fail to improve with standard treatment and there have been no reliable tests to predict which patients these will be," says Helen S. Mayberg, MD, lead author on the paper. Dr. Mayberg is associate professor of medicine/neurology, psychiatry and radiology. "Although there have been earlier brain imaging studies of patients with depression, and abnormalities in various areas were described, no clear reason for reported differences in patients has ever been defined."

The San Antonio study found that individuals tested before treatment who had lower than normal glucose (a form of sugar) metabolism in a brain area called the rostral anterior cingulate gyrus were the ones most likely to not respond to antidepressant medication. The cingulate gyrus is one part of the limbic system, an area of the brain long thought to regulate emotions. Those with a higher than normal glucose metabolism in the same area were most likely to improve on medication.

"These findings allow us to propose a critical role for this specific region of the brain in the complex brain network used to regulate normal and abnormal mood states," Dr. Mayberg says. "They also point to the possibility of using PET results to help with diagnosis and management decisions for individual patients."

The study involved 18 depressed patients and 15 non-depressed volunteers. Following PET scans and MRI scans, antidepressant treatment was begun in all patients. Patients received one of several antidepressant drugs with differing mechanisms of action and clinical response was assessed after six weeks.

The PET scans made prior to treatment uniquely differentiated those patients who would eventually respond to treatment from those who would not. The researchers found that this method of prediction was statistically much more significant than any other clinical measure such as age, gender, length or severity of illness, number of previous episodes, past medication use, suicide risk or performance on neuropsychiatric tests.

"Our current thinking is that perhaps the rostral cingulate region serves as a critical bridge, linking pathways necessary for the normal integration of mood, motor, cognitive and vegetative (sleep, libido, motivation, appetite) behaviors, all of which are disturbed in patients with depression," Dr. Mayberg says. "The results of this study suggest that an adaptive functional response in this region of the brain is necessary for patients to respond to drug treatment, and we can measure this response with PET.

"If these findings are replicated," she says, "the evaluation of metabolism in the rostral cingulate region prior to treatment may provide some important predictive information. Greater than normal metabolism will allow us to more confidently advise our patients that they are likely to do well with treatment. The lower metabolic signature will help us to target those patients who are at risk for a rockier disease course and who require close clinical follow up and more aggressive treatment."

The study was funded by the National Alliance for Research on Schizophrenia and Depression (NARSAD), the largest publicly- supported, non-governmental funder of psychiatric research in the nation. Dr. Mayberg received a 1996 Gerald L. Klerman Award from NARSAD for her outstanding work in depression research.

Authors from the Health Science Center in addition to Dr. Mayberg include Dr. Stephen K. Brannan and Dr. Roderick K. Mahurin, psychiatry; Dr. Paul A. Jerabek, research imaging center and radiology; Dr. Jerold S. Brickman, research imaging center; Dr. Janet L. Tekell and Dr. J. Arturo Silva, psychiatry; Scott McGinnis, research imaging center; Dr. Thomas G. Glass, research imaging center and radiology; Dr. Charles C. Martin, research imaging center and radiology; and Dr. Peter T. Fox, psychiatry, neurology, radiology and director of the research imaging center.

Contact: Mike Lawrence (210) 567-2570