Brain's Serotonin System Declines With Age Shows UPMC Research

November 04, 1997

PITTSBURGH, Oct. 29 -- The serotonin system, an aspect of the brain's neurochemical structure associated with behavior and mood, has been shown to substantially decline with age, according to research with living humans ages 18-76 at the University of Pittsburgh Medical Center funded by the National Institutes of Mental Health and presented at the annual meeting of the Society for Neuroscience in New Orleans.

The results reported by Carolyn Cidis Meltzer, M.D., assistant professor of radiology and psychiatry and acting medical director, Positron Emission Tomography (PET) Facility, and her colleagues have considerable implications for future studies investigating the delicate balance of brain serotonin and its possible role in the development of depression in the elderly and Alzheimer's disease. Understanding this vital chemical system may pave the road for developing more effective treatments aimed at controlling these and other debilitating medical conditions.

Recognition of the importance of serotonin has become widespread, particularly with the success of Prozac and other medications that achieve a positive result for patients with depression. Prozac works by leveling swings in serotonin levels. Regulating serotonin may help control eating disorders, alcoholism and other mood disorders, researchers say.

Dr. Meltzer and her colleagues examined the serotonin system by focusing on one of the most important of the 14 types of receptors (or binding sites) for serotonin. A radioactive form of a drug called altanserin was given to young and older healthy people before PET scanning was used to take pictures of the distribution and number of serotonin receptors in the brain.

Participation in the study involved an approximately four-hour visit to the research facility. Magnetic resonance imaging (MRI) was also performed to obtain detailed pictures of the anatomy of each person's brain. Knowledge of the brain's anatomy guides the interpretation of the PET images and is used to determine exactly which brain areas are deficient in serotonin.

The 55 percent decline in serotonin receptors was demonstrated in several areas of the brain and persisted even after normal aging changes on the brain's anatomy were taken into account. Prior postmortem studies have suggested aging changes in the serotonin neurotransmitter system. Prior PET serotonin studies with living humans were plagued by two factors: 1) contamination from dopamine and other neurochemical systems, and 2) failure to correct for the effect of normal age-related changes in the shape of brain structures that can falsely cause an apparent decline in measurements on PET images when comparing young and elderly individuals. A previous study done in Belgium that corrected for only the first of these problems used a narrower age range of subjects (24-48 years) and studied only nine people.

Dr. Meltzer's colleagues for the aging and serotonin study were Steven T. DeKosky, M.D., professor of psychiatry, neurology and neurobiology; Charles F. Reynolds, III, M.D., professor of psychiatry and neurology; Gwen Smith, Ph.D., assistant professor of psychiatry and radiology; Bruce Pollock, M.D., Ph.D., associate professor of psychiatry and pharmacology; Julie Price, Ph.D., assistant professor of radiology; and Chester A. Mathis, Ph.D., associate professor of radiology.

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