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Emotional Disorders Linked to Brain Chemicals

December 4, 2004

Some, like serotonin, seem to contribute to anxiety, researchers say

HealthDayNews — Research continues to reveal the effect chemicals can have on the brain and how well it works.

What is emerging from intensive studies is the influence of certain chemicals already found in the brain. Scientists are looking for ways to make those substances more adaptable to individual needs.

Many of these neurochemicals are contained in brain cells known as neurons. Although there are millions of neurons in the brain, there is a space — or synapse — between each one.

Brain neurons communicate with each other by secreting chemicals that cross the space between the cells and bind to receptors on nearby cells. New studies in rodents suggest that many of the ways mentally ill people behave may actually result from malfunctions in these chemical connections.

One of these neurochemicals, serotonin, has received a lot of attention because it appears to affect emotional behaviors.

Rene Hen, an associate professor at Columbia University Medical Center’s Department of Neurobiology and Behavior in New York City, and his colleagues are looking at the role of serotonin in anxiety and mood disorders. In an ongoing study funded by the U.S. government’s National Institute of Mental Health (NIMH), the Columbia researchers created mice that didn’t have a protein needed to receive signals from serotonin. When these mice were adults, they exhibited symptoms of anxiety, just like humans do.

“The mice bred not to express the gene that codes for the serotonin receptor moved around less than normal animals in open spaces, balked at entering elevated mazes, and were slower to begin eating in such novel environments,” Hen said.

Still, the researchers needed to zero in what was causing the breakdown in serotonin reception. They eventually found out the exact location in the brain where the serotonin lapse had occurred — the forebrain.

Next, the researchers treated grown mice — those lacking the protein, those whose serotonin reception had been rescued, and normal mice — with a drug that shuts down serotonin receptors. Despite the shut down, the adult rescue mice continued to show normal anxiety-like behavior.

“From this we concluded that the receptor functions earlier in development to establish normal adult anxiety-like behavior,” Hen explained. And then the researchers — through cross-breeding — tried to find out how early in life normal anxiety-like behavior must be established.

Hen’s team determined that the critical period for establishing normal behavior in mice is between five and 21 days after birth.

“Serotonin stimulation of the forebrain receptor during this period likely triggers long-lasting changes in brain chemistry or structure that are essential for normal emotional behavior throughout life,” he said.

But as important as serotonin is, there are other brain chemicals that may be just as important in establishing the correct emotional balance.

In the Aug. 19, 2004, issue of Neuron, scientists at the University of California, Irvine and the Scripps Research Institute in La Jolla, Calif., reported the discovery of a new brain protein they believe may affect physical activity, wakefulness and the stress associated with several anxiety disorders.

This protein — which they named neuropeptide S (NPS) — is produced by previously unidentified neurons in the brain stem region known to regulate arousal and anxiety. Further tests demonstrated that rats injected with NPS showed increased alertness and reduced sleep patterns.

“We also found NPS receptor proteins in stress-related brain regions,” said Rainer Reinscheid, an assistant adjunct pharmacology professor at UCI and lead author of the study. “In behavior tests that measured stress-related anxiety, mice injected with NPS showed fewer anxiety responses and more activity than untreated mice.”

“Some 100,000 Americans are currently treated for excessive daytime sleepiness, but the number undiagnosed is far larger,” said study co-author Olivier Civelli, a professor of neuropharmacology at UCI. “The symptoms of sleepiness, often recognized as fatigue, are associated with numerous other illnesses, such as multiple sclerosis, Parkinson’s disease and also depression. If it can be shown that the NPS system is a major modulator of fatigue, then its therapeutic potentials will be immense.”

More information

Columbia University Medical Center’s Department of Neurobiology and Behavior

Find out more about research into the chemistry of mental illnesses from the National Institute of Mental Health.




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