SAN DIEGO - New studies have for the first time directly confirmed the long-held belief that low levels of the brain chemical serotonin produce aggressive behavior in humans, researchers said yesterday.
The studies, presented here at a meeting of the Society for Neuroscience, are expected to lead to new ways to treat potentially violent individuals. Already they have prompted successful clinical trials of a new drug, fluvoxamine, that reduced violent episodes among adults with autism and enabled them to lead more normal lives.
Researchers had found that low levels of serotonin in the body could be correlated with aggressive behavior and other disorders. But there have always been questions about whether the observations were coincidence or cause and effect.
In the new studies, researchers at the University of Texas and Yale University manipulated diet to lower artificially the concentration of serotonin in the brain. When this was done to healthy individuals, they became more aggressive until the effects wore off. When done to autistic individuals, they exhibited more-severe symptoms of their disorder, especially violent aspects such as self-hitting and self-biting.
The studies will provide insight into the root causes of violence, said neuroscientist Floyd Bloom of the Scripps Research Institute. They also demonstrate, he added, that "perhaps the way to a man's brain is through his stomach."
Serotonin was one of the first neurotransmitters - chemicals that carry messages between brain cells - to be discovered and is one of the most widely studied. It has been linked, said Bloom, to a broad variety of ailments, ranging from depression and obsessive-compulsive disorder to anxiety and eating, sleeping and sexual dysfunctions.
To prove that low levels of serotonin can cause aggression, Texas neuroscientist Frederick Moeller took advantage of a dietary-research technique originally developed at Yale. Serotonin is produced in the body from the amino acid tryptophan, one of the 20 or so amino acids that are the building blocks of proteins. Tryptophan is an "essential amino acid," meaning it is not produced in the human body and must be consumed, in such foods as milk, turkey, bananas and pineapples.
Yale researchers have shown that if a person is fed a low-tryptophan diet for 24 hours, then given a milkshake containing 16 other amino acids, but not tryptophan, his or her body undergoes a burst of protein production that depletes tryptophan - and thus serotonin - from the brain and blood.
Moeller submitted 10 healthy males to this regimen, giving them the tryptophan-depleted milkshake one week and a tryptophan-containing shake another week. Neither researchers nor volunteers knew which was which.
About five hours after the shake, when tryptophan levels were at their lowest, the volunteers played a game in which, paired with a partner, they could earn points that were worth money. They also had the opportunity to take points away from their opponent without any benefit to themselves - an aggressive act that Moeller termed simply "mean."
All volunteers were more aggressive when their serotonin levels had been depleted, but some were significantly more aggressive than others.
This suggests, he said, that "there may be some individuals who are more prone to this effect, such as people with a history of early-onset aggressive behavior. If true, these people may benefit from medications which increase serotonin."