Shortage of Chemical Causes Aggression, Studies Confirm

New studies have for the first time directly confirmed the long-held belief that lower-than-normal levels of the brain chemical serotonin produce aggressive behavior in humans, researchers said Sunday.

The studies, presented 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, called fluvoxamine, that reduced violent episodes among adults with autism and enabled them to lead more normal lives.

Researchers have previously found in epidemiological studies that low levels of serotonin could be correlated with aggressive behavior and a variety of other disorders. But there have always been questions about whether the observations were cause and effect or coincidence.

In the new studies, researchers at the University of Texas and Yale University manipulated diet to artificially lower the concentration of serotonin in the brain. When this was done to healthy individuals, they became more aggressive until the effects wore off. When it was done to people with autism, they exhibited more severe symptoms of their disorder, especially the more violent aspects such as hitting or biting themselves.

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 studied, according to Bloom, in connection with a broad variety of ailments, ranging from depression and obsessive-compulsive disorder to anxiety, eating, sleeping and sexual dysfunctions.

Researchers have long believed that low levels of serotonin are associated with violent, aggressive behavior. Dr. Markku Linnoila of the National Institutes of Health examined cerebrospinal fluid and blood from 1,000 prisoners in his native Finland and found that those who were most violent had the lowest serotonin levels.

Other studies have found similar results, but proof that the low levels caused the violence has been lacking until now.

In an attempt to provide that proof, Texas neuroscientist Frederick Moeller took advantage of a dietary research technique 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 that it is not produced in the human body and must be consumed from 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 men 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.”

Dr. Christopher McDougle of Yale performed the same experiment to deplete serotonin in 17 autistic adults and found that 11 had a significant increase in autistic behavior, including whirling, pacing, banging and hitting themselves, rocking and toe-walking. The patients were also less calm and happy, and more anxious.

In a subsequent experiment, McDougle treated 15 autistic adults with a drug that increases serotonin levels--fluvoxamine, which was approved earlier this year for treatment of obsessive-compulsive disorder--and compared them to a similar group who received a placebo. Eight of the 15 showed improvement of symptoms--but none in the placebo group. Some were actually able to go out and get a job for the first time in their lives.

He is now testing the drug in children.

Although autism is a relatively rare disease, affecting perhaps four of every 10,000 people, individuals who have it suffer all their lives. “There’s 60 to 70 years of impairment,” McDougle said.

The new results, he added, suggest that, “If we catch it early, we could modify the course of the disease and significantly reduce that impairment.”