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Frans_Jozef
Saturday, January 1st, 2005, 05:39 PM
Environment is key to serotonin levels


By Beth Azar


Are scientists close to developing a pill to rid society of violence, addiction, obesity and a host of other social ills?

The media seem to be making that prediction as they report the deluge of new studies on the neurotransmitter serotonin. An article in U.S. News and World Report even asked 'Does everything come down to serotonin?' Its answer? 'Yes.'

The studies are finding a correlation between low levels of serotonin and behaviors that include overeating, alcoholism, depression, aggression and suicide. So give people a 'booster shot' of the neurotransmitter, via medications like Prozac, and eliminate the problems, right?

The concept makes theoretical sense: Most of these disorders involve a breakdown in impulse control, and serotonin is known to put the brakes on other neurotransmitters that encourage impulsive behaviors.

But serotonin's role is not that simple, researchers say. If anything, work they've done so far highlights how complex serotonin is and the integral role environment plays in shaping who we are and how we behave.

'The most important message our research can make is that experience is as strong or stronger than anything that's inherited,' said psychologist Stephen Suomi, PhD, chief of the Laboratory of Comparative Ethology at the National Institute of Child, Health and Human Development.

Suomi and his colleagues have evidence that a monkey's childhood environment can have dramatic effects on its behavior and its serotonin system. Other studies indicate that trauma during a hamster's adolescence can damage the animal's ability to cope with stress by disrupting a complicated neurotransmitter system, which includes serotonin.

Work in humans hasn't yet found these developmental correlations, but does show some parallels to the work in animals.
Impulsive primates

Many studies have found that low serotonin levels in adults are linked to aggression, alcohol abuse and mental illness. But evidence to date doesn't indicate whether low serotonin causes the problems or the problems cause low serotonin. That's why Suomi, Dee Higley, PhD, and their colleagues at the National Institutes of Health (NIH) Primate Center in Poolesville, Md., study the link between behavior, serotonin and environment in rhesus monkeys.

They've found that 5 percent to 10 percent of monkeys in wild and laboratory populations are unusually impulsive and aggressive. These monkeys also have the lowest levels of serotonin compared with the rest of the population.

Like most researchers, Suomi and Higley estimate amounts of serotonin by measuring the concentration of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the fluid surrounding the spine and brain. Monkeys with low 5-HIAA demonstrate impulsive behaviors in late childhood: Their play bouts often build into fights and their peers shun them. In the lab, they're antisocial, inappropriately aggressive and will drink to intoxication if given access to alcohol. (Normally, monkeys will only drink moderately).

In the wild, these monkeys seek out danger, often making risky leaps between trees that other monkeys would never attempt, said Higley, an intramural researcher at the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

These traits can have dire consequences. Male rhesus monkeys typically leave their home troupe at puberty and find their way into another group. But troupes oust impulsive males well before adolescence. They tend to become loners, unable to win acceptance into another troupe, are unsuccessful at mating and often die within a year, said Suomi.

Some of these males may pass on their genes but, if 5-HIAA concentration is an inherited trait, it more likely comes through the mother, said Higley. Females with low serotonin are also impulsive, aggressive and disliked, but more often reproduce. They also make poor mothers, and recent research in the lab indicates that a poor rearing environment can affect behavior and 5-HIAA concentrations, said Higley.

'Just because a trait runs in families, doesn't mean it can't be influenced by the environment,' said Higley. 'Our research is a prime example that low serotonin is likely a mix of genetics and environment.'

In a recent study, Higley, Suomi and NIAAA scientific director Markku Linnoila, PhD, found that monkeys raised without their mothers--with only their peers for support--had low 5-HIAA, compared with mother-reared monkeys. They measured the differences as early as 14 days of age and into adulthood. Peer-reared monkeys were also socially inept and excessively aggressive--more so than mother-reared monkeys with low 5-HIAA.

These finding indicate that a poor rearing environment can aggravate behaviors already caused by low 5-HIAA, the researchers concluded in Alcohol, Clinical and Experimental Research (Vol. 20, No. 4, 643-649). They are now investigating whether an exceptionally good rearing environment--one spent with an attentive, highly caring mother--can eliminate problems associated with low 5-HIAA.

In contrast, the researchers found that immediate environment can also influence behavior above and beyond serotonin level. Peer-reared monkeys drank significantly more alcohol than mother-reared monkeys, with a correlation between low serotonin and heavy drinking. But that difference disappeared when the researchers separated the monkeys from their social group--a highly stressful situation for monkeys. Both groups drank heavily, they found.

'Serotonin and its behavioral correlates--impulsivity and aggression--are highly subject to experiential effects, especially early in life,' said Suomi who believes that these early life experiences can be modified with behavioral interventions.
Hamster trauma

Work with golden hamsters by Craig Ferris, PhD, indicates an even more complicated system of checks and balances, involving two neurotransmitters--serotonin and vasopressin--and their interaction with the environment. Ferris is a neuroscientist in the Behavioral Neuropsychiatric Sciences Program in the psychiatry department at the University of Massachusetts Medical Center in Worcester.

His work has found that traumatic experiences early in life affect hamsters' neurobiology, as well as their behavior. When hamsters reach adolescence they leave their home nest and stake out their own, solitary territory. To study the impact of trauma during adolescence on hamsters, Ferris and colleagues Richard Malloni, PhD, and Yvon Delville, PhD, once a day for a week--almost half a hamster's adolescence--placed adolescent hamsters in an older hamster's home cage once a day for a week--almost half a hamster's adolescence. Because hamsters are highly territorial, the older hamsters threatened and nipped the adolescents.

When the emotionally traumatized hamsters reached maturity, the researchers watched how they reacted when another hamster entered their territory. The victimized hamsters ran away from hamsters that were their own size, but showed heightened aggression toward smaller or weaker intruders, compared with a group of hamsters that weren't traumatized during adolescence.

When he examined the brains of the hamsters, Ferris found a change in the vasopressin and serotonin systems. The hamsters were producing less-than-normal amounts of vasopressin and an abundance of serotonin. These results are somewhat counter-intuitive because normally, vasopressin facilitates aggression and serotonin inhibits it. In these hamsters, however, the balance of the two neurotransmitters is upset, for reasons as yet unknown, and causes unusual behavior in a specific context, he believes. The hamsters behave no differently than nontraumatized hamsters until they're threatened.

Part of the difference between his hamsters and the low serotonin monkeys is the hamsters' lack of impulsivity, which indicates the complex nature of the neurotransmitter system, he added. Ferris suspects that any changes in the serotonin system lower an animal's threshold for handling stress.

Environmental triggers can then stimulate behaviors. This is similar to mental illness, where symptoms seem to worsen when patients are under stress from their environments, said Ferris.
Research with humans

A similar cascade seems to occur in suicidal people, according to J. John Mann, PhD, of Columbia University and the New York State Psychiatric Institute. People who commit suicide almost always have some form of mental illness, studies find. But mental illness alone doesn't provoke people to kill themselves, and the severity of a person's illness does not increase the likelihood of an attempt, studies find.

Instead, people who commit suicide tend to be impulsive, aggressive and less able to handle the pain of their mental illness. Mann suggests that this inability to cope allows people to act on suicidal thoughts that otherwise would go unheeded. Scarce serotonin supplies may be the factor that lowers this coping threshold.

Studies find that serotonin sys-tems in suicide victims and serious suicide attempters is impair-ed. Anything from genetic factors to alcohol dependence to poor family support may affect the serotonin system, Mann believes.

Because so many psychiatric disorders and problem behaviors have been linked to low serotonin, it's difficult to conclude anything causal from the research to date, said University of Southern California psychologist Adrian Raine, PhD. Both heredity and the environment can affect the serotonin system, as can many disorders associated with low serotonin.

It's certainly too early to be talking about a pill for our social ills, agree the researchers. Indeed, they are most intrigued by data pointing to the importance of the environment that animals and humans grow up in.

'What this work says is that we might not have a problem if we attend to our children early in development,' believes Ferris. But without understanding the biological risks, researchers would be missing a piece of the puzzle, said Raine. 'And if that's the case we'll never be able to solve the problem without examining all the leads these studies point to.'