11/11/2002 • Genes play a part, but violence may be viral

11/11/2002 • Genes play a part, but violence may be viral

By TOM SIEGFRIED
The Dallas Morning News
ORLANDO, Fla.

Harvard Medical School

This interesting article states: “Those genes are found in nerve cells (or neurons) that produce the brain chemicals dopamine and serotonin. When active, the genes tell the neurons to pump more of the chemicals into the fly’s nervous system. When the genes are turned off, dopamine and serotonin production falls off”.

“Some flies are genetically engineered with a “gene switch” that depends on temperature. Turn up the heat, and you turn off the genes. In this case, Harvard researcher Selby Chen and collaborators engineered flies who fight away when the temperature is a pleasant 77 degrees Fahrenheit. But when the scientists heat up the lab to a toasty 86, the flies equipped with a genetic switch in the dopamine and serotonin neurons throw in the towel. (Ordinary flies are happy to keep on fighting in the heat.) The apparent implication is that dopamine and serotonin genes play an important role in aggressive violence”.

Genes play a part, but violence may be viral

http://www.dallasnews.com/health/columnists/tsiegfried/stories/111102dnlivtomcol.13af7.html

By TOM SIEGFRIED
The Dallas Morning News
ORLANDO, Fla.

Harvard Medical School

This interesting article states: “Those genes are found in nerve cells (or neurons) that produce the brain chemicals dopamine and serotonin. When active, the genes tell the neurons to pump more of the chemicals into the fly’s nervous system. When the genes are turned off, dopamine and serotonin production falls off”.

“Some flies are genetically engineered with a “gene switch” that depends on temperature. Turn up the heat, and you turn off the genes. In this case, Harvard researcher Selby Chen and collaborators engineered flies who fight away when the temperature is a pleasant 77 degrees Fahrenheit. But when the scientists heat up the lab to a toasty 86, the flies equipped with a genetic switch in the dopamine and serotonin neurons throw in the towel. (Ordinary flies are happy to keep on fighting in the heat.) The apparent implication is that dopamine and serotonin genes play an important role in aggressive violence”.

It’s not exactly something you’d try to market for Pay-Per-View, but fruit flies sometimes stage some pretty fierce fights. Put two males in a laboratory ring and, under the right conditions, they’ll battle it out for the flyweight championship.

The scientists who serve as the fans at such fights aren’t interested in seeing flies bash their brains out, but rather are trying to understand something about brains in general.

It’s the brain, after all, that controls behavior, whether fighting or fleeing, speaking or thinking. Figuring out what goes on in a brain that tells it to fight might help reduce the risk of unnecessary violence in the world.

In the case of the flies, new research shows, violent aggression involves brain chemicals produced by specific genes. Turning off those genes induces the flies to stop throwing punches and return to their corners, Harvard Medical School scientists reported in Orlando, Fla., last week at the annual meeting of the Society for Neuroscience.

Those genes are found in nerve cells (or neurons) that produce the brain chemicals dopamine and serotonin. When active, the genes tell the neurons to pump more of the chemicals into the fly’s nervous system. When the genes are turned off, dopamine and serotonin production falls off.

Usually there’s not much you can do to manipulate genes quickly enough to stop a fight in mid-round. But fruit fly researchers have developed a neat trick for immediate gene control with a system that’s as simple as adjusting a thermostat. Some flies are genetically engineered with a “gene switch” that depends on temperature. Turn up the heat, and you turn off the genes.

In this case, Harvard researcher Selby Chen and collaborators engineered flies who fight away when the temperature is a pleasant 77 degrees Fahrenheit. But when the scientists heat up the lab to a toasty 86, the flies equipped with a genetic switch in the dopamine and serotonin neurons throw in the towel. (Ordinary flies are happy to keep on fighting in the heat.)

The apparent implication is that dopamine and serotonin genes play an important role in aggressive violence. But genes cannot be the whole story of violence in the animal kingdom.

Consider baboons, for instance. In the wild they are normally peaceful and live in harmony with their fellow primates. But after associating with humans for a while, baboons turn nasty. They attack each other rather viciously, in fact, sinking their fangs into the most sensitive of body regions. Females try to bite the tails off of other females.

“They just rip into each other,” says Timothy Smock of the University of Colorado at Boulder. “You wonder if they had guns, would they blow each other away. I’m quite convinced that they would.”

Dr. Smock and collaborator David Langoi, a veterinarian at the Institute for Primate Research in Nairobi, Kenya, have studied the brains of both peaceful and violent baboons. In the violent ones, a brain region called the superior temporal gyrus seems enlarged on the left side. In peaceful baboons that region seemed larger on the right side of the brain. For some reason, the violent baboons’ brains become modified in a way that promotes aggression.

Dr. Smock, who presented the findings at last week’s neuroscience meeting, does not know what causes the brain differences. But he has a suggestion that might be worth exploring. Maybe, he says, the aggression is the result of a virus. Perhaps there’s a virus for violence that somehow the baboons acquire from people.

“It’s total speculation,” Dr. Smock said in an interview. “But I’m hoping it’s a virus, because if we can find a virus that causes excessive violence, think about the implications for the type of insanity we’ve seen in the last 50 years. … The implications could be immense. ”

For one thing, a viral cause of violence would open a whole new avenue of understanding aggressive behavior. Much current research tries to draw conclusions about violence from studies of rats or mice. But such aggression, Dr. Smock points out, is typically not as senseless as the common human variety, but rather is directed toward specific goals involving territory or mates.

“We could possibly have a model for violence in people that’s different from simple aggression seen in rodents,” he said.

So far, though, there is no real evidence for the virus idea (although baboons do appear to acquire other diseases from humans, such as tuberculosis). And the preliminary findings are based on studies of only 10 baboon brains (five violent, five peaceful).

“We need to do a lot more work,” Dr. Smock acknowledged. For one thing, more intricate examination of the baboon brains is needed to determine whether some underlying defect is causing the enlarged regions seen on the surface.

Nevertheless, the idea of a violence virus is intriguing. Violent aggression may just turn out not to be only a societal sickness, but a medical one as well.

4/26/2001 – Part 2 – Luvox study on anxiety

http://www.washingtonpost.com/ac2/wp-dyn/A2512-2001Apr25?language=printer

Drug Found to Curb Kids’ Debilitating Social Anxiety

By Shankar Vedantam
Washington Post Staff Writer
Thursday, April 26, 2001; Page A01

Children who are so shy or so attached to their parents that they are afraid
to go to school or sleep alone do much better when given a psychiatric drug,
according to a major study with profound — and controversial —
ramifications for millions of children.

The study of 128 children ages 6 to 17 found that the drug Luvox, widely
prescribed for adults with depression, alleviated the debilitating symptoms
of social phobia, separation anxiety and generalized anxiety — psychiatric
illnesses that afflict as many as 1 in 10 U.S. children.

The effects of the medicine were dramatic, but experts were divided about its
appropriateness: The medicine can help children with severe emotional
problems, but it might also be abused as a chemical quick fix for normal
anxiousness, with lasting effects on growing brains.

“Although the results seem impressive, they nevertheless raise some very
important questions about the use of psychotropic medications in children,”
said Joseph Coyle, chairman of psychiatry at Harvard Medical School, in an
article accompanying the findings in today’s New England Journal of Medicine.

“Any drug that is effective is not going to be innocuous,” he said in an
interview. Children and adolescents diagnosed with these disorders should
first try a form of therapy known as cognitive behavioral therapy, and turn
to medication only if that fails, he said.

An estimated 575,000 children nationwide were diagnosed with anxiety
disorders in the 12 months ending in March, including 136,000 under age 10.
Doctors recommended 390,000 children be put on medicines such as Zoloft,
Paxil and Prozac. Of these, 89,000 were under age 10, according to IMS
Health, a private company that tracks the pharmaceutical industry.

Such vast numbers leave critics aghast. Too many children are being put on
powerful brain-altering drugs for behaviors that may be merely troublesome,
critics say. But other experts point out that many children suffer from
distress that, left untreated, can cause impairment well into adulthood.

“Researchers found that anxiety was among the most common problems that kids
have,” said Daniel Pine of the National Institute of Mental Health. He led
the study. “When researchers follow children with anxiety over time,
sometimes anxiety developed into more chronic problems. It could be the
harbinger of problems with depression, panic attacks and all different kinds
of problems.”

The study, the first large, well-designed survey to examine the effectiveness
of a psychiatric drug for a wide range of anxiety disorders in children, was
partly funded by the National Institute of Mental Health and by Solvay
Pharmaceuticals, which sells Luvox. The drug, which like Prozac increases
levels of the brain chemical serotonin, has been approved for the treatment
of obsessive compulsive disorder in children. Luvox sales were more than $2
billion in the United States last year, according to IMS Health.

Scientists at Johns Hopkins University, Columbia University, New York
University, Duke University and the University of California at Los Angeles
studied the drug over eight weeks in children with anxiety disorders.

An example of a child with severe social phobia would be one who refused to
go to school for two weeks, said Mark Riddle of the Johns Hopkins University
School of Medicine, one of the study’s authors. A milder example, he said,
would be a child who went to school and participated in clubs and group
events, but with intense discomfort.

Extreme separation anxiety disorder, he said, would be displayed in a child
who avoided birthday parties and sleepovers. A medium-grade example would be
children who refused to sleep in their own rooms and wanted to get into bed
with their parents.

Generalized anxiety disorder, Riddle said, were “the worrywarts.”

“A lot of it would be about performance — getting very preoccupied with a
test at school, a lot of fussing about day-to-day things,” he said.

“We don’t want a Prozac nation,” he said about the medication of children.
“We want to make sure we are not doing anything to harm youngsters. On the
other hand, it can be a huge disservice to children to minimize the true
significance of psychiatric impairments that do require treatments. It’s the
latter that can get lost in the very easy and popular position to take, which
is ‘Don’t drug our kids.’ ”

Richard Harding, president-elect of the American Psychiatric Association,
said clinicians should carefully evaluate anxious children to find out
whether their fears are caused by an underlying personality problem — which
would merit psychotherapy or medication — or by a social problem, such as a
bully in school or child abuse at home, in which case medication would be
inappropriate.

“A good clinician will not commit a child to a life sentence on medicine,”
said Riddle. “A good clinician will look to stop medication after the
youngster has had a chance to regroup. You want to work with a clinician who
says we are going to get John off this medication.”

It is unclear what impact this study will have in clinical practice, where
doctors are prescribing children such medicines “off-label” — meaning they
have not been approved for such uses by the Food and Drug Administration.

“Given our current medical-economic system in practice, I suspect both
doctors and parents will be strongly attracted to the quick-fix nature of
this intervention,” said Lawrence Diller, a behavioral pediatrician in Walnut
Creek, Calif., and the author of “Running on Ritalin.”

“We have highly effective psychosocial interventions for these problems,” he
said. But “they are more expensive and take longer.”

He said that helping families come up with parenting strategies could ease
children’s anxieties. “Children are highly responsive to their environments,
and the home is the practice arena to deal with life,” he said. “This is not
parent-blaming — children are difficult to raise. But when the parent makes
changes, you see very rapid changes in the child.”

“It doesn’t negate the value of the medications,” he added. But “with
uncertainty on both sides, effective psychosocial treatments — first do no
harm — take preference.”

More extreme critics, such as Bethesda psychiatrist Peter Breggin, said the
study was produced by scientists who are part of an “old boys’ network of
drug pushers.” He said the psychiatric drugs cause harm — some data have
shown that the drugs cause lasting alterations in the brains of young animals.

Researchers involved in the new study said the drug was well tolerated and
safe.

© 2001 The Washington Post Company