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Home: Articles: Dallas Morning News: Genetics Holds Clues

Genetics Holds Clues to Mental Disorders

Researchers Don't Have all the Pieces Yet

By Tom Siegfried and Sue Goetinck

Determining the cause of mental illness is like figuring out what makes good art.

Could anyone, given the right brushes and paints, produce a breath-taking canvas? Could the most accomplished painter, without the right materials, still create a masterpiece?

In each case, the answer is no. Great art requires both innate talent and the right tools.

In a similar way, miswired minds result from the wrong mix of nature and nurture.

As with many diseases, mental illness can run in families, suggesting that genetics plays a role. But genes don't tell the whole story. Sometimes one identical twin develops schizophrenia and the other doesn't, for example. Influences other than genes probably are the reason.

But such influences from the outside world - whether family relations, physical illnesses or traumatic experiences - are hard to measure. They aren't always available for scientific data-gathering. The hereditary aspect of mental illness is tough to pin down as well.

Although scientists know a lot about the brain, they are a long way from understanding the subtle differences that distinguish a healthy brain from one that doesn't work right.

"The human brain is far and away the most complicated thing we know in the universe," said Ken Kendler, a psychiatrist at the Medical College of Virginia in Richmond. "The liver and the kidney and the heart are all miraculous and extraordinarily complicated. But they are child's play compared to the brain."

Nonetheless, in recent years scientists have made substantial progress in identifying the genetic and environmental forces impelling people toward mental disorders.

For example:

  • Researchers recently reported new evidence for possible genetic links to manic depression on human chromosomes 4, 6, 13, 15 and 18.
  • In the past year, new studies have suggested that a gene involved in schizophrenia resides on human chromosome 6.
  • An unusual form of inheritance could be linked to mental disorders, providing a new clue to why the genetics of mental disorders are so complicated.

The latest research has solidified the growing conviction that for most mental illnesses, genetic susceptibility and outside influences conspire to cause the disease.

"I think it's very clear...that if you have a loaded family history for either depression or anxiety disorders, that means you have a genetic vulnerability," said Charles Nemeroff of Emory University in Atlanta." And coupled with that, if you have untoward life events, the likelihood that you will go on as an adult to develop a major psychiatric disorder is extremely high.

Nemeroff and colleagues recently published a study in the Proceedings of the National Academy of Sciences showing that stresses early in life can cause long-lasting biological changes in levels of a hormone known to be related to depression. The researchers stressed baby monkeys by forcing mothers to spend time away from their babies at erratic intervals to look for food. The mothers were upset and the babies were neglected, Nemeroff said.

A few years later, when the baby monkeys had grown, they had higher-than-normal levels of hormone known as corticotropin-releasing factor, or CRF. High levels of that hormone are known to be linked to depression. Studies with baby rats have produced similar results.

People who are neglected as children or are exposed to traumatic events such as violence could be getting set up for problems later in life, Nemeroff said.

In the rat studies, researchers were able to reverse many of the effects of early life stress by giving the rats the antidepressant Paxil.

"This raises a number of issues about when you should intercede...Should you treat patients either pharmacologically or psychotherapeutically? Should you treat children who have been exposed to trauma? This raises a number of issues about preventative psychiatry," he said.

While studies such as Nemerof's suggest that stress can contribute to depression, other research suggests that stress isn't the only factor.

A 1993 study by Kendler looked at possible causes of depression in women. Because the women studied were either identical or fraternal twins, the researchers were able to estimate the effect of genetics on depression. Besides genetics, the researchers checked for outside influences such as parental warmth, separation from parents, lifetime traumas, social support and recent difficulties or stressful events.

The study, published in the "American Journal of Psychiatry," concluded that stressful life events and genetic factors could both contribute to depression. In fact, Kendler said, researchers think that on average, about half the risk for depression vulnerability is due to genetic factors.

To understand what that figure means, Kendler said, consider the trait of height. Genes determine about 90 percent of how tall someone is, he said. The remaining 10 percent is determined by outside influences, such as nutrition. With susceptibility to depression, Kendler said, the genes-environment split is about 50-50.

©1996, Dallas Morning News

Modified December 25, 2002

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