Scientific study links pair of genes with severe depression
Researchers have found two genes that can mutate to predispose people to suffer deep depression, one specific to women, the other a regulator of a key brain chemical messenger common to both sexes. A study involving the messenger serotonin, published Friday in the journal Science, shows for the first time that a gene might determine whether stressful events will make you depressed.
The second study, appearing in the journal Molecular Psychiatry, indicates that genetic differences at least partially account for why women are twice as likely as men to develop depression.
Depression affects nearly 10 percent of people worldwide. Typically, it’s considered a period of at least two weeks when a person falls into a permanently sad, depressed mood. The ability to function at work and home is diminished. Other changes in physical and mental states, such as sleep problems, accompany the illness. While scientists have made great progress in developing drugs to treat depression, doctors often have to try a number of treatments before finding one or more drugs that provide relief. Understanding genetic factors of the disease might lead to more specifically targeted therapies, the researchers say.
In the Science study, the international team of researchers concluded that people with one version of the serotonin gene, called 5-HTT, are more vulnerable to becoming depressed after a string of stressful events than are those with different combinations of the gene. Scientists say the short version is not as effective in controlling serotonin flow as the long version.
“We are not reporting a gene that causes a disease. Instead, we believe the gene helps influence whether people are resistant to the negative psychological effects of the unavoidable stresses of life,” said Terrie Moffit, a professor of psychology at the University of Wisconsin-Madison and King’s College in London.
Every human carries two copies of the 5-HTT gene – either the short or long variant, or one of each. Moffit said nearly two-thirds of the population carries at least one copy of the short version.
The researchers used data from a long-term study conducted by the University of Otago in New Zealand. The study tracked the health and development of more than 800 young adults in that country. The researchers determined each subject’s 5-HTT gene type, evaluated them for signs of depression in the past year and recorded their stressful life events – such as financial problems, physical illness, abuse and relationship breakups – over a five-year period.
Among those having four or more life stresses during that time, 33 percent who had at least one copy of the short variant, and 43 percent of those with two copies, developed depression. Only 17 percent of those with two copies of the long version suffered from depression.
In the Molecular Psychiatry study, Dr. George Zubenko and colleagues at the University of Pittsburgh School of Medicine found that a variant of a regulatory gene called CREB1 contributed to development of depression in women, but not men, while a second variant seemed to protect women.
“More than 80 percent of the women in our study who inherited a particular variant of CREB1 developed depressive disorders, while a second version of the gene appeared to have protective effects,” Zubenko said.
His team previously studied genetic factors for depression among more than 1,200 members of 81 families having unusually high rates of major depression compared to similar groups in their community. Their new research is an outgrowth of that work. CREB1 directs a protein called CREB, which in turn coordinates the work of a large number of other genes.
Zubenko said this widespread function of CREB suggests that the newly identified variants could influence development of disorders related to depression, such as alcoholism and other substance-abuse problems.
He said interactions of CREB with estrogen receptors might explain how inherited variants of CREB1 could affect susceptibility to major depression only in women.
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(Contact Lee Bowman at BowmanL(at)shns.com or online at http://www.shns.com)
AP-NY-07-17-03 1400EDT