Epic Genetics: Genes' Chemical Clothes May Underlie the Biology Behind Mental Illness

By Saey, Tina Hesman | Science News, May 24, 2008 | Go to article overview

Epic Genetics: Genes' Chemical Clothes May Underlie the Biology Behind Mental Illness


Saey, Tina Hesman, Science News


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In research circles the debate is settled. Psychiatric illnesses are disorders rooted in biology.

As convincing as the evidence is, mysteries still fog our understanding of mental illnesses. Yes, the disorders stem from problems in the brain, but "on the other hand, for time and ages people have been looking at brains under the microscope, and they don't see much," says Schahram Akbarian, a psychiatrist and neuroscientist at the University of Massachusetts Medical School in Worcester. No lesions, malformations, scars or other outward signs distinguish a mentally ill brain from a healthy one.

In recent years, researchers have searched the genome for mutations linked to mental illness. The scans have been fruitful, perhaps too fruitful. Hundreds of genes have been implicated in predisposing a person to such disorders as addiction, schizophrenia, bipolar disorder, depression or anxiety. But no gene has been shown to be a master switch.

The debate has raged for decades over whether mental illnesses sprout from nature or nurture. Scientists now suspect both. A new field linking genes and environment may chart the way for solving some of the mysteries shrouding mental illness.

Genes alone can only explain a few of the reasons people contract mental illnesses, become addicts or have developmental disorders, such as autism. Identical twins share a genetic makeup, so if genes controlled psychiatric disorders, whenever one twin developed a mental illness, the other would too. But that's not how it happens. Depending on the disorder, both twins develop it only about half the time. "We know the genetic risk of mental illness is about 50 percent, which leaves a whole other 50 percent unaccounted for," says Eric J. Nestler of the University of Texas Southwestern Medical Center at Dallas.

Some people say nurture, that is, "environment," is the root of psychiatric disorders, or at the very least accounts for the remainder of the risk. But no one has ever pinpointed exactly which experiences, infections, chemical exposures. types of stress or other environmental factors tip some brains into mental illness while others remain healthy despite the same insults, Akbarian says.

Scientists have also long sought explanations for why psychiatric disorders are so enduring, coming on slowly and then waxing and waning throughout life, or plunging addicts into craving, years after they've stopped taking drugs. Even the medications used to treat depression take weeks to grant relief.

The emerging field of epigenetics (which means "beyond genes") lies at this interface between genetics and environment and is revealing what marketers and Hollywood types have known for ages--that packaging is important.

Epigenetics is elucidating how environmental cues make their marks on genes. Such discoveries could help in understanding the mentally ill mind and lead to new treatments for psychiatric disorders and addiction.

Changing and not forgetting

EPIGENETIC MECHANISMS ALTER HOW cells use genes but don't change the DNA code in the genes themselves. The term "epigenetic" has been used for 60 years to describe the changes an organism experiences as it develops, but it has recently come to refer to the dozens of different modifications that DNA and its associated proteins undergo. All of the alterations essentially perform the same job: packaging genes properly.

Some of the modifications package genes so that they are shrink-wrapped tighter than a brand new CD, and just as hard to get into. Other epigenetic changes give cellular machinery easy access to genes. The ultimate effect is to finely tune to what degree a gene is turned on or off. Often the fine tuning is long-lasting, setting the level of a gene's activity for the lifetime of the cell.

Such extra-genetic programming is essential for cells to establish and maintain their identities throughout life. …

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