Gene 'has key schizophrenia role'

Two studies have pinpointed a single gene as key to the development and treatment of schizophrenia.

A US team from the Howard Hughes Medical Institute found that a mutated version of the DISC1 gene disrupts the growth and development of brain cells.

And a team from the University of Edinburgh showed that the gene affects how patients respond to treatment.

Both studies, published in the journals PLoS One and Cell, raise hopes of more effective treatment for schizophrenia.

DISC1 GENE

• Linked in the early 1990s to mental illnesses prevalent in a large Scottish family
• Over five generations many family members had developed schizophrenia, bipolar disorder, and other mood disorders
• Each family member diagnosed with mental illness also carried a mutated copy of DISC1

The condition is a common form of mental illness, affecting up to 1% of adults worldwide.

Symptoms tend to appear in late adolescence or early adulthood, and can include delusions, hallucinations, paranoia, and depression.

The US team showed that DISC1 plays a key role in normal brain development and the growth of individual neurons. However, carrying the wrong version of the gene can make this process go awry.

Working on mice, they showed that DISC1 was active, both in cells taken from embryos and in brain stem cells taken from adult mice.

When DISC1 levels were reduced in adult mice their brain cells failed to divide, and the animals developed symptoms mimicking schizophrenia in humans.

Further tests showed that DISC1 acts like lithium, a drug commonly prescribed as mood stabiliser to patients with mental illness, inhibiting the action of a key chemical in the brain.

When mice with depressed levels of DISC1 were treated with this chemical, their symptoms began to improve.

Lead researcher Dr Li-Heui Tsai said: "We need to get a handle on the genetics of schizophrenia, but now we know how DISC1 probably contributes to the disorder, which is a big step."

Impact on treatment

The Edinburgh researchers analysed data generated by the Human Genome Project, set up to decode the complete genetic blueprint of humans.

They showed DISC1 affects a number of other genes current medications are designed to target.

Dr William Hennah, who led the Edinburgh team, said: "We know that disorders such as schizophrenia have a genetic element and that this specific gene, DISC1, is important to that process.

"This research helps us to understand exactly how it affects brain development and provides clues about how to solve problems when that process goes wrong."

The charity Rethink, which campaigns on severe mental health issues, described the research as an important step forward in understanding schizophrenia - but only a small step.

A spokesperson said: "With mental illness receiving just 6.5% of research funding in the UK, we can expect it to be a very long time before these findings are developed into major breakthroughs.

"If we really want to unravel the complex causes of schizophrenia and deliver more effective treatments we need a level of research investment proportionate to the enormous human and economic costs of the illness."

RELATED INTERNET LINKS
Howard Hughes Medical Institute
Cell
University of Edinburgh
PLoS One
Rethink
SANE
Headroom: Schizophrenia
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