Schizophrenia risk is increased with a particular gene mutation

An article posted on February 23rd by the Los Angeles Times:

By Shari Roan

Schizophrenia is a severe, complicated illness. There are no obvious explanations for what causes the condition, which causes hallucinations and delusions. Genes are known to play a big role. The condition is often clustered in families.

Scientists announced a significant step in understanding the genetics of the disease this week. A large nationwide consortium of scientists led by Jonathan Sebat of UC San Diego has identified a gene mutation that is strongly linked to the disorder. Understanding the signaling pathway of this mutation creates a target for future therapies.

Previous research has shown a number of rare gene mutations that increase the risk of schizophrenia. In the new study, researchers looked for specific gene variants, called copy number variants, in 8,290 people with schizophrenia and 7,431 healthy people. Among the discoveries was a duplication in the tip of chromosome 7q. This duplication was found in people with schizophrenia at a rate 14 times that of healthy people.

The duplication affects a particular gene called the vasoactive intestinal peptide receptor 2 gene, which is known to play a role in behavior and learning. In people with schizophrenia, the expression of this gene is much higher, the researchers found. The VIPR2 gene mutation, therefore, will be an important target in developing medications that might alter the symptoms of the illness.

"This discovery might be the best target yet to come out of genetic studies of mental illness," Sebat said in a new release. The research was published online in the journal Nature.

Image courtesy of the National Library of Medicine.

Combating schizophrenia

Nature, one of the most prestigious science journals in the world, devotes its November 11th edition to schizophrenia:

Research has revealed daunting complexities in the psychiatric condition, but also new routes towards diagnosis and treatment.

A special collection of articles focuses on the challenges of schizophrenia, from spotting early symptoms during adolescence to changing the stigma associated with the disease.

Editorial

Combating schizophrenia
Research has revealed daunting complexities in the psychiatric condition, but also new routes towards diagnosis and treatment.

News

China tackles surge in mental illness
Psychological examinations added to selection procedure for government officials.

Features

The making of a troubled mind
Schizophrenia appears during adolescence. But where does one begin and the other end?

The drug deadlock
The biology is too complicated. Pharma companies are quitting. Where are schizophrenia drugs going to come from?

Comment

Short-lived campaigns are not enough
The stigma of mental illness will be reduced only if region-specific awareness initiatives become a permanent fixture of health and social services, argues Norman Sartorius.

Cognitive remediation therapy needs funding
More rigorous studies should be done on the effects of a therapy that seems to improve the everyday functioning of people with schizophrenia, says Til Wykes.

In retrospect: The five lives of the psychiatry manual
Roy Richard Grinker describes the military origins of the key reference work for diagnosing mental illness.

Audio

Nature podcast (24:36, Rethinking schizophrenia)
Thomas Insel, director of the National Institute of Mental Health, and Til Wykes, psychiatrist at Kings College London, talk about the symptoms, causes and best treatments for schizophrenia.

Perspectives

Rethinking schizophrenia
Thomas Insel, director of the National Institute of Mental Health, calls for schizophrenia to be emphasized as a neurodevelopmental disorder in which psychosis is a late — and potentially curable — stage.

From maps to mechanisms through neuroimaging of schizophrenia
Andreas Meyer-Lindenberg, director of the Central Institute of Mental Health, Mannheim, explains how neuroimagng and other systems-level techniques can help develop future treatment.

The environment and schizophrenia
Jim van Os, Gunter Kenis and Bart Rutten review our knowledge of the environmental factors that influence schizophrenia risk, and the major challenges that will be involved in teasing them out.

Image credit: The cover artwork is by Rodger Casier and NARSAD Artworks, a non-profit organization that showcases artists with mental illness. Proceeds from the art go to the research-funding body NARSAD.

Identification of a serotonin/glutamate receptor complex implicated in psychosis

Medical News TODAY
Article Date: 25 Feb 2008

Mount Sinai researchers have identified a new receptor complex in the brain that responds to several types of antipsychotic drugs used to treat schizophrenia and also reacts to hallucinogenic drugs such as LSD (molecular structure illustrated above). Stuart Sealfon, MD, Professor of Neurology and Director of the Center for Translational Systems Biology at Mount Sinai School of Medicine and colleagues discovered the receptor complex, which could help provide new treatments for schizophrenia and other diseases associated with psychosis. This new study was published online in Nature.

"The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. The discovery of this receptor complex could provide a new target for developing drugs to treat schizophrenia," said Dr. Sealfon.

The study done in mice identified that the two receptors, [for the] neurotransmitters glutamate and serotonin, interact and work as a hybrid complex. Hallucinogenic drugs, such as LSD and psilocybin, act at serotonin receptors to cause responses similar to some of the core symptoms of schizophrenia. The researchers showed that the glutamate receptor interacts with the serotonin receptor to form functional complexes in brain cortex. This receptor complex triggers unique cellular responses when targeted by hallucinogenic drugs.

Activation of the glutamate receptor blocks hallucinogen-specific signaling and changes behavioral responses in mice.

In untreated [individuals living with schizophrenia], the serotonin receptor is up-regulated and the glutamate receptor is downregulated, a pattern that could predispose to psychosis. These findings suggest that the newly identified serotonin/glutamate complex may be involved in the altered cortical processes of schizophrenia.

"The findings further our understanding of how hallucinations occur. They suggest a brain abnormality that may contribute to the abnormal brain function in schizophrenia," said Dr. Sealfon. "We can now use this information to do further study and hopefully develop more specific drug therapies for treating patients who suffer from hallucinations and psychosis."

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation's oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 50,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.

Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants.

Mount Sinai Medical Center
One Gustave Levy Place
New York, NY 10029
United States
www.mountsinai.org