Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Collaborations yield new discoveries in psychiatric genetics

10.10.2005


Two New Jersey research teams are reporting discoveries about the biological nature of psychiatric disorders that may bring them closer to the ultimate goal of finding cures for complex diseases, such as autism and schizophrenia.



Scientists at Rutgers, The State University of New Jersey, in collaboration with colleagues at the University of Medicine and Dentistry of New Jersey (UMDNJ) have unveiled new information regarding the genetic, cellular and neurological bases of susceptibility to these diseases.

Using data drawn from the Rutgers Cell and DNA Repository on 518 families, each with multiple autistic children, James Millonig and Linda Brzustowicz, assisted by Emanuel DiCicco-Bloom, led a team that further substantiates the link between autism and Engrailed 2 (EN2), a gene important in central nervous system development. Their research is presented in the November issue of the American Journal of Human Genetics (AJHG).


Millonig and Brzustowicz had previously demonstrated an association with the gene in a sample of 167 families with autism. The new study adds another 351 families and now provides convincing statistical support for the existence of a mutated form of EN2 that increases the risk for autism. The statistics also showed EN2 may contribute to up to 40 percent of autism cases in the general population.

EN2 is involved with the development of the cerebellum, the part of the brain that governs movement and, to some extent, language and speech. A change in EN2 could potentially produce symptoms of autism. Further work on characterizing EN2 and on the identification of additional autism susceptibility genes will be funded by a $2.3 million grant to Millonig and DiCicco-Bloom and a linked $2.5 million grant to Brzustowicz from the National Institute of Mental Health (NIMH) to identify additional autism susceptibility genes.

Millonig is an assistant professor of neuroscience and cell biology at UMDNJ-Robert Wood Johnson Medical School (RWJMS) and an adjunct assistant professor in Rutgers’ department of genetics. He is also a resident faculty member of the Center for Advanced Biotechnology and Medicine, a research enterprise jointly operated by both institutions. Brustowicz is a professor of genetics at Rutgers, a board certified psychiatrist and an associate professor of psychiatry at the UMDNJ-New Jersey Medical School; DiCicco-Bloom is a professor of neuroscience and cell biology at UMDNJ-RWJMS.

A second team led by Brustowicz and Bonnie Firestein, an assistant professor in Rutgers’ department of cell biology and neuroscience, implicated a gene called CAPON in schizophrenia. A report of their research is available in the online journal PLoS (Public Library of Science) Medicine.

CAPON had been previously identified as a gene involved in the processes of communication between neurons in the brain. The Rutgers team identified a new variant of the CAPON gene that produces a shorter protein product. Using a sample of post-mortem brains, the researchers found elevated levels of this variant in the brains from individuals with schizophrenia and bipolar disorder. Brzustowicz and Firestein also offered their conclusions about how CAPON operates in its signaling context, functional evidence supporting the connection between the gene and these psychiatric diseases.

Researchers agree that there are environmental contributors to susceptibility to psychiatric disorders, but based on inheritance patterns of these diseases seen in families, the genetic component appears to be quite strong. The inheritance picture, however, is far from clear. It is not like the simple, one-gene models for eye color or blood type or found in such diseases as muscular dystrophy or cystic fibrosis.

"The diseases we study are polygenic, meaning that many genes are likely to contribute, but how many genes there are and how they interact are unknowns," Millonig said. "Identifying a gene in a complex disease may give more insight into the pathways involved – it helps you begin to unravel what is at its basis."

Earlier genetic studies of a Canadian study population of large families with a high incidence of schizophrenia pointed the way to CAPON. The gene was known to code for a protein that functioned in a neuronal pathway thought to be linked to schizophrenia. Beyond establishing a mere statistical connection between a gene and a psychiatric disorder – CAPON and schizophrenia – Firestein and Brzustowicz provided functional evidence as to the nature of the connection. "We began with a purely genetic approach and identified a region of chromosome 1 that seemed very likely to contain a susceptibility gene, but then moved on to studies of gene expression in human brains to search for convincing evidence of a functional role for CAPON in schizophrenia," Brzustowicz said.

The researchers discovered two forms of the gene are normally expressed in human brain, a long form and a short form. Based on what is known about the gene interactions, it is predicted that when the short form is present in excess, it will disrupt the signaling pathway, resulting in decreased function, reduced signaling and less communication, all of which are suspected to occur in schizophrenia, Firestein said. The published information includes a detailed description of how this is thought to occur.

The research team then analyzed the post-mortem brains – 35 from individuals with schizophrenia, 35 from bipolar individuals and 35 from those with normal brains – and found significantly increased levels of the short form in the specimens from individuals with psychiatric disorders.

While many genes have been implicated in schizophrenia based on family studies, there has been little functional evidence for alteration in the proteins that are actually involved, but with CAPON there does, indeed, appear to be functional evidence.

"If CAPON really does disrupt this cellular pathway so the neurons cannot signal when and where they are supposed to, there is a point of entry for therapeutics," Firestein said. "While we can’t make the therapeutics right now, we may have established some targets."

Joseph Blumberg | EurekAlert!
Further information:
http://www.rutgers.edu

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>