Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Collaborations yield new discoveries in psychiatric genetics


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:

More articles from Life Sciences:

nachricht International team discovers novel Alzheimer's disease risk gene among Icelanders
24.10.2016 | Baylor College of Medicine

nachricht New bacteria groups, and stunning diversity, discovered underground
24.10.2016 | DOE/Lawrence Berkeley National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

New method increases energy density in lithium batteries

24.10.2016 | Power and Electrical Engineering

International team discovers novel Alzheimer's disease risk gene among Icelanders

24.10.2016 | Life Sciences

New bacteria groups, and stunning diversity, discovered underground

24.10.2016 | Life Sciences

More VideoLinks >>>