Featured Research

from universities, journals, and other organizations

Link Between Genetic Defect And Brain Changes In Schizophrenia Demonstrated

Date:
October 17, 2009
Source:
University of North Carolina School of Medicine
Summary:
Researchers have found that the 22q11 gene deletion -- a mutation that confers the highest known genetic risk for schizophrenia -- is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.

For decades, scientists have thought the faulty neural wiring that predisposes individuals to behavioral disorders like autism and psychiatric diseases like schizophrenia must occur during development. Even so, no one has ever shown that a risk gene for the disease actually disrupts brain development.

Now, researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion -- a mutation that confers the highest known genetic risk for schizophrenia -- is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.

In studies conducted in mice, the researchers discovered that the genetic lesion alters the number of a critical subset of neurons that end up in the brain's cerebral cortex -- the region critical to reasoning and memory. The defect also causes another type of nerve cell -- called GABAergic neurons -- to be misplaced within the brain's cortical layers, resulting in a subtle miswiring of the organ.

"For practically ever other disease, we know what cells take a hit," said senior study author Anthony LaMantia, Ph.D., professor of cell and molecular physiology and co-director of the Silvio M. Conte Center for Research in Mental Disorders at the UNC School of Medicine. "For multiple sclerosis the myelinating oligodendrocytes in the brain falter, for Lou Gehrig's disease the motor neurons in the brain stem degenerate. But we really had no idea what was happening in schizophrenia, or in any of the psychiatric diseases for that matter -- until now."

His study will be presented Oct. 17 at the Society for Neuroscience meeting in Chicago, by Daniel Meechan, Ph.D., post-doctoral fellow in the LaMantia laboratory and the first author of a recent paper in Proceedings of the National Academy of Sciences that details the findings.

The study lends the first clear support to the "neurodevelopmental hypothesis" -- a scientific theory LaMantia calls the "Hail Mary" of schizophrenia pathologists.

For many years, researchers searched in vain for any indication that the brains of patients with schizophrenia were different from normal subjects --for some laboratory finding along the lines of the plaques and tangles characteristic of Alzheimer's disease or the degeneration of dopamine cells that are the calling card of Parkinson's disease. Similar degenerative change has never been identified for schizophrenia. Finally they proposed that the defects in schizophrenia must arise before the brain is fully formed, rather than after.

Then researchers began to discover regions of the genome -- many of which had neurodevelopmental functions -- that made people susceptible to schizophrenia.

In this study, LaMantia and his colleagues decided to pursue deletion of one such region on human chromosome 22, which causes DiGeorge syndrome in humans, because it is the single best-defined genetic lesion associated with schizophrenia. They tracked two subclasses of neural stem cells -- called basal and apical progenitors -- throughout early brain development in a mutant mouse with the same genetic deletion. They found that the basal progenitors divided more slowly than they should, and as a result the cells that they give rise to in the cortex were not generated in the proper numbers.

The researchers also looked at another population of cells, the GABAergic cells that are thought to essentially put the brakes on electrical activity in mature cortical circuits. The function of these cells is believed to be one of last processes to be disrupted in the schizophrenic brain. LaMantia found that these GABAergic neurons never made their way to their correct positions in the cortical layers of the brain of the mouse model of DiGeorge Syndrome .

The researchers would now like to figure out how these alterations in the circuitry of the brain affect the behavior of the mouse. They also hope that understanding the "mis-wiring" of the brain in a genetic animal model of schizophrenia would help them understand the causes of the disease in the general population.

"Now that we know what cells can be affected in schizophrenia, it opens up new avenues in thinking about the molecular mechanisms underlying this and other psychiatric illnesses," said LaMantia. "We can even begin to look for biomarkers of the disease that can be used for better diagnosis and treatment."

Funding for the studies led at UNC came from the National Institutes of Health and the Silvio M. Conte Center. Study co-authors from LaMantia's laboratory at UNC include postdoctoral fellows Daniel W. Meechan, Erin S. Tucker and Thomas M. Maynard.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of North Carolina School of Medicine. "Link Between Genetic Defect And Brain Changes In Schizophrenia Demonstrated." ScienceDaily. ScienceDaily, 17 October 2009. <www.sciencedaily.com/releases/2009/10/091016112634.htm>.
University of North Carolina School of Medicine. (2009, October 17). Link Between Genetic Defect And Brain Changes In Schizophrenia Demonstrated. ScienceDaily. Retrieved September 24, 2014 from www.sciencedaily.com/releases/2009/10/091016112634.htm
University of North Carolina School of Medicine. "Link Between Genetic Defect And Brain Changes In Schizophrenia Demonstrated." ScienceDaily. www.sciencedaily.com/releases/2009/10/091016112634.htm (accessed September 24, 2014).

Share This



More Mind & Brain News

Wednesday, September 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Food Addiction Might Be Caused By PTSD

Food Addiction Might Be Caused By PTSD

Newsy (Sep. 18, 2014) New research shows that women who suffer from PTSD are three times more likely to develop a food addiction. Video provided by Newsy
Powered by NewsLook.com
Corporal Punishment on Decline, Debate Renews

Corporal Punishment on Decline, Debate Renews

AP (Sep. 16, 2014) Corporal punishment in the United States is on the decline, but there is renewed debate over its use after Minnesota Vikings running back Adrian Peterson was charged with child abuse. (Sept. 16) Video provided by AP
Powered by NewsLook.com
FDA Eyes Skin Shocks Used at Mass. School

FDA Eyes Skin Shocks Used at Mass. School

AP (Sep. 15, 2014) The FDA is considering whether to ban devices used by the Judge Rotenberg Educational Center in Canton, Massachusetts, the only place in the country known to use electrical skin shocks as aversive conditioning for aggressive patients. (Sept. 15) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins