Schizophrenia: It's in the wiring of the brain

Reports new study in Biological Psychiatry

2013-09-16

(Press-News.org) Philadelphia, PA, September 16, 2013 – Just as wires must be insulated to effectively carry electrical impulses, nerve cells must be insulated by myelin to effectively transmit neural impulses. Using typical magnetic resonance imaging or MRI, one can visually distinguish parts of the brain that look white and parts that look gray. Myelin is most prevalent in the white matter because this component of the brain tissue is principally comprised by the nerve cell projections (axons) that are covered by myelin and that transmit information from one part of the brain to another.

In a new paper in Biological Psychiatry, Fei Du and colleagues at Harvard Medical School combined two types of brain imaging to characterize abnormalities in the white matter in schizophrenia.

One type of imaging, called magnetic resonance spectroscopy, measures the levels of particular chemicals in the brain. Another approach, called magnetization transfer imaging, is sensitive to changes in the level of myelin in the white matter.

"The notion that the brain in schizophrenia is characterized by abnormalities in connections between distant brain regions is not new, and imaging studies using diffusion tensor imaging have long suggested that the white matter where these connections travel is abnormal in this condition," explained senior author Dr. Dost Öngür. "However, we have not had the tools to determine whether the abnormalities are in axons, or the myelin sheath around the axons, or both."

The researchers found evidence for abnormalities in both myelin and axons among patients with schizophrenia, when compared with healthy individuals who underwent the same testing. More specifically, they found reduced myelination of white matter pathways in schizophrenia, and also abnormal diffusion of N-acetylaspartate, a metabolite thought to be predominately localized within nerve cells.

This pattern of results is indicative of abnormalities in information processing and cognitive deficits, which is consistent with what scientists already know about how the brain is impacted by schizophrenia and the symptoms associated with this disorder.

"This study provides new evidence that myelination abnormalities in schizophrenia are associated with disturbances in the functional integrity of the white matter. As the white matter carries long range communication in the brain, the current findings raise new questions about the functional impact and treatment for these neural deficits," said Dr. John Krystal, Editor of Biological Psychiatry.

These findings are important because they suggest that "the white matter abnormalities in schizophrenia are complex and interconnected", added Öngür. "A strategy to impact both axonal health and myelin synthesis may be needed to restore normal white matter functioning in this condition."

Such a strategy to restore abnormal functioning is not likely in the near future, but advances provided by this study and others like it help bring scientists ever closer to that ultimate goal.

### The article is "Myelin and Axon Abnormalities in Schizophrenia Measured with Magnetic Resonance Imaging Techniques" by Fei Du, Alissa J. Cooper, Thida Thida, Ann K. Shinn, Bruce M. Cohen, and Dost Öngür (doi: 10.1016/j.biopsych.2013.03.003). The article appears in Biological Psychiatry, Volume 74, Issue 6 (September 15, 2013), published by Elsevier.

Notes for editors Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Dr. Dost Öngür at +1 617 855 3922 or dongur@partners.org.

The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 4th out of 135 Psychiatry titles and 13th out of 251 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2012 Impact Factor score for Biological Psychiatry is 9.247.

About Elsevier Elsevier is a world-leading provider of scientific, technical and medical information products and services. The company works in partnership with the global science and health communities to publish more than 2,000 journals, including The Lancet and Cell, and close to 20,000 book titles, including major reference works from Mosby and Saunders. Elsevier's online solutions include ScienceDirect, Scopus, SciVal, Reaxys, ClinicalKey and Mosby's Suite, which enhance the productivity of science and health professionals, helping research and health care institutions deliver better outcomes more cost-effectively.

A global business headquartered in Amsterdam, Elsevier employs 7,000 people worldwide. The company is part of Reed Elsevier Group PLC, a world leading provider of professional information solutions in the Science, Medical, Legal and Risk and Business sectors, which is jointly owned by Reed Elsevier PLC and Reed Elsevier NV. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

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Schizophrenia: It's in the wiring of the brain

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