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PUBLIC RELEASE DATE:
8-Jul-2013

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Contact: Rhiannon Bugno
Biol.Psych@utsouthwestern.edu
214-648-0880
Elsevier
@elseviernews

Brain structural deficits may contribute to increased functional connections

Reports new study in Biological Psychiatry

Philadelphia, PA -- Major depressive disorder is associated with a dysregulation of brain regions including the prefrontal cortex and limbic system. The relationship between structural and functional abnormalities in these brain regions in depressed patients is far from clear. However, both types of changes are assumed to underlie the symptoms of this disorder.

This lack of understanding prompted Dr. Bart de Kwaasteniet at the Academic Medical Center in Amsterdam and his colleagues to use a multimodal neuroimaging approach to further investigate this relationship.

The researchers, led by Professor Damiaan Denys, recruited 18 patients with major depressive disorder and 24 healthy individuals, all of whom underwent multiple neuroimaging scans. They specifically focused on the structural and functional connectivity between the subgenual anterior cingulate cortex (ACC) and the medial temporal lobe, two regions that are connected by a white matter tract called the uncinate fasciculus. These regions are known to be involved in the regulation of emotion and memory.

de Kwaasteniet explained their findings: "We identified decreased structural integrity of the uncinate fasciculus connecting the medial temporal lobe and the subgenual ACC. Furthermore, we identified an increased functional connection between these regions in major depression relative to controls. Importantly, we identified a negative correlation between the integrity of this white matter tract and the functional connection between the subgenual ACC and bilateral hippocampus in major depression."

These results suggest that structural disturbances in the uncinate fasciculus contribute to abnormally high functional interactions among brain circuits associated with the symptoms of depression. "This leads to the hypothesis that abnormalities in brain structure lead to differences in connectivity between brain areas in depressive disorder," added de Kwaasteniet.

However, they also hypothesized that the reverse may be true as well. In other words, that the increased functional connectivity among these brain regions leads to structural changes in the brain's white matter fibers by means of an abnormally increased signal transduction. This hypothesis is supported by recent studies in schizophrenia which suggest that circuit hyperactivity may be a predictor of subsequent cortical atrophy.

"This interesting study suggests that abnormalities in the structural connections between brain regions, the white matter, are associated with abnormal activity within a brain circuit implicated in the symptoms of depression. This observation raises an important question about the implications of treating the circuit functional abnormalities without fixing the underlying brain structure," commented Dr. John Krystal, Editor of Biological Psychiatry. "Perhaps the structural abnormalities contribute to the risk for the relapse of depression among individuals whose brain circuit activity has responded to antidepressant medications."

More research will be necessary to test the theories generated from the findings of this study.

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The article is "Relation Between Structural and Functional Connectivity in Major Depressive Disorder" by Bart de Kwaasteniet, Eric Ruhe, Matthan Caan, Maaike Rive, Silvia Olabarriaga, Martine Groefsema, Lieke Heesink, Guido van Wingen, and Damiaan Denys (doi: 10.1016/j.biopsych.2012.12.024). The article appears in Biological Psychiatry, Volume 74, Issue 1 (July 1, 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 Bart de Kwaasteniet at +31 208913357 or b.p.dekwaasteniet@amc.nl.

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 5th out of 129 Psychiatry titles and 16th out of 243 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2011 Impact Factor score for Biological Psychiatry is 8.283.

About Elsevier

Elsevier is a world-leading publisher 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 SciVerse ScienceDirect, SciVerse Scopus, Reaxys, MD Consult and Nursing Consult, which enhance the productivity of science and health professionals, and the SciVal suite and MEDai's Pinpoint Review, which help 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 publisher and information provider, 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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