Philadelphia, PA, February 2, 2016 - A new study by Neil Harrison and colleagues published in Biological Psychiatry suggests that a brain reward center, the striatum, may be directly affected by inflammation and that striatal change is related to the emergence of illness behaviors.

Inflammation increases the risk for depression. More specifically, inflammation induces behavioral changes similar to depression that are often associated with illness, including fatigue, difficulty concentrating, lack of motivation, and reduced experience of pleasure.

The authors recruited 23 patients with hepatitis C who were beginning treatment with interferon-alpha (INF-α). This treatment provokes an immediate inflammatory response, confirmed by measuring cytokines in the blood.

Four hours after INF-α administration, a specialized type of imaging, called magnetization transfer imaging, was performed that showed evidence of microstructural changes in the striatum when compared to scans conducted prior to INF-α administration. This suggests that the striatum is highly sensitive to IFN-α.

IFN-α also induced fatigue and depression in the patients, particularly over weeks 4 through 12 of treatment. Interestingly, the early striatal structural change predicted the later emergence of fatigue, but not depression, in the study participants.

Changes in the striatum were heterogeneous with some changes associated with the risk for fatigue, while other changes seemed to be protective against developing fatigue.

"Inflammation-related fatigue and depression are big clinical problems," said Dr. John Krystal, Editor of Biological Psychiatry. "This study highlights that the brain regions central to reward and motivation are directly altered by inflammation in ways that that appear to predispose or protect against developing fatigue but not depression. The heterogeneous striatal response may suggest that fatigue and mood are supported by different microcircuits within the striatum."

"These findings are important as they show that a relatively simple MRI technique can be used to measure effects of inflammation on the brain," Harrison commented. "Inflammation is increasingly implicated in the cause of common mental illnesses, particularly depression. This technique could be a powerful way to identify patients who are most sensitive to effects of inflammation on the brain. It could also be used to monitor response to novel anti-inflammatory therapies that are now being tested in depression."

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The article is "Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue" by Nicholas G. Dowell, Ella A. Cooper, Jeremy Tibble, Valerie Voon, Hugo D. Critchley, Mara Cercignani, and Neil A. Harrison (doi: 10.1016/j.biopsych.2015.05.015). The article appears in Biological Psychiatry, Volume 79, Issue 4 (February 15, 2016), 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 Neil Harrison at +44 (0)1273 87 6657 or n.harrison@bsms.ac.uk.

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, Chief of Psychiatry at Yale-New Haven Hospital, 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 6th out of 140 Psychiatry titles and 10th out of 252 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2014 Impact Factor score for Biological Psychiatry is 10.255.

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