Testosterone in Healthy Men Increases Their Brains’ Response to Threat

Anew study in Biological Psychiatry reports on a neural circuit for maleaggression

Philadelphia, PA, August 11, 2014

Testosterone, a steroid hormone, is well known to contribute to aggressive behavior in males, but the neural circuits through which testosterone exerts these effects have not been clear.

Prior studies found that the administration of a single dose of testosterone influenced brain circuit function. Surprisingly, however,these studies were conducted exclusively in women.

Researchers, led by Dr. Justin Carré, sought to rectify this gap by conducting a study of the effects of testosterone on the brain's response to threat cues in healthy men.

They focused their attention on brain structures that mediate threat processing and aggressive behavior, including the amygdala, hypothalamus,and periaqueductal gray.

The researchers recruited 16 healthy young male volunteers, who completed two test days on which they received either testosterone or placebo. On both testing days, the men first received a drug that suppressed their testosterone. This step ensured that testosterone levels were similar among all study participants. The amount of testosterone administered in this study only returned testosterone levels to the normal range. Subjects then completed a face-matching task while undergoing a functional magnetic resonance imaging scan.

Data analyses revealed that, compared with placebo,testosterone increased reactivity of the amygdala, hypothalamus andperiaqueductal grey when viewing angry facial expressions.

"We were able to show for the first time that increasing levels of testosterone within the normal physiological range can have a profound effect on brain circuits that are involved in threat-processing and human aggression," said Carré, Assistant Professor at Nipissing University.

"Understanding testosterone effects on the brain activity patterns associated with threat and aggression may help us to better understand the 'fight or flight' response in males that may be relevant to aggression and anxiety," commented Dr. John Krystal, Editor of Biological Psychiatry.

Expanding our knowledge of exactly how testosterone affects the male brain is particularly important, as testosterone augmentation has become increasingly promoted and aggressively marketed as a solution to reduced virility in aging men. Further work is indeed continuing, Carré said. "Our current work is examining the extent to which a single administration of testosterone influences aggressive and competitive behavior in men."

The article is "Testosterone Rapidly Increases Neural Reactivity to Threat in Healthy Men: A Novel Two-Step Pharmacological Challenge Paradigm" by Stefan M.M. Goetz, Lingfei Tang, Moriah E. Thomason, Michael P.Diamond, Ahmad R. Hariri, and Justin M. Carré (DOI:10.1016/j.biopsych.2014.01.016). The article appears in Biological Psychiatry, Volume 76, Issue 4 (August 15, 2014), published by Elsevier.

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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 Justin M. Carré at justinca@nipissingu.ca.

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 infields 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 135 Psychiatry titles and 14th out of 251 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2013 Impact Factor score for Biological Psychiatry is 9.472.

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+1 214 648 0880
Biol.Psych@utsouthwestern.edu