Posttraumatic Stress Disorder Treatment: Genetic Predictor of Response to Exposure Therapy

 From a new study in Biological Psychiatry

Philadelphia, PA, June 11, 2013

There is growing evidence that a gene variant that reduces the plasticity of the nervous system also modulates responses to treatments for mood and anxiety disorders. In this case, patients with posttraumatic stress disorder, or PTSD, with a less functional variant of the gene coding for brain-derived neurotrophic factor (BDNF), responded less well to exposure therapy.

This gene has been implicated previously in treatment response. Basic science studies have convincingly shown that BDNF levels are an important modifier of the therapeutic effects of antidepressants in animal models. Other researchers have made similar findings in a small group of depressed patients treated with the rapid-acting antidepressant ketamine. Low BDNF plasma levels also have been linked to poorer effects of cognitive rehabilitation in schizophrenia. BDNF infused directly into the infralimbic prefrontal cortex in rats was found to extinguish conditioned fear, and BDNF levels were found to modulate the amount of fear extinction.

"Findings are accumulating to suggest that BDNF is an important modifier of the responses to a number of clinical interventions, presumably because BDNF is such an important regulator of neuroplasticity, i.e., the ability of the brain to adapt," said Dr. John Krystal, Editor of Biological Psychiatry.

In this study, researchers from Australia and Puerto Rico teamed up to investigate the influence of the BDNF Val66Met genotype on response to exposure therapy in patients with PTSD. They recruited 55 patients, all of whom participated in an 8-week exposure-based cognitive behavior therapy program.

Exposure therapy is currently the most effective treatment for PTSD, although it does not work for everyone. This type of therapy is delivered over multiple one-on-one sessions with a trained therapist, with a goal of reducing patients' fear and anxiety.

They found that patients with the Met-66 allele of BDNF, compared with patients with the Val/Val allele, showed poorer response to exposure therapy.

"This paper reflects an important and significant advance, in translating recent ground-breaking findings in animal and human neuroscience into clinically anxious populations," said first author Dr. Kim Felmingham.

She added, "Findings from this study support a widely held, but largely untested, hypothesis that extinction is necessary for exposure therapy. It also provides evidence that genotypes influence response to cognitive behavior therapy."

This finding supports prior evidence and highlights the importance of considering genotypes as potential predictor variables in clinical trials of exposure therapy.

The article is "The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Predicts Response to Exposure Therapy in Posttraumatic Stress Disorder" by Kim L. Felmingham, Carol Dobson-Stone, Peter R. Schofield, Gregory J. Quirk, and Richard A. Bryant (doi: 10.1016/j.biopsych.2012.10.033). The article appears in Biological Psychiatry, Volume 73, Issue 11 (June 1, 2013), 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 Kim Felmingham at Kim.Felmingham@utas.edu.au.

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 16thout of 243 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2011 Impact Factor score for Biological Psychiatryis 8.283.

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