New Study Replicates Association Between Genetic Variation and Antidepressant Treatment Response

New study published in Biological Psychiatry

Philadelphia, PA, July 15, 2008 – Pharmacogenetics, the study of genetic variation that influences an individual’s response to drugs, is an important and growing focus in all of medical research, including psychiatry. It is a complex field, however, revealed by the lack of consistent and replicable findings across multiple studies, but some encouraging results are beginning to emerge. A new study scheduled for publication in the June 15th issue of Biological Psychiatry evaluated genetic markers in the treatment response of antidepressants and this work implicates the same markers as found in a prior trial.

Lekman and colleagues, using clinical data and DNA samples from the largest depression treatment study to date, the STAR*D study, compared individual treatment response (the reduction or remission of depressive symptoms) to individual genotypes. The researchers found that certain markers, or variations, in the FKBP5 gene are associated with treatment response to citalopram, a widely used antidepressant drug. In other words, patients with a particular genotype tended to respond better to the antidepressant treatment than others. Silvia Paddock, Ph.D., corresponding author on this article, further explains: “Our results are encouraging, because they support earlier findings by a German group implicating the same gene. It is promising to see the same genetic markers to be associated with response in hospitalized patients in the German study, as well as non-hospitalized patients in our study.”

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, explains some background of this important gene: “FKBP5 is a gene that codes for a protein that influences the molecular actions of a class of stress hormones, the glucocorticoids. In prior studies, variation in this gene was associated with the emergence of dissociative symptoms in traumatized children and PTSD symptoms in adults who had been maltreated as children.” Childhood maltreatment has been previously reported to be a predictor of poor response to some antidepressants. Now that this current report has also implicated variation in the FKBP5 gene as related to antidepressant response, he adds that “we now need to close this apparent ‘loop,’ i.e., we need to understand how, at a molecular level and in the context of the developing brain, FKBP5 links childhood maltreatment and antidepressant response.” Dr. Paddock agrees that further research is necessary, noting that it’s needed “in order to confirm our results in further samples and understand the mechanism by which the genetic markers influence the chance of a depressed patient to respond to an antidepressant. This will, ultimately, allow us to develop new and better treatment strategies."

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Notes to Editors:
The article is “The FKBP5-Gene in Depression and Treatment Response—an Association Study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort” by Magnus Lekman, Gonzalo Laje, Dennis Charney, A. John Rush, Alexander F. Wilson, Alexa J.M. Sorant, Robert Lipsky, Stephen R. Wisniewski, Husseini Manji, Francis J. McMahon and Silvia Paddock. Drs. Lekman and Paddock are affiliated with the Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. Drs. Paddock, Laje and McMahon are associated with the Genetic Basis of Mood & Anxiety Disorders, Mood & Anxiety Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Department of Health & Human Services (DHHS), Bethesda, Maryland. Dr. Manji is with the Laboratory of Molecular Pathophysiology, Mood & Anxiety Program, NIMH, NIH, DHHS, Bethesda, Maryland. Drs. Wilson and Sorrant are affiliated with the Genometrics Section, Inherited Disease Research Branch, National Human Genome Research Institute, NIH, DHHS, Baltimore, Maryland. Dr. Lipsky is with the Section of Molecular Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse & Alcoholism, NIH, DHHS, Rockville, Maryland. Dr. Charney is associated with the Department of Psychiatry, Neuroscience, and Pharmacology & Biological Chemistry, Mount Sinai School of Medicine, New York, New York. Dr. Rush is with the Departments of Clinical Sciences and Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas. Dr. Wisniewski is affiliated with the Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania. The article appears in Biological Psychiatry, Volume 63, Issue 12 (June 15, 2008), published by Elsevier.

The authors’ disclosures of financial and conflicts of interests are available in the article. Dr. Krystal's disclosures of financial and conflicts of interests are available here.

Full text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at (215) 239-3674 or ja.dawkins@elsevier.com to obtain a copy or to schedule an interview.

About Biological Psychiatry
This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

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