Alcoholism and Other Addictions Research
History of the Mayo Clinic Samuel C. Johnson Genomics of Addictions Research Program
This program was established in 2004 by a generous gift from the Samuel C. Johnson Foundation aiming to identify genetic causes of alcoholism and develop individualized treatments. David Mrazek, M.D., immediate past chair of the Department of Psychiatry & Psychology and founding director of this program, formed a team with Joanna M. Biernacka, Ph.D., Doo-Sup Choi, Ph.D., Mark A. Frye, M.D., and Victor M. Karpyak, M.D., Ph.D., to achieve the goals. This program has led to the development of a new electronic database that captures key clinical characteristics of all patients with addictions at Mayo Clinic. Additionally, a DNA repository for patients with addictions was developed. New funding streams from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Mayo Center for Individualized Medicine have allowed this research to expand beyond genomics into translational science with a focus on individualized medicine.
The Mayo Clinic Program for the Individualized Treatment of Alcohol Dependence
The S.C. Johnson research team was awarded a P20 developmental center grant from the National Institute on Alcohol Abuse and Alcoholism to establish the Center for Individualized Treatment of Alcohol Dependence (CITA). The primary goal of the funded research was to develop infrastructure for an expanding research team dedicated to designing and launching systematic pharmacogenomic studies of pharmacological treatments for alcoholism, initially focused on the medication acamprosate, an FDA-approved medication for treating alcoholism.
The grant has funded the creation of an expanded multidisciplinary team of investigators who work together to design and conduct preclinical and clinical studies to identify which alcohol-dependent patients are most likely to benefit from acamprosate.
Center for the Individualized Treatment of Alcohol Dependence and Co-Morbid Depression (CITA-D)
With the successful implementation of the National Institutes of Health-supported P20 Center, Mayo S.C. Johnson investigators have published approximately 40 articles, including 25 peer-reviewed research articles in major journals during the last three years in the field of addiction, neuroscience, genetics and psychiatry. In addition, the investigators have established national and international collaborations and expanded their research areas to comorbid psychiatric disorders including depression, bipolar disorders and eating disorders.
Alcohol dependence and major depressive disorder have been identified as two of the most serious public health problems. The development of depression in a patient with alcohol dependence is a major risk factor for adverse outcomes including relapse and suicide. Currently, the research team is working toward individualizing pharmacological treatment in patients with alcohol dependence and comorbid depression by the identification of pharmacogenomic and pharmacometabolomic biomarkers that predict treatment response.
Animal models also are being used to examine preclinical biomarkers and validate function of the clinical biomarkers. The long-term goal of the research program is to translate and integrate these clinical and preclinical discoveries to clinical settings to individualize treatments designed for patients based on their genomic and metabolomic profiles.
Alcoholism and Other Addictions investigators
S.C. Johnson investigators
As the statistical geneticist in the Samuel C. Johnson Genomics of Addiction Program and an investigator in the NIAAA-funded Mayo Clinic Center for Individualized Treatment of Alcohol Dependence (CITA), Dr. Biernacka assists with designing studies and analyzing the resulting data. These studies are aimed at elucidating the complex relationships between particular genetic variants and traits, such as increased risk of developing alcoholism or increased likelihood of responding to a specific treatment. As these types of analyses require the application of advanced statistical techniques, Dr. Biernacka also works on the development of novel methods for the analysis of genetic data. Her research is currently focused primarily on gene-set analysis and methods for detection of gene-gene interactions.
Dr. Choi's research has identified several molecular and biological mechanisms underlying alcohol abuse and addiction with the goal of developing new treatment methods. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) P20 grant has enabled the establishment of an effective research program to identify biomarkers for the creation of individualized treatments for alcohol use disorders.
Dr. Frye has made significant advances in the understanding of the neurobiology of cravings and mood disorders comorbidity with alcohol dependence. Findings of gender differences in alcohol cravings and depressive symptoms have recently been published. Further studies of how these clinical differences relate to differential treatment response are under way.
Dr. Karpyak serves as the principal investigator of the pharmacogenomic probe study of acamprosate, and has been responsible for the recruitment and follow-up evaluations of more than 300 alcohol-dependent subjects. This project will allow Dr. Karpyak and his team to identify genetic predictors associated with the response to acamprosate, which can be used to guide clinical decisions.
Over the course of his career, Dr. David Mrazek has been interested in defining how genetic variation influences both vulnerability to psychopathology and response to treatment. For the past decade, Dr. Mrazek has led the Department of Psychiatry & Psychology at the Mayo Clinic and has worked in close collaboration with both the Department of Laboratory Medicine & Pathology and the Department of Molecular Pharmacology and Experimental Therapeutics to better define the relationship between pharmacokinetic and pharmacodynamic gene variations and medication response.
See the Mayo Clinic Samuel C. Johnson Program in the Genomics of Addiction 2011 Annual Report, including a full list of publications.
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