Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors
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Department of Psychiatry, School of Medicine and McKnight Brain Institute, University of Florida, W University Ave., Gainesville, FL 32601, USA
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Department of Engineering Management Advanced Technology, Chang Jung Christian University, No. 396, Sec. 1, Changrong Road, Tainan 71101, Taiwan
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Department of Anatomy & Neurobiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA
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Department of Occupational Safety and Health, Chang Jung Christian University, No. 396, Sec. 1, Changrong Road, Tainan 71101, Taiwan
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Emeritus, Department of Physiology, University of Tennessee, 719 Andy Holt Tower, Knoxville, TN 37996, USA
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Unique Mindcare, Inc., 1900 Saint James Place, Houston, TX 77056, USA
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Department of Neurofeedback, Southeastern Biofeedback and Neurobehavioral Clinic, 101 Westwood Road, Knoxville, TN 37919, USA
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Department of Neuroscience & Population Genetics, EMMS Nazareth Hospital, Nazareth, Israel
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Department of Neurosurgery, Weill Cornell College of Medicine, 1300 York Ave., New York, NY 10065, USA
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Department of Academic Informatics Services, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
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Department of Nutrigenomics, LifeGen, Inc., P.O. Box 366, 570 Lederach Stattion Way, Lederach, PA 19450, USA
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Department of Genomic Research, Carlsbad Science Foundation, Department of Medical Genetics, City of Hope National Medical Center, 1500 Duarte Road, Duarte, CA 91010, USA
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Department of Kinesiology and Health Sciences, York University, 4700 Keele Street, Toronto, ON M3J 1P3, Canada
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Department of Integrative Medicine, PATH Medical Research Foundation, 304 Park Ave. South, New York, NY 10010, USA
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Hospital Universitario 12 de Octubre, Servicio de Psiquiatria, Av. Cordoba SN, Madrid 28041, Spain
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Department of Holistic Medicine, G&G Holistic Addiction Treatment, Inc., 1590 Northeast 162nd Street, North Miami Beach, FL 33162, USA
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Department of Research, National Institute for Holistic Addiction Studies, 1590 Northeast 162nd Street, North Miami Beach, FL 33162, USA
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Dominion Diagnostics, Inc., 211 Circuit Road, North Kingstown, RI 02852, USA
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Center for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India
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Meadows Edge Recovery Center, 580 10 Rod Road, North Kingstown, RI 02852, USA
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Authors to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2011, 8(12), 4425-4459; https://doi.org/10.3390/ijerph8124425
Received: 26 October 2011 / Revised: 23 November 2011 / Accepted: 23 November 2011 / Published: 29 November 2011
(This article belongs to the Special Issue Substance and Behavioral Addictions: Co-Occurrence and Specificity)
Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.
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Keywords:
dopamine; gene polymorphisms; generational association studies; phenotype; “super normal” controls; Reward Deficiency Syndrome (RDS)
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Blum, K.; Chen, A.L.C.; Oscar-Berman, M.; Chen, T.J.H.; Lubar, J.; White, N.; Lubar, J.; Bowirrat, A.; Braverman, E.; Schoolfield, J.; Waite, R.L.; Downs, B.W.; Madigan, M.; Comings, D.E.; Davis, C.; Kerner, M.M.; Knopf, J.; Palomo, T.; Giordano, J.J.; Morse, S.A.; Fornari, F.; Barh, D.; Femino, J.; Bailey, J.A. Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors. Int. J. Environ. Res. Public Health 2011, 8, 4425-4459.
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