Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards.
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2014-01-31
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BACKGROUND: There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). METHODS: The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. RESULTS: T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. CONCLUSIONS: This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation.
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Damiano, Cara R, Joseph Aloi, Kaitlyn Dunlap, Caley J Burrus, Maya G Mosner, Rachel V Kozink, Ralph Edward McLaurin, O'Dhaniel A Mullette-Gillman, et al. (2014). Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards. Mol Autism, 5(1). p. 7. 10.1186/2040-2392-5-7 Retrieved from https://hdl.handle.net/10161/12955.
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Scholars@Duke
Scott Huettel
Research in my laboratory investigates the brain mechanisms underlying economic and social decision making; collectively, this research falls into the field of “decision neuroscience” or "neuroeconomics". My laboratory uses fMRI to probe brain function, behavioral assays to characterize individual differences, and other physiological methods (e.g., eye tracking, pharmacological manipulation, genetics) to link brain and behavior. Concurrent with research on basic processes, my laboratory has also investigated the application of new analysis methods for fMRI data, including functional connectivity analyses, pattern classification analyses, and combinatoric multivariate approaches. We have also been applying computational methods to problems in behavioral economics and consumer decision making.
I have also been very active in outreach, mentorship, and educational activities; as examples, I am lead author on the textbook Functional Magnetic Resonance Imaging (Sinauer Associates; 3rd edition in 2014), I teach Fundamentals of Decision Science, Decision Neuroscience and Neuroethics, and many of my postdoctoral and graduate trainees now lead research laboratories of their own.
F Joseph McClernon
Joseph McClernon, Ph.D., is a professor in the Department of Psychiatry and Behavioral Sciences and founder/director of the Center for Addiction Science and Technology (CfAST). He is the Associate Director of the Duke Clinical and Translational Science Institute (CTSI). During his tenure with CTSI, his leadership has been critical to building a culture of evaluation and continuous improvement, in strengthening the institute’s partnership with North Carolina Central University and other regional partners, and in planning strategy and development for the institute.
Dr. McClernon earned a Ph.D. in clinical psychology in 2001 from Southern Illinois University-Carbondale and completed a postdoctoral fellowship at Duke in 2002. He served as Director of the Addiction Division in Psychiatry and Behavioral Sciences from 2012-2020. His research is focused on increasing our understanding of tobacco use, developing new and more effective interventions to treat nicotine dependence, and informing the FDA’s regulation of tobacco products. He has served as a site-PI and Co-I for more than ten years in the Center for the Evaluation of Nicotine in Cigarettes (CENIC)— a national consortium that has provided the bulk of evidence to the FDA for informing national policies that will reduce nicotine in cigarettes to non-addictive levels, thus saving millions of lives. Dr. McClernon is now leading efforts to transition CENIC’s focus to public health interventions that ensure the new policy will be implemented in ways that enable equitable outcomes for marginalized groups. Other regulatory science research has evaluated the effects of nicotine in cigarettes on a model of cigarette experimentation, the impact of flavors in cigarettes and e-cigarettes, and the influence of product characteristics and policy on multiple tobacco product use. He has led other groundbreaking research on the influence of drug-associated environments on drug use, relapse, and treatment; tobacco use disparities among individuals with comorbid psychiatric (e.g., ADHD, serious mental illness) and health (e.g., HIV; chronic pain) problems.
Dr. McClernon has actively mentored early career individuals from high school students through early career faculty. His former postdoctoral fellows are faculty or staff scientists at academic medical centers, government agencies, and research institutes. He has been continuously NIH-, FDA-, and foundation- funded since 2002. He has authored/co-authored more than 170 peer-reviewed publications, has two patents, has served as chair of NIH grant review panels, and is the recipient of numerous awards including the Society for Research on Nicotine and Tobacco Jarvik-Russell New Investigator Award. In 2024 he was recognized for excellence in mentoring when he was awarded the Career Mentoring Award in Clinical Research by the Duke University School of Medicine.
Allison Elizabeth Ashley-Koch
My work focuses on the dissection of human traits using multi-omic technologies (genetics, epigenetics, metabolomics and proteomics). I am investigating the basis of several neurological and psychiatric conditions such as neural tube defects and post-traumatic stress disorder. I also study modifiers of sickle cell disease.
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