24 Jun Study Finds Link Between Genetic Variant, Opioid Addiction and Binge Eating
MedicalResearch.com Interview with:
Camron D. Bryant Ph.D
Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry
Boston University, Boston, MA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We previously used genome-wide linkage analysis, fine mapping, gene validation, and pharmacological targeting to identify a negative regulatory role for the gene casein kinase 1-epsilon (Csnk1e) in behavioral sensitivity to drugs of abuse, including psychostimulants and opioids.
Parallel human candidate genetic association studies identified an association between multiple genetic variants in CSNK1E with heroin addiction in multiple populations. Drug addiction is a multi-stage process that begins with the initial acute subjective and physiological responses that can progress to chronic administration, tolerance, and withdrawal. The recovery process begins with abstinence from drug taking but can quickly be derailed by relapse to drug taking behavior. Preclinical pharmacological studies also support a role for CSNK1E in reinstatement of opioid self-administration and relapse to alcohol drinking.
Despite the evidence that disruption of Csnk1e gene and protein function can affect various behaviors associated with drug and alcohol addiction, it is unclear what stage of the addiction process these genetic and pharmacological manipulations modulate. In this study, we show that disruption of the Csnk1e gene resulted in an enhancement of the rewarding properties of the highly potent and addictive opioid, fentanyl. Unexpectedly, we also discovered that disruption of Csnk1e also enhanced binge eating – but only in female mice.
MedicalResearch.com: What should clinicians and patients take away from your report?
- Our findings have clear implications for human genetic association studies of CSNK1Ewith heroin addiction where we predict that CSNK1Evariants will be associated with differential susceptibility to the pleasurable, euphoric effects of opioids which can influence risk for opioid abuse.
- The female-specific increase in binge eating following disruption of the Csnk1egene suggests that the genetic basis of binge eating and eating disorders will likely differ (at least partly) in females versus males. A second implication is that the future goal of precision medicine for treating binge eating may be tailored not only to one’s genotype but also to one’s sex.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: With regard to the opioid findings, in order to test our hypothesis in humans, healthy individuals with limited exposure to opioids could be tested for their subjective sensitivity to the pleasurable/euphoric effects of opioids in a controlled laboratory setting.
With regard to the female-specific increase in binge eating in mice with a Csnk1e mutation, an important limitation of this study is that we did not monitor the stage of the estrus cycle. Thus, future preclinical investigations should incorporate phase of estrus cycle into the experimental and statistical model which will address whether circulating sex hormones are a contributing factor to the genotype by sex interaction that we observed. Similarly, human genetic association studies of binge eating in humans should consider stage of menstrual cycle in assessing the history of binge eating episodes – this could improve the ability to detect genome-wide associations.
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Goldberg, L. R., Kirkpatrick, S. L., Yazdani, N., Luttik, K. P., Lacki, O. A., Babbs, R. K., Jenkins, D. F., Johnson, W. E. and Bryant, C. D. (), Casein kinase 1-epsilon deletion increases mu opioid receptor-dependent behaviors and binge eating. Genes, Brain and Behavior. Accepted Author Manuscript. doi:10.1111/gbb.12397
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