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STOP-JIA

More on the Mind

By: Ken Schikler, MD | April 20, 2016 | What Caught Our Eye

After Rob Fuhlbrigge’s previous entry regarding the “power of the mind” and physiologic symptoms, I thought it timely to bring up a somewhat related paper. As CARRA members, we are involved in clinical trials that assess the safety and efficacy of an “active intervention” as compared to a “sham” or Placebo intervention. In “Genetics and the placebo effect: the placebome” (Molecular Medicine, May 2015, vol 21, no 5, 285-294), Hall, Loscalzo and Kaptchuk have reviewed what is known about genetics and the placebo effect with specific reference to pain reduction. This would have clear implications for those trials that include pain as an outcome measure in trials for the treatment of inflammatory diseases, as well as those conditions that are considered “non-inflammatory.”

Recent innovative neuroimaging and physiologic experiments have fostered the current viewpoint that placebo effects are biologic responses to psychosocial stimuli and cues surrounding the administration of inactive (or active) treatments. Enhanced placebo responders in the “active treatment” arm of a trial would skew results. The ability to identify subjects prior to entry into clinical trials as placebo-prone individuals  would allow for balanced assignments into all arms of trials  so that a more refined data analysis might be made.

The authors additionally point out that identification of an enhanced placebo responder group might provide for dosing variation for those individuals who would be gaining benefit from a drug-plus-placebo effect as opposed to patients who might require higher dosing to obtain the desired outcome. Polymorphisms in candidate genes that may be the components of the “Placebome” are identified. The genes identified are those responsible for  signaling  variations in dopamine, serotonin, opioid and endocannabinoid effects. The authors have discussed the practical and ethical implications of how an identified “Placebome” could be applied to both randomized clinical trials in addition to clinical care and personalized medicine.

For those within CARRA with an interest in fibromyalgia, Ablin and Buskila give us “Update on the genetics of the fibromyalgia syndrome” (Best Practice & Research Clinical Rheumatology, 29 (2015)20-28). We find some overlap in candidate genes for this disorder and the “Placebome”, COMT, and Dopamine Receptor III, 5-Hydroxytryptamine receptor 2A.

While our genetic construct is being better understood, concomitant knowledge of epigenetics, for example, the effects of early childhood toxic stress on gene expression and the evolution of disease states must be explored.  

The more that research teaches us, the more I am reminded how much more there is to learn. Our biology responds to each and everything that occurs in our environment.