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      Prediction of placebo responses: a systematic review of the literature

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          Abstract

          Objective: Predicting who responds to placebo treatment—and under which circumstances—has been a question of interest and investigation for generations. However, the literature is disparate and inconclusive. This review aims to identify publications that provide high quality data on the topic of placebo response (PR) prediction.

          Methods: To identify studies concerned with PR prediction, independent searches were performed in an expert database (for all symptom modalities) and in PubMed (for pain only). Articles were selected when (a) they assessed putative predictors prior to placebo treatment and (b) an adequate control group was included when the associations of predictors and PRs were analyzed.

          Results: Twenty studies were identified, most with pain as dependent variable. Most predictors of PRs were psychological constructs related to actions, expected outcomes and the emotional valence attached to these events (goal-seeking, self-efficacy/-esteem, locus of control, optimism). Other predictors involved behavioral control (desire for control, eating restraint), personality variables (fun seeking, sensation seeking, neuroticism), or biological markers (sex, a single nucleotide polymorphism related to dopamine metabolism). Finally, suggestibility and beliefs in expectation biases, body consciousness, and baseline symptom severity were found to be predictive.

          Conclusions: While results are heterogeneous, some congruence of predictors can be identified. PRs mainly appear to be moderated by expectations of how the symptom might change after treatment, or expectations of how symptom repetition can be coped with. It is suggested to include the listed constructs in future research. Furthermore, a closer look at variables moderating symptom change in control groups seems warranted.

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          Most cited references46

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          Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease.

          The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson's disease (PD). Little is known, however, about the mechanism underlying the placebo effect. Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography, we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo. Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system.
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            Individual differences in reward responding explain placebo-induced expectations and effects.

            Expectations, positive or negative, are modulating factors influencing behavior. They are also thought to underlie placebo effects, impacting perceptions and biological processes. Using healthy human subjects, we examined the role of the nucleus accumbens (NAC), a region centrally involved in the encoding of reward expectation, in the formation of placebo responses. Employing functional molecular imaging, activation of NAC dopamine (DA) release was observed during placebo administration and related to its anticipated effects, perception-anticipation mismatches, and placebo effect development. In additional functional MRI studies, the expectation of monetary gain increased NAC synaptic activity in a manner proportional to placebo-induced DA release, anticipated effects, perception-anticipation differentials, and actual placebo effects. Individual variations in NAC response to reward expectation accounted for 28% of the variance in the formation of placebo analgesia.
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              Placebo in emotional processing--induced expectations of anxiety relief activate a generalized modulatory network.

              Placebo analgesia and reward processing share several features. For instance, expectations have a strong influence on the subsequent emotional experience of both. Recent imaging data indicate similarities in the underlying neuronal network. We hypothesized that placebo analgesia is a special case of reward processing and that placebo treatment could modulate emotional perception in the same way as does pain perception. The behavioral part of this study indicates that placebo treatment has an effect on how subjects perceive unpleasant pictures. Furthermore, event-related fMRI demonstrated that the same modulatory network, including the rostral anterior cingulate cortex and the lateral orbitofrontal cortex, is involved in both emotional placebo and placebo analgesia. These effects were correlated with the reported placebo effect and were predicted by the amount of treatment expectation induced on a previous day. Thus, the placebo effect may be considered to be a general process of modulation induced by the subjects' expectations.
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                Author and article information

                Contributors
                Journal
                Front Psychol
                Front Psychol
                Front. Psychol.
                Frontiers in Psychology
                Frontiers Media S.A.
                1664-1078
                01 October 2014
                2014
                : 5
                : 1079
                Affiliations
                [1] 1Department of Internal Medicine – Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen Tübingen, Germany
                [2] 2Department of Psychology, Clemson University Clemson, SC, USA
                Author notes

                Edited by: Gian Mauro Manzoni, eCampus University, Italy

                Reviewed by: Eduardo Adrian Garza-Villarreal, Universidad Autónoma de Nuevo Leon, Mexico; Gabriele Roberto Cassullo, University of Turin, Italy

                *Correspondence: Bjoern Horing, Department of Psychology, Clemson University, 410J Brackett Hall, Clemson, SC 29634-1355, USA e-mail: bhoring@ 123456clemson.edu

                This article was submitted to Psychology for Clinical Settings, a section of the journal Frontiers in Psychology.

                Article
                10.3389/fpsyg.2014.01079
                4181242
                25324797
                e4a9af30-2bd5-45b7-aa98-32be895147ec
                Copyright © 2014 Horing, Weimer, Muth and Enck.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 July 2014
                : 08 September 2014
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 63, Pages: 10, Words: 8014
                Categories
                Psychology
                Review Article

                Clinical Psychology & Psychiatry
                placebo,placebo response prediction,pain,optimism,self-efficacy,personality

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