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Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

ABSTRACT: UNLABELLED: BACKGROUND:Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness. METHOD:Healthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. RESULTS:Response bias, the participants' propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the COMT genotype (Val/Val) associated with relatively increased phasic dopamine signaling and cognitive flexibility. CONCLUSIONS:The combination of success in promotion goal pursuit and Val/Val genotype appears to facilitate responding to reward opportunities in the environment. This study is among the first to integrate an assessment of self-regulatory style with an examination of genetic variability that underlies responsiveness to positive outcomes in goal pursuit.

SUBMITTER: Goetz EL

PROVIDER: S-EPMC3570330 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

Goetz Elena L EL Hariri Ahmad R AR Pizzagalli Diego A DA Strauman Timothy J TJ

Biology of mood & anxiety disorders 20130201 1

<h4>Unlabelled</h4><h4>Background</h4>Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue respon ...[more]

PMID: 23369671

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Project description:Reward-related disturbances after withdrawal from nicotine are hypothesized to contribute to relapse to tobacco smoking but mechanisms underlying and linking such processes remain largely unknown.To determine whether withdrawal from nicotine affects reward responsiveness (ie, the propensity to modulate behavior as a function of prior reinforcement experience) across species using translational behavioral assessments in humans and rats.Experimental studies used analogous reward responsiveness tasks in both humans and rats to examine whether reward responsiveness varied in (1) an ad libitum smoking condition compared with a 24-hour acute nicotine abstinence condition in 31 human smokers with (n?=?17) or without (n?=?14) a history of depression; (2) rats 24 hours after withdrawal from chronic nicotine (n?=?19) or saline (n?=?20); and (3) rats following acute nicotine exposure after withdrawal from either chronic nicotine or saline administration.Performance on a reward responsiveness task under nicotine and nonnicotine conditions.In both human smokers and nicotine-treated rats, reward responsiveness was significantly reduced after 24-hour withdrawal from nicotine (P?<?.05). In humans, withdrawal-induced deficits in reward responsiveness were greater in those with a history of depression. In rats previously exposed to chronic nicotine, acute nicotine reexposure long after withdrawal potentiated reward responsiveness (P?<?.05).These findings across species converge in suggesting that organisms have diminished ability to modulate behavior as a function of reward during withdrawal of nicotine. This blunting may contribute to relapse to tobacco smoking, particularly in depression-vulnerable individuals, to reinstate responsiveness to natural rewards and to experience potentiated nicotine-induced reward responsiveness. Moreover, demonstration of behavioral homology across humans and rodents provides a strong translational framework for the investigation and development of clinical treatments targeting reward responsiveness deficits during early withdrawal of nicotine.

Project description:Background: Mental healthcare needs person-tailored interventions. Experience Sampling Method (ESM) can provide daily life monitoring of personal experiences. This study aims to operationalize and test a measure of momentary reward-related Quality of Life (rQoL). Intuitively, quality of life improves by spending more time on rewarding experiences. ESM clinical interventions can use this information to coach patients to find a realistic, optimal balance of positive experiences (maximize reward) in daily life. rQoL combines the frequency of engaging in a relevant context (a 'behavior setting') with concurrent (positive) affect. High rQoL occurs when the most frequent behavior settings are combined with positive affect or infrequent behavior settings co-occur with low positive affect. Methods: Resampling procedures (Monte Carlo experiments) were applied to assess the reliability of rQoL using various behavior setting definitions under different sampling circumstances, for real or virtual subjects with low-, average- and high contextual variability. Furthermore, resampling was used to assess whether rQoL is a distinct concept from positive affect. Virtual ESM beep datasets were extracted from 1,058 valid ESM observations for virtual and real subjects. Results: Behavior settings defined by Who-What contextual information were most informative. Simulations of at least 100 ESM observations are needed for reliable assessment. Virtual ESM beep datasets of a real subject can be defined by Who-What-Where behavior setting combinations. Large sample sizes are necessary for reliable rQoL assessments, except for subjects with low contextual variability. rQoL is distinct from positive affect. Conclusion: rQoL is a feasible concept. Monte Carlo experiments should be used to assess the reliable implementation of an ESM statistic. Future research in ESM should asses the behavior of summary statistics under different sampling situations. This exploration is especially relevant in clinical implementation, where often only small datasets are available.

Dataset Information

Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

Publications

Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

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