Dopamine manipulations modulate paranoid social inferences in healthy people

J M Barnby,M A Mehta,V Bell,Q Deeley

doi:10.1038/s41398-020-00912-4

Abstract

Altered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. Twenty seven healthy male participants received 150mg L-DOPA, 3 mg haloperidol, or placebo in a double-blind, randomised, placebo-controlled study, over three within-subject sessions. Participants completed a multi-round Dictator Game modified to measure social attributions, and a measure of belief salience spanning themes of politics, religion, science, morality, and the paranormal. We preregistered predictions that altering dopamine function would affect (i) attributions of harmful intent and (ii) salience of paranormal beliefs. As predicted, haloperidol reduced attributions of harmful intent across all conditions compared to placebo. L-DOPA reduced attributions of harmful intent in fair conditions compared to placebo. Unexpectedly, haloperidol increased attributions of self-interest about opponents’ decisions. There was no change in belief salience within any theme. These results could not be explained by scepticism or subjective mood. Our findings demonstrate the selective involvement of dopamine in social inferences related to paranoia in healthy individuals.

Highlights

IntroductionEpidemiological evidence suggests that paranoia exists on a spectrum in the general population, ranging from mild social concerns to persecutory delusions[2,3]
Paranoia involves unfounded beliefs that others intend harm[1]
One participant was removed from the analysis for having a very high Green et al Paranoid Thoughts Scale (GPTS; ref. 36) score (104) over two standard deviations away from the mean of the rest of the sample (46.52), potentially making our analysis less conservative

Summary

Introduction

Epidemiological evidence suggests that paranoia exists on a spectrum in the general population, ranging from mild social concerns to persecutory delusions[2,3]. Observational and experimental research has identified a range of personal and interpersonal factors that influence paranoia. Worry[4], insomnia[5], belief inflexibility[6], and safety behaviours[7] all contribute to the formation and/or maintenance of paranoia. Antipsychotic medication primarily has its effect through antagonism at D2 dopamine receptors in the mesolimbic and nigrostriatal pathway[18]. Stimulant drugs, which increase activity at mesolimbic D2 dopamine receptors, raise the risk of psychosis—with over 40% of recreational methamphetamine users developing psychosis[19] of which paranoid delusions are the dominant symptom[20]

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Discussion

Conclusion