The neurocognitive mechanisms of paranoia

Paranoia is the unwarranted belief that others intend harm, either now or in the future. It is one of the most predictive factors for transition into psychosis, as well as being the most common content of delusional beliefs, known as persecutory delusions. A prominent theory of psychosis suggests that dopaminergic dysregulation in midbrain regions lead to the production of positive symptoms, such as persecutory delusions, and indeed observational evidence demonstrates that blocking post-synaptic dopamine through the administration of antipsychotics can reduce some of these symptoms. However, most mechanistic evidence that aim to test explanatory frameworks of persecutory delusions has focused on the role of dopamine in non-social learning, general cognition and perception. Focusing on non-social mechanisms strongly neglects the clearly social content of persecutory delusions, and therefore the role dopamine may play in the formation of paranoid beliefs. Further still, the well evidenced role of social attributions in paranoia and persecutory delusions has not been fully explained with reference to potential neurocognitive mechanisms that may underlie them. This thesis aims to fill this knowledge gap by developing an experimental test of social attributions in paranoia, developing a computational model that may explain their development and maintenance, and using a psychopharmacological double-blind placebo cross over study to test the role of dopaminergic mechanisms in their generation. I first demonstrate the psychometric properties of the Beliefs and Values Inventory - a novel measure to assess five themes of belief down three dimensions -in a large online population (n = 1763). Secondly, I utilise large online populations (n = 1754) to test how pre-existing paranoid beliefs may influence in-the-moment attributions of harmful intent during a social task using real human decisions, a modified serial Dictator game. The Dictator game suggested that paranoid beliefs lead to faster and larger harmful intent attributions, but not attributions of self-interest. By applying a computational model to the serial Dictator game data, I also found that pre-existing paranoid beliefs and those most likely to attribute high harmful intent are more uncertain about their partner's policy and are more sensitive to the social environment. Finally, I ran a double-blind, within subjects, randomised-control trial using LDOPA and haloperidol to moderate presynaptic and postsynaptic dopamine, respectively, in 30 healthy participants. Following dosing, participants were asked to fill in the Beliefs and Values Inventory and play the within-subjects dictator game. Results suggested that haloperidol selectively reduced harmful intent attributions and increased self-interest attributions across the board, however, did not affect any other themes of beliefs. We conclude that dopamine is crucial in processing the self-relevance of social intent from others. In sum, this thesis demonstrates that paranoid beliefs i) are along an exponential spectrum in the general populations, ii) influence the live attribution of harmful intent toward ambiguous social actions, iii) increase the probability that in-the-moment harmful intent attributions will be made, iv) increase the uncertainty about another's policy, and v) dopamine is crucial to in-the-moment paranoia. I suggest these results converge and integrate with evidence from adjacent fields of social learning to update current models of paranoia.