| Summary: | Impairments of social function are increasingly thought to be fundamental to the psychopathology of psychiatric disorders. Current treatments are not assessed against these social domains and the effects of medication are poorly understood. Furthermore, the neural mechanisms and psychopharmacology underlying these functions in the healthy population are poorly understood. This thesis addresses this knowledge gap. A meta-analysis of antipsychotic treatment effects on emotion processing in schizophrenia confirms the lack of efficacy of current treatments in treating these social deficits. Following this, the thesis largely focuses on social decision-making, investigating tasks which model trust, cooperation and social norm violations. A meta-analysis of neuroimaging studies investigating the Ultimatum Game (UG) provides robust evidence of regions underlying the processing of social norms. Results are presented from two psychopharmacological studies, utilising serotonergic agonists to investigate their effects on social decision-making and emotion processing. The first study administered psilocybin with an open-label design. This study additionally investigated the efficacy of a src-kinase inhibitor to attenuate any psilocybin effect; this followed a placebo-controlled, double-blind design. The second study investigated 3,4-methylenedioxymethamphetamine (MDMA) with a placebo-controlled, double-blind design. Both MDMA and psilocybin caused a decrease in rejection of unfair offers in the UG. MDMA increased cooperation with trustworthy, but not untrustworthy, partners in an iterated Prisoner’s Dilemma (PD), as well as reducing recognition of negative facial affect. Increased cooperation in the PD was accompanied by increased activation in the superior temporal sulcus, cingulate cortex and insula, during feedback of other player’s decisions. The findings of these studies suggest that serotonergic mechanisms are fundamental to the processing of normative behaviour during interpersonal interactions. Manipulation of this neurotransmitter system produced context-sensitive changes in behaviour. These behavioural alterations were accompanied by changes in activity of brain regions proposed to be involved in the processing and appraisal of other’s intentions and motivations. It is hypothesised that this was largely achieved through activity at the serotonin 2A receptor. These findings provide insight for the development of new treatment mechanisms for disorders of social cognition.
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