Decisions and inferences on internal, social and probabilistic information: insights from pharmacological challenge with citalopram and atomoxetine

Monoamines are essential neurotransmitters in the functioning of the central nervous system, and monoaminergic agents are widely used in clinical psychopharmacology. They have been linked by previous research to processes including decision making under uncertainty and in social environments, and affective inferences directed at the self and others, all of which show characteristic alterations in psychiatric conditions. However, important gaps remain in understanding the underlying neurocognitive mechanisms that elicit these effects, which if bridged may offer greater insight into the roles of monoamines in both the healthy human brain and in its dysfunction. This body of work investigates serotonergic links within three overlapping themes of inference on internal, probabilistic and social information, using a combination of pharmacological challenge, behavioural testing, magnetic resonance imaging and measures of cardiac activity. Citalopram, a selective serotonin reuptake inhibitor, was used to manipulate serotonin levels, while the noradrenergic reuptake inhibitor atomoxetine was used to alter levels of noradrenaline and prefrontal dopamine. Using healthy volunteers in double-blind placebo-controlled designs, we carried out a series of behavioural experiments with citalopram and atomoxetine, and neuroimaging experiments with citalopram. We determined that citalopram but not atomoxetine affected cardiac interoceptive awareness and decisions to sample information prior to making a choice. Pharmacological challenge on both drugs differentially affected paired social interactions depending on whether participants were in the same pharmacologically-induced state or not. We also showed changes in activation of brain regions implicated in interoceptive and emotional processing while carrying out related tasks, with some pharmacological effects, and which showed common areas between the two. This thesis therefore extends the understanding of monoaminergic contributions to essential inferential processes, as well as providing further evidence for shared neural substrates of emotion and interoception.