The relationship between serotonin, decision-making and mood

In: Doctoral thesis, UCL (University College London).

Abstract

The serotonin (5-HT) system has been implicated in both depression and reward and punishment processing. This thesis presents data from four studies designed to better understand the role of serotonin in decision-making and mood. Following the general introduction and description of the main experimental methods, the first experimental chapter presents a study that examined the relationship between naturally-varying 5-HT1A receptor availability, measured using positron emission tomography, and decision-making in healthy volunteers. This study identified correlations between 5-HT1A receptor availability in the hippocampal complex and both impulsivity and sensitivity to the probability of an outcome during decision-making. The second experimental chapter examined decision-making in healthy volunteers 3 days following MDMA (3,4-methylenedioxymethamphetamine) administration, when serotonin transmission is thought to be reduced. A specific type of decision-making process, "pruning" (the reflexive avoidance of aversive outcomes when searching through a tree of potential decisions), was significantly attenuated 3 days following MDMA administration. However, the expected positive relationship between the attenuation in this decision-making process and low mood was not observed. The third experimental chapter attempted to extend this finding using the acute tryptophan depletion method, which removes tryptophan (the precursor to serotonin) from the diet and is thought to reduce serotonin synthesis. Performance on three decision making tasks (pruning, gambling and impulsivity) was examined in healthy volunteers following tryptophan depletion. Results revealed that treatment decreased participants' choosing of high probability gambles. The final chapter examined pruning in unmedicated depressed patients, and found that they behaved very similarly to healthy volunteers when evaluating aversive outcomes in the context of a tree of potential decisions, despite the hypothesised disruption to the serotonin system in this disorder. These experiments provide a more complete understanding of the relationship between serotonin, decision-making and mood, and are discussed in relation to theories of depression that pose a central role for disrupted decision-making.