Uncontrollable stress, dopamine and decision-making in health and depression: Preliminary study

PI: Marc Guitart-Masip

The diagnosis of depression encompasses a very diverse group of patients with different disease pathways and responses to available treatments. Despite this, we do not have any markers that helps clinicians predict clinical outcomes in individual patients. Decision-making is an interesting area that can potentially provide clues to improve our understanding of depression and its clinical management. To make decisions, the brain uses a variety of cognitive functions and in recent years the scientific understanding of these has increased considerably.

Depressed patients show different changes in their ability to make decisions, and this is likely related to changes in dopamine systems. Dopamine is a substance that supports the motivation of actions and is released in the brain as you learn which actions lead to rewards. Previous experiments with animal models have shown that uncontrollable stress causes changes in decision-making that are associated with changes in the dopamine system. Our hypothesis is that a subgroup of depressed patients who do not respond to the usual antidepressant treatments show changes in their decision making that are similar to those observed in animals subjected to uncontrollable stress. Despite this, it is currently unknown how uncontrollable stress affects the dopamine system and decision making in healthy or depressed people.

In this project, we will develop an experimental paradigm to test how healthy subjects respond in stressful situations when they have the opportunity to interrupt the stress (controllable stress) or are unable to interrupt it (uncontrollable stress). We will first characterize how controllable and uncontrollable stress affect healthy people’s ability to make decisions in different contexts, as well as how their brain works when making decisions. If we are successful in developing this new experimental paradigm, we will be able to use it in future studies to characterise the response of the dopaminergic system. Furthermore, this knowledge will be useful to develop behavioural markers for stress-induced changes, which can then be used to detect depressed patients with extreme changes in decision-making ability.

The project is funded by a grant from the Swedish Research Council (Vetenskapsrådet).