Decision-making problems in psychotic disorders with Dr James Kesby

Tell us about your research area. 

We use a translational approach, incorporating preclinical approaches and clinical testing to ascertain what decision-making phenotype are observed in those with psychosis and their potential mechanisms.

Dr James Kesby

Advanced Researcher and Senior Lecturer, Queensland Centre for Mental Health Research/Queensland Brain Institute

Researcher profile

What was the purpose of your research? 

To better understand the progression and nature of problems in how people respond to rewards and losses in complex environments. This may allow us to better identify what intervention/treatment approaches are going to be beneficial for an individual with psychosis. Moreover, it will provide the foundation for developing new interventions and treatments.

How was your research conducted? 

We recruited people with and without psychosis at multiple illness stages (early and persistent psychosis). We used a combination of cognitive tests (outcome-specific devaluation and reversal learning) to assess goal-directed behaviour and cognitive flexibility (how we respond to environmental changes). These tests are conducted on a computer with a joystick box. The participant completes multiple trials and stages to learn action-outcome and stimulus-outcome associations.

Why was the research conducted in this manner?

These specific tasks are known to require corticostriatal circuitry implicated in the neurobiology of psychotic disorders. We hypothesised that if core regions (namely the associative striatum) were not functioning properly, we would see deficits in both tasks. 

What were the outcomes of the research?

A large proportion of those with persistent psychosis showed impairments in goal-directed behaviour (whereas very few control subjects or people with early psychosis showed impairments). It was this same group of individuals with persistent psychosis who showed the greatest impairments in cognitive flexibility. Their behavioural phenotype supported prior literature looking at cognitive flexibility, but we showed that this was driven largely by a distinct subgroup of those with persistent psychosis. We also used computational modelling to demonstrate that these differences in performance were due to sluggish experience updating and less deterministic choices rather than an overall decrease in performance. 

Were there any unexpected findings?

We had expected to see more obvious impairments in those treated with clozapine, compared with those on standard antipsychotics. Although a greater proportion of impairment was observed, this was only a modest increase.

What does this research mean for the people of Queensland? 

Ideally, this will allow us to develop cognitive assessments that can identify people with psychosis who may face larger problems with decision-making. We can then provide further support to help these people manage these problems and live to their full potential. In the longer term, this work will allow for more targeted approaches to prevent or decrease the decline in functioning.

Does this open the door to any further research topics?

Yes, we are very interested in exploring the specific aspects of this cognitive phenotype so that we can identify the most sensitive measure for prognostic prediction. Furthermore, preclinical studies can help to understand what neural circuits may underlie these problems.

Do you have any advice for aspiring mental health researchers?

Mental health research is so important for the well-being of many people. We need to continue to learn more about the brain (in general) and how dysfunction can lead to behavioural and neurological problems if we are to improve clinical outcomes in this space. Although it can be challenging at times, it is also a very rewarding field. Their are also many great researchers who are happy to provide feedback and help for someones research journey. 

Are there any other related studies you’d recommend people to read?

We have also published these behavioural outcomes in those early psychosis: Reversal learning in those with early psychosis features contingency-dependent changes in loss response and learning.

Our preclinical studies have also begun to show what areas of the brain may underlie problems in goal-directed behaviour (Activating the dorsomedial and ventral midbrain projections to the striatum differentially impairs goal-directed action in male mice) and cognitive flexibility (Activity in the Dorsomedial Striatum Underlies Serial Reversal Learning Performance Under Probabilistic Uncertainty).