Neural mechanisms of cognitive bias and its role in the triggering of the stress response in zebrafish

Project Information

BIASTRESS

Grant agreement ID: 703285

DOI

10.3030/703285

Project closed

EC signature date 14 March 2016

Start date 1 May 2016

End date 30 April 2018

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 160 635,60

EU contribution

€ 160 635,60

Coordinated by

FUNDACAO CALOUSTE GULBENKIAN
Portugal

Periodic Reporting for period 1 - BIASTRESS (Neural mechanisms of cognitive bias and its role in the triggering of the stress response in zebrafish)

Reporting period: 2016-05-01 to 2018-04-30

Summary of the context and overall objectives of the project

Stress has long been a major concern among researchers interested in health and welfare. Most of their work has considered stress from either a biological or an environmental perspective, focusing on the activation of the physiological systems involved in the stress process or the role of stressful life events in specific diseases. While interesting, if we are to fully understand the effects of stress on health, we must also take into account a psychological perspective that considers an individual’s perception (i.e. subjective) of stress. In this way, the involvement of appraisal in the activation of the stress response opens up the potential for evaluation biases (i.e. some individuals will consistently evaluate ambiguous stimuli as negative - pessimistic, and others as positive - optimistic). This is a relevant aspect, since assessing the stress resilience of optimistic and pessimistic phenotypes may be crucial for the study of stress-related disorders (SRD) (e.g. anxiety and depression), which will be extremely useful for developing ways to mitigate the effects of chronic stress. Moreover, this project has the potential to also be helpful in the field of antidepressant drug research, since pessimistic and optimistic individuals may diverge in their response to antidepressants. In this scenario, the overall aim of this project is to unravel the neural mechanisms of cognitive bias and its role in the triggering of the stress response as well as whether these personality traits are meaningfully linked to resilience to SRD, using zebrafish (Danio rerio) as a model. In line with the ongoing development of scientific knowledge and methodologies, zebrafish has become increasingly valuable as a translational research model, and is now contributing to hundreds of studies on human disease mechanisms worldwide, ranging from neurological and psychiatric disorders to stress-associated diseases. The specific objectives that were designed to achieve the project goal are:

Objective 1: To develop a behavioural assay for testing cognitive bias in zebrafish, and to characterise the behavioural and neuroendocrine profiles of “optimistic” versus “pessimistic” individuals.

Objective 2: To assess whether cognitive bias (i.e. pessimistic bias) is mediating inter-individual variations in susceptibility to the detrimental effects of stress.

Objective 3: To use the available GAL4-UAS enhancer trapped lines in zebrafish to study the loss of function (i.e. genetic inactivation) of specific neural circuits involved in the cognitive appraisal of stressors.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the course of BIASTRESS, a cognitive bias test for zebrafish has been developed permitting individuals of this species to be phenotyped in an optimistic/pessimistic dimension. Results show that inter-individual variations in judgment bias are characterized by specific behavioural and neuroendocrine profiles, suggesting that they may be related to differences in coping styles. Results also show that optimistic and pessimistic individuals have different expression levels of stress-related genes in the brain, suggesting that cognitive bias towards optimistic/pessimistic judgments would have an impact on the activation of the stress axis. On the other hand, our results show, for the first time in a vertebrate model, that cognitive bias towards pessimistic judgments makes individuals more susceptible to the detrimental effects of chronic stress. In this scenario, inter-individual differences in cognitive bias seem to be linked to inter-individual variations in stress responses, thus revealing the potential for evaluating biases of stress that affect the individual’s vulnerability to stress-related diseases, with pessimistic individuals being more susceptible than optimistic ones.

Although results reported here have not been yet submitted or published elsewhere, it is expected that 3 articles will be published in the near future. Moreover, particular importance has been given to the early communication of the results at international scientific conferences. On the other hand, aware of the real importance of promoting communication between the scientific community and the general public, several outreach activities have been carried during the course of BIASTRESS. A personal website was created with the aim to publicise any important findings of this project (https://oliveiralab.org/people/felipe-espigares/). Furthermore, the researcher is co-founder and member of SCIENFISH, a Facebook account created to publicise any important findings on fish research, including BIASTRESS results. Finally, BIASTRESS was present in the Institutional Open Day in 2017, in which IGC (Instituto Gulbenkian de Ciência) opened its doors to the community. The host lab presented some of ongoing research through several hands-on experiments, in which one of them was based on the cognitive bias paradigm.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Results show that optimistic and pessimistic individuals have different expression levels of stress-related genes in the brain, which suggest that cognitive bias towards optimistic/pessimistic judgments would have an impact on the stress response. In fact, optimistic and pessimistic individuals show a differential activation of the stress axis under chronic stress conditions. These results suggest that activation of the stress response depends not only on the intrinsic characteristics of the stressor, but also on the cognitive appraisal made by each individual of stressful events, with optimistic and pessimistic individuals having a different response threshold, and therefore differentially activating a stress response. Therefore, screening animals for pessimistic and optimistic phenotypes could be helpful in the field of antidepressant drug research, since pessimistic and optimistic animals may diverge in their response to antidepressants. Furthermore, our results also show, for the first time in a vertebrate model, that cognitive bias towards pessimistic judgments makes individuals more susceptible to the detrimental effects of chronic stress, since telomere attrition is associated with pessimistic individuals under chronic stress. In this scenario, inter-individual differences in cognitive bias seem to be linked to inter-individual variations in stress responses, thus revealing the potential for evaluating biases of stress that affect the individual’s vulnerability to stress-related diseases, with pessimistic individuals being more susceptible than optimistic ones. These findings would not therefore only be important for academia, but also ultimately for clinical practice, and may reinforce therefore the already strong European competitiveness in the area of stress-related health and management.