Universiteit Leiden

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Research project

Replacing fear with something new: Using novelty to unlearn fear.

This project has two main aims: I. Determine when novelty promotes fear extinction. II. Discover the neurobiological mechanisms underlying these effects.

Contact
Judith Schomaker
Funding
LUF Gratama Stichting

Anxiety disorders are the most frequent mental illness (~14% of the general population)1. A sedentary lifestyle further increases anxiety levels, and prevalence of anxiety disorders is even higher in elderly2. In our aging population, that has become increasingly sedentary (even more so during COVID-19 times), it is expected that the prevalence of anxiety disorders will increase steeply in the coming decades3,4. Alarmingly, as the above number already suggests, treatments that have a prolonged effect on anxiety relief are lacking, and relapse often occurs after treatments are finished5. Therefore, novel treatments to treat anxiety more effectively hold significant clinical value.

 

Scientific relevance:

The central mechanism underlying anxiety disorders is believed to be related to how we learn new associations and can be explained by classical conditioning. Although learned associations help us identify contexts in which we can find reward or expect punishment, sometimes they can be maladaptive. In fear conditioning a neutral stimulus becomes associated with an aversive outcome through repeated pairing6. This process has long been considered the central mechanism underlying anxiety disorders. For example, models of learning suggest that symptoms of post-traumatic stress disorder (PTSD), such as extreme fear and anxiety, are developed through conditioning mechanisms. Normally the fearful response becomes weaker and disappears after the threatening stimulus is no longer presented together with the trigger. This process is called extinction. In patients with anxiety disorders, this process is deficient, such that fearful responses are retained longer than in healthy individuals9. Patients with PTSD, for example, often experience debilitating anxiety in response to everyday events.

 

Aims for current research:

Previous studies have found positive effects of novelty on learning, with memory enhancements after people explore a novel environment10,11,12. One study suggested that novelty can also promote fear extinction: When a novel, non-threatening stimulus was presented during extinction, fearful responses were diminished faster, in both rats and humans5,13. Thus, novelty could be used to override associative learning that has become maladaptive, but clinical applications do not yet exist14. The current project aims to determine when and how novelty promotes fear extinction and paves the way to the development of interventions in which novelty is employed to unlearn fear in patients with anxiety disorders.

1. Wittchen, H. U., Jacobi, F., Rehm, J., Gustavsson, A., Svensson, M., J├Ânsson, B., & Steinhausen, H. C. (2011). The size and burden of mental disorders and other disorders of the brain in Europe 2010. European neuropsychopharmacology, 21(9), 655-679.

2. Edwards, M. K., & Loprinzi, P. D. (2016). Experimentally increasing sedentary behavior results in increased anxiety in an active young adult population. Journal of affective disorders, 204, 166-173.

3. Tremblay, M. S., Colley, R. C., Saunders, T. J., Healy, G. N., & Owen, N. (2010). Physiological and health implications of a sedentary lifestyle. Applied physiology, nutrition, and metabolism, 35(6), 725-740.

4. Meyer, J., McDowell, C., Lansing, J., Brower, C., Smith, L., Tully, M., & Herring, M. (2020). Changes in physical activity and sedentary behavior in response to COVID-19 and their associations with mental health in 3052 US adults. International journal of environmental research and public health, 17(18).

5. Dunsmoor, J. E., Campese, V. D., Ceceli, A. O., LeDoux, J. E., & Phelps, E. A. (2015). Novelty-facilitated extinction: providing a novel outcome in place of an expected threat diminishes recovery of defensive responses. Biological psychiatry, 78(3), 203-209.

6. Lissek, S., Powers, A. S., McClure, E. B., Phelps, E. A., Woldehawariat, G., Grillon, C., & Pine, D. S. (2005). Classical fear conditioning in the anxiety disorders: a meta-analysis. Behaviour research and therapy, 43(11), 1391-1424.

7. Pavlov, I. P. (1897/1902). The work of the digestive glands. London: Griffin.

8. Pavlov, I. P. (1927). Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex. Translated and edited by Anrep, GV (Oxford University Press, London, 1927).

9. Milad, M. R., Orr, S. P., Lasko, N. B., Chang, Y., Rauch, S. L., & Pitman, R. K. (2008). Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. Journal of psychiatric research, 42(7), 515-520.

10. Schomaker, J. (2019). Unexplored territory: beneficial effects of novelty on memory. Neurobiology of learning and memory, 161, 46-50.

11. Schomaker, J., & Meeter, M. (2015). Short-and long-lasting consequences of novelty, deviance and surprise on brain and cognition. Neuroscience & Biobehavioral Reviews, 55, 268-279.

12. Schomaker, J., van Bronkhorst, M. L., & Meeter, M. (2014). Exploring a novel environment improves motivation and promotes recall of words. Frontiers in psychology, 5, 918.

13. Lucas, K., Luck, C. C., & Lipp, O. V. (2018). Novelty-facilitated extinction and the reinstatement of conditional human fear. Behaviour research and therapy, 109, 68-74.

14. Cukor, J., Spitalnick, J., Difede, J., Rizzo, A., & Rothbaum, B. O. (2009). Emerging treatments for PTSD. Clinical psychology review, 29(8), 715-726.

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