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Fear reduction strategies relevant for exposure therapy: Devaluation and extinction learning in anxiety disorder patients and their neurobiological basis

Periodic Reporting for period 1 - ReduceFear (Fear reduction strategies relevant for exposure therapy: Devaluation and extinction learning in anxiety disorder patients and their neurobiological basis)

Berichtszeitraum: 2019-10-01 bis 2021-09-30

The aim of ReduceFear is to examine fear reduction strategies that play a role in exposure therapy, the gold standard therapy for anxiety disorders and PTSD. These disorders are highly common, and up to 50% of patients do not benefit from the therapy. The project will concurrently assess (a) extinction learning, a process that reduces the over-expectation of harm but is highly fragile and dysfunctional in anxiety patients, and (b) threat (US) devaluation, a highly-understudied process that has potential to more robustly reduce excessive fears by reducing the perceived aversiveness of the threat. Overall objective: to examine for the first time (1) the neurobiological mechanisms of US devaluation compared to extinction learning to identify (pre)clinical targets for therapy augmentation, and (2) US devaluation mechanisms in patients with anxiety disorders. If anxiety patients not show any deficits in US devaluation, exposure-based therapies may be adapted to enhance focus on US devaluation.
My first objective was to validate a task to directly compare US devaluation and extinction learning and my second objective was to compare neural mechanisms of US devaluation relative to extinction learning. My third objective was to validate a US devaluation and extinction learning task for clinical settings, and my fourth objective to assess US devaluation and extinction learning in anxiety disorder patients.
During the project I have been mainly working on setting up and running studies a part of the proposed studies, as well as analyses and writing. In addition, I have focused on the development of core research skills, such as project management, longitudinal data modelling, and teaching. Outside of the project, I have been working as a clinical psychologist (50%).

Overview of the results, incuding exploitation/dissemination:
I have published a paper that describes two modern research frameworks in psychopathology and mental health: Experimental Psychopathology and the Research Domain Criteria. These frameworks have been developed in order to increase our understanding of the development, maintenance and treatment of mental health. Central to both of them is the inclusion of experimental methods. This paper describes overlaps and differences between these research frameworks, as well as their individual pitfalls and strengths. It also provides ideas what ways these frameworks could benefit in order to further help mental health research.For this publication, we did an extensive literature search and had multiple discussions about the topic. When the paper was published, the paper has been sent around to our network. In addition, I have been invited to present the paper at the EPP meeting; a large Dutch/Belgian meeting where typically all researchers in experimental psychopathology meet. My colleague S. Papalini has presented this paper, as I have been on maternity leave.

I have contributed to a paper published in Nature reviews psychology, for which I conducted a literature search and wrote a large section. This paper described how Pavlovian fear conditioning has been the prime research instrument that has led to substantial progress in understanding the multi-faceted psychological and neurobiological mechanisms of fear in past decades. In this Perspective, we suggest that use of Pavlovian fear conditioning as a laboratory model of clinical anxiety requires moving beyond the study of fear acquisition to associated fear conditioning phenomena: fear extinction, generalization of conditioned fear and fearful avoidance. Understanding individual differences in each of these phenomena, not only in isolation but also in how they interact, will further strengthen the external validity of the fear conditioning model as a tool with which to study maladaptive fear as it manifests in clinical anxiety.

I have ran a laboratory study (objective 1) on the effects of US devaluation compared to extinction learning, that measured both self-report as well as psychophysiology (skin conductance responses). This study shows that both US devaluation and extinction learning are effective strategies to reduce fear and that they have comparable effects on contextual renewal. The results were presented at the European meeting of Human Fear Conditioning (EMHFC), which is a conference for research both within and outside the EU that are working in my specific field. I am currently writing up the paper, which I aim to publish within the next six months.

I have also conducted an online study (objective 3) to develop a task that can be used in any mental health clinical assessing US devaluation and extinction learning. This study has showed comparable results to the laboratory study. Yet, US devaluation seemed to be slightly less effective in reducing fears compared to extinction learning. For objective 4, I have reached out to several mental health institutions to have them on board to contribute in a patient study, but because of critical risks and delays (covid-19) I have been chosen to work with plan B (mitigation plan): I have run a second large online study in the KU Leuven student population, that included several markers of anxiety psychopathology as well as avoidance behaviors. These results are currently analyzed. I am also planning to publish these data, probably combined within one paper.

The neuroimaging study (objective 2) was unfortunately not executed during the grant period due to several circumstances.
With respect to the project data: The data of the project so far show that US devaluation, compared to extinction learning, has no additional value with respect to reducing fear responses during contexrual renewal. In other words, both fear reduction strategies seem to be equally effective in dimimnishing fear responses across different contexts. Although the results with respect to high anxious individuals should still be analyzed, the data imply that both strategies could have an equivalent role in exposure therapy for excessive anxiety. Based on the study, clinicians can be made more aware that different fear reduction strategies have distinct underlying mechanisms. Potentially, by using these strategies complementary during exposure therapy for anxiety disorders, therapy might be made more effective.

With respect to the other two publications: the wider potential impact is that these papers contribute to a larger number of opinion papers helping other researchers to be more aware of the strengths/pitfalls of the methods they are using and to stay critical about how to improve research designs. That may help the field of mental health research in the long run. The impact of an individual paper on a socio-economic or societal level is however difficult to estimate.
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