Moderators of the relationship between fear extinction learning and posttraumatic stress disorder

Zuj, DV ORCID: 0000-0002-6376-8354 2017 , 'Moderators of the relationship between fear extinction learning and posttraumatic stress disorder', PhD thesis, University of Tasmania.

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Abstract

$$Background:$$ Posttraumatic stress disorder (PTSD) is a psychiatric condition that occurs following a severe traumatic event, and is associated with distressing intrusive memories, avoidance of trauma reminders, hyperarousal, and negative (alterations in) cognitions and mood. A key theoretical model posits that symptoms persist, in part, due to impaired extinction of conditioned fear. Recent evidence suggests that the fear extinction account of PTSD is a complex multifaceted framework of important biological and cognitive features, including sleep quality, catastrophic negative appraisals, noradrenaline activity, and cortisol output. Little research, however, has examined these factors in relation to fear extinction in a PTSD population. Thus, the overall aim of the current thesis was to investigate factors that may moderate the relationship between fear extinction learning and PTSD symptom severity, thereby providing a greater understanding of the variables that shape the role of fear extinction learning in PTSD.
$$Method:$$ The current thesis includes a narrative review of relevant literature and four empirical studies, each assessing the moderating role of different key variables: (1) hours-since-waking (as a proxy for homeostatic sleep pressure); (2) catastrophic negative appraisals; (3) noradrenaline activity; and (4) cortisol output. These empirical studies used a cross-sectional sample of participants with PTSD, compared to trauma-exposed and non-exposed controls. Participants completed a standardized fear conditioning and extinction paradigm, providing skin conductance response as the primary index of conditioned responding. The PTSD Checklist was used as a diagnostic instrument to ascertain PTSD status and also provided an ordinal measure of PTSD symptom severity.
$$Results:$$ PTSD was associated with a number of fear extinction learning impairments, including altered responding to the CS+/- during the late extinction phase, and slower extinction learning during the early extinction phase, compared to trauma-exposed and non-exposed controls. Moderation analyses revealed that hours-since-waking and cortisol reactivity were significant moderators between fear extinction learning and PTSD symptom severity. Additionally, catastrophic negative appraisals and fear extinction learning were both associated with PTSD symptom severity, however there was no moderation interaction. Endogenous noradrenaline activity did not moderate the relationship between fear extinction and PTSD symptoms.
$$Conclusions:$$ The findings presented in the current thesis have a number of implications for the theoretical account of impaired fear extinction learning in PTSD, and for the implementation of exposure-based therapies for PTSD. In particular, we suggest that exposure therapies may be more beneficial if scheduled earlier in the day, rather than later; and recent findings that elevating cortisol leads to greater exposure therapy response in PTSD may be successful via enhancing fear extinction to safety signals. Finally, the results of the current thesis also suggest important biological and cognitive elements in PTSD symptoms, which may benefit from targeted treatment strategies.

Item Type: Thesis - PhD Zuj, DV posttraumatic stress disorder; fear extinction; psychophysiology; sleep; stress; trauma; risk factors; biomarkers; Copyright 2016 the author Chapter 2 appears to be the equivalent of a post-print version of an article published as: Zuj, D. V., Palmer, M. A., Lommen, M. J. J., Felmingham, K. L., 2016. The centrality of fear extinction in linking risk factors to PTSD: A narrative review, Neuroscience and biobehavioral reviews, 69, 15-35Chapter 3 appears to be the equivalent of the peer reviewed version of the following article: Zuj, D. V., Palmer, M. A., Hsu, C. K., Nicholson, E. L., Cushing, P. J., Gray, K. E., Felmingham, K. L., 2016. Impaired fear extinction associated with PTSD increases with hours-since-waking. Depression and anxiety, 33(3), 203-210, which has been published in final form at [http://dx.doi.org/10.1002/da.22463. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Chapter 4 appears to be the equivalent of a pre-print version of an article published as: Zuj, D. V., Palmer, M. A., Gray, K. E., Hsu, C. K., Nicholson, E. L., Malhi, G. S., Bryant, R. A., Felmingham, K. L., 2017. Negative appraisals and fear extinction are independently related to PTSD symptoms, Journal of affective disorders, 217, 246-251Chapter 6 appears to be the equivalent of a post-print version of an article published as: Zuj, D. V., Palmer, M. A., Malhi, G. S., Bryant, R. A., Felmingham, K. L., 2017. Endogenous cortisol reactivity moderates the relationship between fear inhibition to safety signals and posttraumatic stress disorder symptoms, Psychoneuroendocrinology, 78, 14-21. View statistics for this item