Glucocorticoids enhance extinction-based psychotherapy.

Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. Cortisol (20 mg) or placebo was administered orally 1 h before each of the treatment sessions. Subjects returned for a posttreatment assessment 3-5 d after the last treatment session and for a follow-up assessment after 1 mo. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights as measured with the acrophobia questionnaire (AQ) both at posttreatment and at follow-up, compared with placebo. Furthermore, subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up. The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy.

Impact of the COVID-19 pandemic on obsessive-compulsive symptoms in the Swiss general population.

Background: In the early stages of the COVID-19 pandemic, mental-health experts called attention to a possible deterioration of obsessive-compulsive symptoms (OCSs). In particular, people suffering from a fear of contamination were considered a vulnerable population. Aim: The aim of this study was to investigate the change in OCSs from before to during the pandemic within the Swiss general population, and to examine a possible relationship of OCSs to stress and anxiety. Methods: This cross-sectional study was implemented as an anonymized online survey (N = 3,486). The Obsessive-Compulsive Inventory-Revised (OCI-R) was used to assess global OCS severity (range: 0-72, clinical cut-off > 18) and specific OCS dimensions (range: 0-12) during the second wave of the pandemic and retrospectively for before the pandemic. Participants were asked to report stress and anxiety in the previous 2 weeks before the survey. Results: Participants reported significantly higher OCI-R total scores during (12.73) compared to before the pandemic (9.04, mean delta increase: 3.69). Significantly more individuals reported an OCI-R total score exceeding the clinical cut-off during (24%) than before the pandemic (13%). OCS severity increased on all symptom dimensions, but was most pronounced on the washing dimension (all with p < 0.001). Self-reported stress and anxiety were weakly associated with differences in severity in total score and symptom dimensions (with R2 < 0.1 and p < 0.001). Conclusion: Our results indicate that the full spectrum of people with OCS should be considered as risk groups for symptom deterioration during a pandemic and when assessing its possible long-term effects of such.

The Iranian Corona Stress Study: Psychological Impacts of COVID-19 Pandemic in an Iranian Population.

Background: To assess the psychological consequences of changes during the coronavirus 2019 (COVID-19) pandemic in the Iranian population. Methods: We performed an anonymous online survey in the first 3 weeks of March 2020. Individuals older than 14 who could read Persian, and lived in Iran, were eligible for the study. The participants had to rate their stress levels and depressive symptoms (using a nine-item Patient Health Questionnaire PHQ-9) during the last 2 weeks and before the pandemic retrospectively. The changes in the psychological measurements and their association with the sociodemographic factors and burdens due to confinement were assessed. Results: Overall, among the 3,210 subjects who participated in our study, both the stress levels and average depression scores increased. However, about 23% of the subjects reported a decrease in their stress levels. The burden of childcare, restrictions in private life, and thoughts about the future were positively correlated with the changes in the stress levels and depression scores (|r| > 0.15). However, feeling relieved in the pandemic condition, and enjoying more family time were associated with less change in the stress and depression scores. Being religious (odds ratio [OR] [CI]: 1.5 [1.3-1-8]) and older age (OR [CI]: 2.9 [1.8-4.6] for >55 years old) were identified as the resilience factors, whereas being a student (OR [CI]: 2.1 [1.6;2.7]), seeking a job (OR [CI]: 2.6 [1.8;3.9]), and history of a psychiatric disorder (OR [CI]: 3.2 [2.6;4]) were identified as the risk factors for depression. Conclusions: The stress levels and depressive symptoms have increased during the COVID-19 pandemic and this increase is related to different social and personal burdens due to the confinement conditions.

Effectiveness of a stand-alone, smartphone-based virtual reality exposure app to reduce fear of heights in real-life: a randomized trial.

Smartphone-based virtual reality (VR) applications (apps) might help to counter low utilization rates of available treatments for fear of heights. Demonstration of effectiveness in real-life situations of such apps is crucial, but lacking so far. Objective of this study was to develop a stand-alone, smartphone-based VR exposure app-Easy Heights-and to test its effectiveness in a real-life situation. We performed a single-blind, parallel group, randomized controlled trial. We recruited 70 participants with fear of heights, aged 18-60 years. Primary outcome was performance in a real-life Behavioral Avoidance Test (BAT) on a lookout tower after a single 1-h app use (phase 1) and after additional repeated (6 × 30 min) app use at home (phase 2). After phase 2, but not phase 1, participants in the Easy Heights condition showed significantly higher BAT scores compared to participants in the control condition (Cohen's d = 1.3, p = 0.0001). Repeated use of our stand-alone, smartphone-based VR exposure app reduces avoidance behavior and fear, providing a low-threshold treatment for fear of heights.

Effectiveness of a smartphone-based, augmented reality exposure app to reduce fear of spiders in real-life: A randomized controlled trial.

Although in vivo exposure therapy is highly effective in the treatment of specific phobias, only a minority of patients seeks therapy. Exposure to virtual objects has been shown to be better tolerated, equally efficacious, but the technology has not been made widely accessible yet. We developed an augmented reality (AR) application (app) to reduce fear of spiders and performed a randomized controlled trial comparing the effects of our app (six 30-min sessions at home over a two-week period) with no intervention. Primary outcome was subjective fear, measured by a Subjective Units of Distress Scale (SUDS) in a Behavioural Approach Test (BAT) in a real-life spider situation at six weeks follow-up. Between Oct 7, 2019, and Dec 6, 2019, 66 individuals were enrolled and randomized. The intervention led to significantly lower subjective fear in the BAT compared to the control group (intervention group, baseline: 7.12 [SD 2.03] follow-up: 5.03 [SD 2.19] vs. control group, baseline: 7.06 [SD 2.34], follow-up 6.24 [SD 2.21]; adjusted group difference -1.24, 95 % CI -2.17 to -0.31; Cohen's d = 0.57, p = 0.010). The repeated use of the AR app reduces subjective fear in a real-life spider situation, providing a low-threshold and low-cost treatment for fear of spiders.

Endogenous cortisol and conditioned placebo effects on pain - A randomized trial.

Placebo effects can be induced by learning and conditioning processes, which in turn are influenced and modulated by glucocorticoids. Accordingly, previous research has shown that intervention-related associative learning can be modulated through exogenous as well as endogenous glucocorticoids. Thus, the aim of this study was to elucidate whether placebo effects induced by conditioning is modulated by daily fluctuations of endogenous cortisol levels in healthy male and female subjects. Overall 77 participants underwent a two-phased placebo conditioning paradigm for pain analgesia. Subjects were randomized in two groups, which underwent placebo preconditioning either in the morning (08:00-10:00, i.e. with high endogenous cortisol levels) or in the afternoon (16:00-18:00, i.e. with low endogenous cortisol levels). Placebo effects were assessed two days later at noontime (12:00-13:00), with possible differences between groups as an indicator of glucocorticoid modulation on the placebo learning. Results indicated a significant conditioned placebo-induced analgesia, resulting in a placebo effect of small to medium size. Cortisol levels on conditioning day significantly differed between groups and cortisol levels were similar during assessment of placebo effects. Groups did not differ in their mean reduction in pain sensation, thus the placebo effect was not affected by differences in cortisol levels during the conditioning of placebo effects. The present study does not indicate a moderation of placebo conditioning by endogenous glucocorticoid levels.

Threat processing: models and mechanisms.

The experience of fear is closely linked to the survival of species. Fear can be conceptualized as a brain state that orchestrates defense reactions to threats. To avoid harm, an organism must be equipped with neural circuits that allow learning, detecting, and rapidly responding to threats. Past experience with threat can transform neutral stimuli present at the time of experience into learned threat-related stimuli via associative learning. Pavlovian threat conditioning is the central experimental paradigm to study associative learning. Once learned, these stimulus-response associations are not always expressed depending on context or new experiences with the conditioned stimuli. Neural circuits mediating threat learning have the inherent plasticity to adapt to changing environmental threats. Encounters devoid of danger pave the way for extinction or reconsolidation to occur. Extinction and reconsolidation can both lead to changes in the expression of threat-induced defense responses, but differ in stability and have a different neural basis. This review presents the behavioral models and the system-level neural mechanisms in animals and humans of threat learning and modulation.

Influence of stress on fear memory processes in an aversive differential conditioning paradigm in humans.

It is widely assumed that learning and memory processes play an important role in the pathogenesis, expression, maintenance and therapy of anxiety disorders, such as phobias or post-traumatic stress disorder (PTSD). Memory retrieval is involved in symptom expression and maintenance of these disorders, while memory extinction is believed to be the underlying mechanism of behavioral exposure therapy of anxiety disorders. There is abundant evidence that stress and stress hormones can reduce memory retrieval of emotional information, whereas they enhance memory consolidation of extinction training. In this study we aimed at investigating if stress affects these memory processes in a fear conditioning paradigm in healthy human subjects. On day 1, fear memory was acquired through a standard differential fear conditioning procedure. On day 2 (24h after fear acquisition), participants either underwent a stressful cold pressor test (CPT) or a control condition, 20 min before memory retrieval testing and extinction training. Possible prolonged effects of the stress manipulation were investigated on day 3 (48 h after fear acquisition), when memory retrieval and extinction were tested again. On day 2, men in the stress group showed a robust cortisol response to stress and showed lower unconditioned stimulus (US) expectancy ratings than men in the control group. This reduction in fear memory retrieval was maintained on day 3. In women, who showed a significantly smaller cortisol response to stress than men, no stress effects on fear memory retrieval were observed. No group differences were observed with respect to extinction. In conclusion, the present study provides evidence that stress can reduce memory retrieval of conditioned fear in men. Our findings may contribute to the understanding of the effects of stress and glucocorticoids on fear symptoms in anxiety disorders and suggest that such effects may be sex-specific.

Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications.

Current neurophysiological and psychological accounts view exposure therapy as the clinical analog of extinction learning that results in persistent modifications of the fear memory involved in the pathogenesis, symptomatology, and maintenance of anxiety disorders. Evidence from studies in animals and humans indicate that glucocorticoids have the potential to facilitate the processes that underlie extinction learning during exposure therapy. Particularly, glucocorticoids can restrict retrieval of previous aversive learning episodes and enhance consolidation of memory traces relating to non-fearful responding in feared situations. Thus, glucocorticoid treatment especially in combination with exposure therapy might be a promising approach to optimize treatment of anxiety disorders. This review examines the processes involved in aversive conditioning, fear learning and fear extinction, and how glucocorticoids might enhance restructuring of fear memories during therapy.