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Maladaptive safety behavior maintains fear and anxiety by prohibiting inhibitory learning about the non-occurrence of feared outcomes (known as protection from extinction). Not engaging in safety behavior, however, requires to act opposite to fear-motivated behavioral tendencies. The initiation of such fear-opposite action by positive outcomes, which were in conflict with safety behavior, was tested. Following fear acquisition to a warning signal (CS+), participants acquired safety behavior to prevent the aversive outcome (n = 48). Next, safety behavior also prevented gaining rewards. In a control group (n = 50), neutral outcomes were presented to control for novelty effects of the second outcome. Subsequently, no aversive outcome occurred anymore. Phases with safety behavior were intermitted by phases without safety behavior being available to examine cognitive and physiological indicators of fear and anxiety. Without competing positive outcomes, safety behavior was frequently executed, persisted in absence of the aversive outcome, and prohibited extinction learning. Positive outcomes clearly reduced safety behavior despite equal levels of acquired fear. This enabled fear extinction as soon as the aversive outcome was absent. Importantly, this extinction learning resulted in attenuated fear and anxiety responses when safety behavior became unavailable. Post-hoc findings indicated that the mere anticipation of positive outcomes slightly reduced safety behavior. Thus, competing positive outcomes triggered fear-opposite action that prevented persistent safety behavior and protection from extinction.

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Background: Pathological avoidance is a transdiagnostic characteristic of anxiety disorders. Avoidance conditioning re-emerged as a translational model to examine mechanisms and treatment of avoidance. However, its validity for anxiety disorders remains unclear. Methods: This study tested for altered avoidance in patients with anxiety disorders compared to matched controls (n = 40/group) using instrumental conditioning assessing low-cost avoidance (avoiding a single aversive outcome) and costly avoidance (avoidance conflicted with gaining rewards). Autonomic arousal and threat expectancy were assessed as indicators of conditioned fear. Associations with dimensional symptom severity were examined. Results: Patients and controls showed frequent low-cost avoidance without group differences. Controls subsequently inhibited avoidance to gain rewards, which was amplified when aversive outcomes discontinued. In contrast, patients failed to reduce avoidance when aversive and positive outcomes competed (elevated costly avoidance) and showed limited reduction when aversive outcomes discontinued (persistent costly avoidance). Interestingly, elevated costly avoidance was not linked to higher conditioned fear in patients. Moreover, individual data revealed a bimodal distribution of costly avoidance: Some patients showed persistent avoidance, others showed little to no avoidance. Persistent versus low avoiders did not differ in other task-related variables, response to gains and losses in absence of threat, sociodemographic data, or clinical characteristics. Conclusions: Findings suggest that anxious psychopathology is associated with a deficit to inhibit avoidance in presence of competing positive outcomes. This offers novel perspectives for research on mechanisms and treatment of anxiety disorders.

Background: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. Methods: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. Results: Both treatments resulted in substantial improvements at post (PeEx-I: dwithin  = 1.50, PeEx-S: dwithin  = 1.78) and follow-up (PeEx-I: dwithin = 2.34; PeEx-S: dwithin = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TRPeEx-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. Conclusions: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.

Despite striking empirical support, exposure-based treatments for anxiety disorders are underutilized. This is partially due to clinicians’ concerns that patients may reject exposure or experience severe side effects, particularly in intensive forms of exposure. We examined acceptance and side effects of two randomly assigned variants of prediction error-based exposure treatment differing in temporal density (1 vs. 3 sessions/week) in 681 patients with panic disorder, agoraphobia, social anxiety disorder, and multiple specific phobias. Treatment acceptance included treatment satisfaction and credibility, engagement (i.e., homework completion) and tolerability (i.e., side effects, dropout and perceived treatment burden). Side effects were measured with the Inventory for the Balanced Assessment of Negative Effects of Psychotherapy (INEP). We found treatment satisfaction, credibility, and engagement to be equally high in both variants of exposure-based treatment, despite higher treatment burden (β = 0.25) and stronger side effects (β = 0.15) in intensified treatment. 94.1% of patients reported positive effects in the INEP. 42.2% reported side effects, with treatment stigma (16.6%), low mood (14.8%) and the experience to depend on the therapist (10.9%) being the most frequently reported. The mean intensity of side effects was low. We conclude that prediction error-based exposure treatment is well accepted by patients with different anxiety disorders and that patients also tolerate temporally intensified treatment, despite higher perceived treatment burden and stronger side effects. Clinicians should be aware of the most frequent side effects to take appropriate countermeasures. In sum, temporal intensification appears to be an acceptable strategy to achieve faster symptom reduction, given patients’ well-informed consent.

The so-called ‘replicability crisis’ has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence-based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.

Avoidance habits potentially contribute to maintaining maladaptive, costly avoidance behaviors that persist in the absence of threat. However, experimental evidence about costly habitual avoidance is scarce. In two experiments, we tested whether extensively trained avoidance impairs the subsequent goal-directed approach of rewards. Healthy participants were extensively trained to avoid an aversive outcome by performing simple responses to distinct full-screen color stimuli. After the subsequent devaluation of the aversive outcome, participants received monetary rewards for correct responses to neutral object pictures, which were presented on top of the same full-screen colors. These approach responses were either compatible or incompatible with habitual avoidance responses. Notably, the full-screen colors were not relevant to inform approach responses. In Experiment 1, participants were not instructed about post-devaluation stimulus-response-reward contingencies. Accuracy was lower in habit-incompatible than in habit-compatible trials, indicating costly avoidance, whereas reaction times did not differ. In Experiment 2, contingencies were explicitly instructed. Accuracy differences disappeared, but reaction times were slower in habit-incompatible than in habit-compatible trials, indicating low-cost habitual avoidance tendencies. These findings suggest a small but consistent impact of habitual avoidance tendencies on subsequent goal-directed approach. Costly habitual responding could, however, be inhibited when competing goal-directed approach was easily realizable.

Conflicts between avoiding feared stimuli versus approaching them for competing rewards are essential for functional behavior and anxious psychopathology. Yet, little is known about the underlying decision process. We examined approach-avoidance decisions and their temporal dynamics when avoiding Pavlovian fear stimuli conflicted with gaining rewards. First, a formerly neutral stimulus (CS+) was repeatedly paired with an aversive stimulus (US) to establish Pavlovian fear. Another stimulus (CS−) was never paired with the US. A control group received neutral tones instead of aversive USs. Next, in each of 324 trials, participants chose between a CS−/low reward and a CS+/high reward option. For the latter, probability of CS+ presentation (Pavlovian fear information) and reward magnitude (reward information) varied. Computer mouse movements were tracked to capture the decision dynamics. Although no more USs occurred, pronounced and persistent costly avoidance of the Pavlovian fear CS+ was found. Time-continuous multiple regression of movement trajectories revealed a stronger and faster impact of Pavlovian fear compared to reward information during decision-making. The impact of fear information, but not reward information, modestly decreased across trials. These findings suggest a persistently stronger weighting of fear compared to reward information during approach-avoidance decisions, which may facilitate the development of pathological avoidance.

Individual responses to behavioral treatment of anxiety disorders vary considerably, which requires a better understanding of underlying processes. In this study, we examined the violation and change of threat beliefs during exposure. From 8,484 standardized exposure records of 605 patients with different anxiety disorders, learning indicators were derived: expectancy violation as mismatch between threat expectancy before exposure and threat occurrence, expectancy change as difference between original and adjusted expectancy after exposure, and prediction-error learning rate as extent to which expectancy violation transferred into change. Throughout sessions, high threat expectancy but low occurrence and adjusted expectancy indicated successful violation and change of threat beliefs by exposure. Expectancy violation, change, and learning rate substantially varied between patients. Not expectancy violation itself, but higher learning rate and expectancy change predicted better treatment outcome. Successful exposure thus requires expectancy violation to induce actual expectancy change, supporting learning from prediction error as transdiagnostic mechanism underlying successful exposure therapy.

Recent studies on reward-based decision-making in the presence of anxiety-related stimuli demonstrated that approach-avoidance conflicts can be assessed under controlled laboratory conditions. However, the clinical relevance of these decision conflicts has not been demonstrated. To this end, the present study investigated avoidant decisions in treatment-seeking individuals with social anxiety disorder (SAD). In a gambling task, advantageous choices to maximize gains were associated with task-irrelevant angry faces and disadvantageous choices with happy faces. The clinical relevance of avoidant decisions for in vivo anxiety in a social stress situation (public speaking) were examined (n = 44). In a subsample (n = 20), the predictive value for a reduction of avoidance following behavioral therapy was also evaluated. Results indicated a close link between more frequent avoidant decisions and elevated in vivo anxiety. Moreover, individuals who showed a deficit in the goal-directed adjustment of their decisions also showed higher and sustained distress during the social stressor and reported less decrease of avoidance following treatment. The findings highlight the importance of an avoidant decision-making style for the experience of acute distress and the maintenance of avoidance in SAD. Assessing avoidant decision-making may help to predict the response to behavioral treatments.

Recent research indicates that angry facial expressions are preferentially processed and may facilitate automatic avoidance response, especially in socially anxious individuals. However, few studies have examined whether this bias also expresses itself in more complex cognitive processes and behavior such as decision making.We recently introduced a variation of the Iowa Gambling Task which allowed us to document the influence of taskirrelevant emotional cues on rational decision making. The present study used a modified gambling task to investigate the impact of angry facial expressions on decision making in 38 individuals with a wide range of social anxiety. Participants were to find out which choices were (dis-) advantageous to maximize overall gain. To create a decision conflict between approach of reward and avoidance of fear-relevant angry faces, advantageous choices were associated with angry facial expressions, whereas disadvantageous choices were associated with happy facial expressions. Results indicated that higher social avoidance predicted less advantageous decisions in the beginning of the task, i.e., when contingencies were still uncertain. Interactions with specific skin conductance responses further clarified that this initial avoidance only occurred in combination with elevated responses before choosing an angry facial expressions. In addition, an interaction between high trait anxiety and elevated responses to early losses predicted faster learning of an advantageous strategy. These effects were independent of intelligence, general risky decision-making, self-reported state anxiety, and depression. Thus, socially avoidant individuals who respond emotionally to angry facial expressions are more likely to show avoidance of these faces under uncertainty. This novel laboratory paradigm may be an appropriate analog for central features of social anxiety.

Fear motivates different types of defensive behaviors. These behaviors are, however, not mere byproducts of fear. In this review, we highlight a bi-directional relationship between conditioned fear and instrumental defensive behavior in humans. We discuss mechanisms involved in the link from fear to goal-directed avoidance (e.g., relief, generalization), that may become habitual. These defensive behaviors may in turn reduce, preserve, or amplify fear responding (e.g., protection-from-extinction, behavior-as-information). Multiple factors moderate the bi-directional relationship. Evidence for amplifying and dampening effects of inter-individual differences (e.g., trait anxiety, distress tolerance), intra-individual states (e.g., stress), and external factors (e.g., incentives for competing behavior) on goal-directed and/or habitual defensive behavior is reviewed. However, the exact mechanisms by which these factors moderate the bi-directional relationship are still largely unknown (e.g., modulating avoidance directly vs. indirectly via conditioned fear). Finally, we discuss major implications: First, understanding factors moderating the bi-directional relationship provides insights into risk and resilience factors for anxious psychopathology. Second, specific experimental models and clinical interventions can be mapped onto distinct defensive behaviors (e.g., goal-directed vs. habitual avoidance). More precise matching will help to develop nuanced models and interventions to reduce pathological behaviors and individualize treatments.

Systematic and quantitative reviews on the effects of land-based self-exclusion are scarce. Therefore, the current review aimed to provide a comprehensive summary of (1) the demographic characteristics of land-based self-excluders and changes after exclusion, including (2) gambling behavior, (3) gambling problems, (4) mental symptoms, and (5) mental health. A systematic database and literature search was performed following PRISMA guidelines. Nineteen naturalistic studies met the eligibility criteria. The quality of all included records was rated via adaption of the Newcastle-Ottawa Scale. Results from higher-quality records were more heavily weighted. Self-excluders were predominantly men in their early or middle forties. Changes after exclusion revealed wide ranges in the rates of abstinence (13-81%), rates of gambling reduction (29-92%), and rates of exclusion breaches (8-59%). The records consistently demonstrated significant changes in pathological gambling from before exclusion (61–95%) to after exclusion (13–26%). Up to 73% of self-excluders exhibited symptoms of anxiety, depression, and substance use disorders at program enrollment. Several aspects of mental health improved after exclusion, e.g., quality of life. Problem and pathological gambling are most prevalent in young men, but self-exclusion was most prominent in middle-aged men. The magnitude of effects widely differed between studies despite overall benefits of self-exclusion, and many individuals continued gambling after exclusion. This shortcoming could be minimized using improved access controls and the extension of exclusion to other gambling segments. High rates of pathological gambling and other mental disorders in self-excluders highlight the need for improved early detection and treatment accessibility.

Safety behavior prevents the occurrence of threat, thus it is typically considered adaptive. However, safety behavior in anxiety-related disorders is often costly, and persists even the situation does not entail realistic threat. Individuals can engage in safety behavior to varying extents, however, these behaviors are typically measured dichotomously (i.e., to execute or not). To better understand the nuances of safety behavior, this study developed a dimensional measure of safety behavior that had a negative linear relationship with the admission of an aversive outcome. In two experiments, a Reward group receiving fixed or individually calibrated incentives competing with safety behavior showed reduced safety behavior than a Control group receiving no incentives. This allowed extinction learning to a previously learnt warning signal in the Reward group (i.e., updating the belief that this stimulus no longer signals threat). Despite the Reward group exhibited extinction learning, both groups showed a similar increase in fear to the warning signal once safety behavior was no longer available. This null group difference was due to some participants in the Reward group not incentivized enough to disengage from safety behavior. Dimensional assessment revealed a dissociation between low fear but substantial safety behavior to a safety signal in the Control group. This suggests that low-cost safety behavior does not accurately reflect the fear-driven processes, but also other non-fear-driven processes, such as cost (i.e., engage in safety behavior merely because it bears little to no cost). Pinpointing both processes is important for furthering the understanding of safety behavior.

Avoidance is typically adaptive given it prevents threat. However, avoidance becomes maladaptive when it is executed out of proportion of threat (i.e., excessive or insufficient avoidance), persists in the absence of threat, or excessively generalizes to other innocuous situations. Although there has been an increase in research in these different processes of maladaptive avoidance, the role of inter-individual differences in these avoidance processes receives less research attention, despite its theoretical and clinical importance. In this systematic review, we summarized the role of inter-individual traits that relate to risk or resilient factors for anxiety-related disorders, trauma-and stressor-related disorders, obsessive-compulsive related disorders, pain related disorders, eating-related disorders, and affective disorders. A majority of the inter-individual differences had an apparent mixed or null effect on the different processes of avoidance. We discussed this lack of evidence of inter-individual differences on avoidance due to a lack of methodological and/or analytical consensus in the field, in addition to a lack of integration of recent findings into existing theories. Recommendations for future research are discussed, with a focus on examining the conditions or experimental parameters for certain inter-individual traits to manifest their effects on avoidance, identifying the nuances of methodological and/or inter-individual differences in avoidance, and a call for integrating recent preliminary findings into existing theories.

Background: Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders. Methods: Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP). Results: The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: β = −0.35; NVS: β = 0.39; CS: β = −0.12; SP: β = −0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association. Limitations: The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for. Conclusion: Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.