Exposure-based Therapy Research Articles

Virtual reality exposure-based therapy as an emerging treatment modality for anxiety disorders

Anxiety disorders are the most prevalent mental health condition, affecting one-third of the population during their lifetime. Patient with anxiety may experience overwhelming fear to an irrational fear that can impair everyday functioning. Current treatment for anxiety disorders include pharmacological (i.e. selective serotonin reuptake inhibitors) and psychological (i.e. cognitive behavioural therapy) intervention. Cognitive behavioural therapy is an effective exposure-based therapy utilizing repetitive exposure to the feared stimulus to develop desensitization and tolerance but holds high dropout rates due to unbearable anxiety for patients. Recognizing this challenge, virtual reality technology is emerging as a promising tool for patients to challenge their fear in a simulated environment based on individual progression. This article explores the new development of virtual reality technology as an effective treatment modality for anxiety disorders to enhance current approaches in mental health care.

A mechanistic model for individualised treatment of anxiety disorders based on predictive neural biomarkers.

Increased amygdala responsiveness is the hallmark of fear and a characteristic across patients with anxiety disorders. The amygdala is embedded in a complex regulatory circuit. Multiple different mechanisms may elevate amygdala responsiveness and lead to the occurrence of an anxiety disorder. While top-down control by the prefrontal cortex (PFC) downregulates amygdala responses, the locus coeruleus (LC) drives up amygdala activation via noradrenergic projections. This indicates that the same fearful phenotype may result from different neural mechanisms. We propose a mechanistic model that defines three different neural biomarkers causing amygdala hyper-responsiveness in patients with anxiety disorders: (a) inherent amygdala hypersensitivity, (b) low prefrontal control and (c) high LC drive. First-line treatment for anxiety disorders is exposure-based cognitive behavioural therapy, which strengthens PFC recruitment during emotion regulation and thus targets low-prefrontal control. A treatment response rate around 50% (Loerinc et al., 2015, Clinical Psychological Reviews, 42, 72-82) might indicate heterogeneity of underlying neurobiological mechanisms among patients, presumably leading to high variation in treatment benefit. Transforming insights from cognitive neuroscience into applicable clinical heuristics to categorise patients based on their underlying biomarker may support individualised treatment selection in psychiatry. We review literature on the three anxiety-related mechanisms and present a mechanistic model that may serve as a rational for pathology-based diagnostic and biomarker-guided treatment selection in psychiatry.

A Paradigm for Understanding Adolescent Social Anxiety with Unfamiliar Peers: Conceptual Foundations and Directions for Future Research

Adolescents who experience social anxiety concerns often display symptoms and impairments when interacting with unfamiliar peers. For adolescent clients, reducing symptoms and impairments within these interactions comprises a key treatment target within exposure-based therapies for social anxiety. Recent work on mechanisms of change in exposure-based therapies highlights the need for therapeutic exposures to simulate real-world manifestations of anxiety-provoking social situations. Yet, researchers encounter difficulty with gathering ecologically valid data about social interactions with unfamiliar peers. The lack of these data inhibits building an evidence base for understanding, assessing, and treating adolescent clients whose concerns manifest within these social interactions. Consequently, we developed a paradigm for understanding adolescent social anxiety within social interactions with unfamiliar peers. In this paradigm, we train peer confederates to interact with adolescents as if they were a same-age peer, within a battery of social interaction tasks that mimic key characteristics of therapeutic exposures. Leveraging experimental psychopathology and multi-modal assessment approaches, this paradigm allows for understanding core components of social interactions with unfamiliar peers relevant to exposure-based therapy, including stimuli variability, habituation, expectancy violations, peers' impressions about socially anxious adolescents, and maladaptive coping strategies that inhibit learning from exposures (e.g., safety behaviors). We detail the conceptual and empirical foundations of this paradigm, highlight important directions for future research, and report "proof of concept" data supporting these research directions. The Unfamiliar Peer Paradigm opens new doors for building a basic science that informs evidence-based services for social anxiety, within clinically relevant contexts in adolescents' social worlds.

Experience Versus Report: Where Are Changes Seen After Exposure-Based Cognitive-Behavioral Therapy? A Randomized Controlled Group Treatment of Childhood Social Anxiety Disorder

A considerable number of children and adolescents with social anxiety disorder (SAD) do not benefit from treatment as much as expected. However, treatment success should not be measured with social anxiety reports alone; the cognitive, behavioral, and physiological components of social stress should also be assessed. The authors examined an exposure-based SAD-specific group cognitive behavioral therapy (CBT) in a randomized controlled trial (N = 67, age 9–13 years, blind randomized allocation to treatment [CBT; n = 31] and waitlist control [WLC; n = 36] groups). Success was operationalized as a clinically significant reduction of symptoms measured with SAD-specific questionnaires, structured interviews, and changes in response to the Trier Social Stress Test (TSST). In the CBT group, there was a trend toward a significant increase in positive cognitions in the TSST after treatment (d = 0.37), whereas these positive cognitions decreased in the WLC group (d = 0.40). No significant results involving group appeared for negative cognitions, behavior and physiology. Children in the CBT group, but not parents, further reported less social anxiety in one questionnaire from pre- to post-treatment (d = 0.89). A structured interview confirmed a decrease in severity of SAD in the CBT group. While the gold standard of a blind interview showed efficacy of treatment, not all trait and state measures demonstrated similar success patterns.Trial registration Eligibility criteria and some of the dependent variables (cognitions, physiology) for treatment success were registered with the German Research Foundation (TU 78/5-2, HE 3342/4-2) prior to recruitment. Clinical assessment of diagnosis and behavioral data were not a priori planned as outcome measures for this trial and therefore analyzed in a post-hoc approach.

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder

BackgroundOnly 40–60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of “personalized medicine.” Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder.Methods/designWe are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder–7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods.DiscussionThis protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome.Trial registrationThe study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.

Virtual Reality and Symptoms Management of Anxiety, Depression, Fatigue, and Pain: A Systematic Review.

In recent years, virtual reality (VR) has become an interesting alternative to traditional exposure-based therapies for many symptoms. VR involves immersion in a computer-generated virtual environment that minimizes avoidance and facilitates emotional processing. The objective of this systematic review is to evaluate evidence on the intervention effect of VR on anxiety, depression, fatigue, and pain. The research strategy of this systematic review included three electronic databases (MEDLINE/PubMed, Cochrane Library, and ScienceDirect) based on predetermined inclusion and exclusion criteria. Published quantitative studies from 2000 to 2020 were identified, which examined the effect of VR intervention on four different symptoms related to symptoms experienced by cancer patients. Quality assessments, data extractions, and analysis were completed on all included studies. A total of 882 titles and abstracts were screened, and 23 studies were included in the review. The studies were grouped according to the symptoms: anxiety and depression, fatigue, and pain. The review showed that VR intervention is more effective compared with the control (i.e., standard care) for anxiety, depression, fatigue, and pain. VR can reduce effectively these symptoms in different contexts and diseases, including cancer. The evidence suggests that there is value in exploring this intervention as a potential crossover treatment for these symptoms in patients. This study contributes to evidence that distraction is an effective symptom management mechanism. The findings are congruent with the theoretical framework, supporting the premise that VR, as an emotion-focused distraction intervention, decreases the severity of these symptoms.

Bright light exposure augments cognitive behavioral therapy for panic and posttraumatic stress disorders: a pilot randomized control trial

Bright light (BL) therapy is clinically utilized for treatment of sleep–wake disorders through the manipulation of circadian oscillation. It is also extended to depressive disorders including seasonal affective disorder through emotional regulation. Recently, it has been suggested that BL facilitates memory encoding and consolidation via another psychophysiological mechanism of perceptual information processing in the brain. In particular, BL can help to alleviate stress associated with processing of fear memories. In this study, we explored a potential application of BL for treatment of stress-induced and fear circuitry disorders in patients receiving exposure-based cognitive behavioral therapy (CBT). Fourteen patients with panic disorder (PD) or posttraumatic stress disorder (PTSD) were enrolled in a single-blind, randomized control trial to assess BL exposure (8000-lux, 30 min, 9 times, 2 weeks apart) compared to sham light (SL) exposure (800-lux, the same duration and frequency), while patients were concurrently receiving exposure-based CBT. The State Trait Anxiety Index (STAI) and the self-rating version of Montgomery–Asberg Depression Rating Scale (MADRS-S) assessed anxiety-related severity scores before and after therapy. After dropouts, 10 participants remained. STAI and MADRS-S scores showed a significantly greater reduction in the BL group than in the SL group. BL may be an effective augmentative therapy when used with exposure-based CBT for PD and PTSD patients. Future trials with larger sample sizes that are adequately statistically powered are required to confirm these preliminary findings.

Clinician-reported barriers to using exposure with response prevention in the treatment of paediatric obsessive-compulsive disorder

Exposure techniques are underutilised in the treatment of anxiety disorders in routine practice, but little is known about the use of exposure with response prevention (ERP) for OCD, particularly in youth. The current study aimed to examine the utilisation of ERP for paediatric OCD via an anonymous online survey completed by clinicians (N = 107). Specifically, we explored the association of clinician characteristics and OCD symptom subtypes with ERP use, as well as clinician-reported barriers to ERP implementation. The majority of clinicians reported commonly using ERP when treating youth with OCD, and rates of ERP use were highest among clinical psychologists. Clinician-held negative beliefs about exposure were significantly associated with lower ERP use. Additionally, clinicians reported being less likely to use ERP to treat hoarding symptoms and taboo obsessions, compared to other OCD symptom subtypes. The most commonly endorsed barriers to successful ERP implementation were aspects of the phenomenology of OCD (e.g. covert compulsions, frequently changing rituals) as opposed to general barriers (e.g. insufficient time during sessions). Overall, our findings suggest that OCD presents unique challenges for clinicians delivering exposure-based therapy. Training should address these OCD-specific obstacles in order to promote dissemination of ERP for youth with OCD.

Distinct trajectories of long-term symptom severity in pediatric obsessive-compulsive disorder during and after stepped-care treatment.

First-line treatments for pediatric obsessive-compulsive disorder (OCD) include exposure-based cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). No studies have thus far identified distinct classes and associated predictors of long-term symptom severity during and after treatment. Yet, these could form the basis for more personalized treatment in pediatric OCD. The study included 269 OCD patients aged 7-17years from the Nordic Long-term OCD Treatment Study (NordLOTS). All participants received stepped-care treatment starting with 14 weekly sessions of manualized CBT. Nonresponders were randomized to either prolonged CBT or SSRIs. Symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale at seven time points from pre- to post-treatment and over a three-year follow-up. Latent class growth analysis (LCGA) was performed to identify latent classes of symptom severity trajectories. Univariate and multivariate analyses were used to detect differences between classes and identify predictors of trajectory class membership including several clinical and demographic variables. Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119. Three LCGA classes were identified: (a) acute, sustained responders (54.6%); (b) slow, continued responders (23.4%); and (c) limited long-term responders (21.9%). Class membership was predicted by distinct baseline characteristics pertaining to age, symptom severity, contamination/cleaning and anxiety symptoms. The LCGA suggests three distinct trajectory classes of long-term symptom severity during and after treatment in pediatric OCD with different clinical profiles at pretreatment. The results point to required clinical attention for adolescent patients with contamination/cleaning and anxiety symptoms who do not show convincing responses to first-line treatment even though they may have reached the established cutoff for treatment response.

Vagus nerve stimulation produces immediate dose-dependent anxiolytic effect in rats

BackgroundChronic vagus nerve stimulation (VNS) attenuates anxiety in rats and humans. However, it is unclear whether VNS can promote acute anxiolytic effects. Here we examined short-term anxiolytic effects of VNS using single or multiple trains in rats submitted to a battery of tests. MethodsThree groups of rats were implanted with VNS cuffs and tested for anxiety using the elevated plus maze (EPM), novelty suppressed feeding (NSF), and acoustic startle response (ASR), after receiving either one or five VNS trains (0.4 mA/30 Hz/30‑sec), or sham stimulation. ResultsBoth single and multiple VNS trains reduced state anxiety as measured using the EPM, but only multiple trains reduced anxiety in the EPM and NSF. VNS did not decrease arousal as measured using the ASR. LimitationsThe anxiolytic effects of VNS may be differently influenced by test order or prior-exposure to stress. VNS did not affect startle responses in naïve rats but the present findings do not determine whether VNS would affect startle responses that are potentiated by fear or anxiety. ConclusionA single VNS train can produce an anxiolytic-like effect in the EPM minutes later, an effect that is not observed in the NSF. Delivering 5 VNS trains restores the immediate effects across tests of anxiety, indicating that more trains produce a more robust anxiolytic effect. The lack of effects on ASR suggests that VNS affects state anxiety but not baseline arousal in naïve rats. We suggest that the anxiolytic effect of VNS can increase tolerability and reduce dropout in exposure-based therapies.

Is it time to rethink standard dosage of exposure-based cognitive behavioral therapy for pediatric obsessive-compulsive disorder?

ObjectiveIdentifying factors associated with early treatment response is important, because it can help allocate limited resources in psychiatric care more appropriately. This study examined baseline characteristics of participants with early response to exposure-based cognitive behavior therapy (CBT) for pediatric obsessive-compulsive disorder (OCD). Method269 participants with OCD, aged 7–17 years, were enrolled in a 14-weeks CBT program. We identified participants with early response to treatment, (CY-BOCS total score of ≤15), by the seventh session. ResultsAt week 7, 248 (92.2%) participants were assessed, 38.3% (95% CI 32.4–44.5%, n = 95) were identified as treatment responders. Univariate analyses showed that six baseline characteristics were significantly associated with early treatment response: young age, lower levels of symptom severity, functional impairment, internalizing- and externalizing problems, depressive symptoms, and family accommodation. ConclusionsThese results suggested that treatment plans for younger children with moderate OCD symptoms and no major comorbid disorder should include briefer and less resource demanding treatment formats than the commonly recommended and applied standard doses of 15 CBT sessions.

Acceptance-based interventions in the treatment of PTSD: Group and individual pilot data using Acceptance and Commitment Therapy

Acceptance and Commitment Therapy (ACT) is a principle-based behavioral intervention that addresses human suffering using mindfulness and acceptance techniques along with behavioral commitments linked to personal values. While ACT has been applied to a wide variety of problems, it is well suited to the treatment of trauma based on its processes specifically designed to reduce experiential avoidance, and it has only just begun to be investigated for its effectiveness with this population. Furthermore, current drop-out and refusal rates for exposure-based therapies, the main empirically supported intervention for the treatment of posttraumatic stress disorder (PTSD), necessitate the development of alternatives. The current pilot studies evaluated a 12-session group ACT intervention with 10 veterans diagnosed with PTSD, and a 12-session individual ACT intervention with 9 veterans diagnosed with PTSD. Significant reductions in PTSD symptoms from pre to post or follow-up were found for both the group intervention (n = 10, g = 0.69) and the individual intervention (n = 9; g = 1.24). Decreases in thought suppression as well as increases in aspects of mindfulness and psychological flexibility were also found, but results were mixed and differed by the individual versus group intervention.

Devaluation of threat memory using a dual-task intervention does not reduce context renewal of fear

Many patients who benefit from exposure-based therapy for anxiety disorders fail to maintain their gains. Learned fear may return when they encounter phobic stimuli in a different context than the one in which extinction occurred. In the current pre-registered experiment, we tested whether threat memory devaluation reduces context renewal of fear. A dual-task intervention was used to devalue threat memory. During this intervention, individuals recall the threat memory while simultaneously performing a demanding secondary task (e.g., making eye movements). On day 1, participants (N = 75) underwent fear acquisition with an aversive film clip in context A. On day 2, 25 participants were assigned to each group, namely a dual-task group, or one of two control groups: recall only task (without the dual-task) or no intervention. Afterwards, all participants underwent extinction training in context B and were then exposed to context A again in a test phase. The dual-task intervention effectively degraded threat memory compared to no intervention, but the recall only intervention was also partly effective. However, all three groups showed comparable fear renewal on subjective and physiological measures. This indicates that threat memory devaluation was not effective to prevent context renewal.

Association of rs7688285 allelic variation coding for GLRB with fear reactivity and exposure-based therapy in patients with panic disorder and agoraphobia

The gene coding for glycine receptor β subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk») in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.

The Impact of Psychological Interventions on Posttraumatic Stress Disorder and Pain Symptoms: A Systematic Review and Meta-Analysis.

Posttraumatic stress disorder (PTSD) and pain often co-occur, introducing clinical challenges and economic burden. Psychological treatments are considered effective for each condition, yet it is not known which therapies have the potential to concurrently address PTSD and pain-related symptoms. To conduct a systematic review and meta-analysis, databases were searched for articles published between January 2007 and December 2017 describing results from clinical trials of interventions addressing PTSD and pain-related symptoms in adults. Two independent reviewers finalized data extraction and risk of bias assessments. A random-effects model was used for meta-analysis and to calculate pooled and subgroup effect sizes (ESs) of psychological-only (single modality) and multimodal interventions. Eighteen trials (7 uncontrolled, 11 randomized controlled trials, RCTs), totaling 1583 participants, were included in the systematic review. RCT intervention types included exposure-based, cognitive-behavioral, and mindfulness-based therapies. Data from 10 RCTs (N=1, 35) were available for meta-analysis, which demonstrated moderate effect for reduced PTSD severity (ES=-0.55, confidence interval [CI]: -0.83, -0.26) and nonsignificant effect for pain intensity (ES=-0.14, CI: -0.43, 0.15) and pain interference (ES=-0.07, CI: -0.35, 0.20) outcomes. Findings from uncontrolled trials supported meta-analytic results from RCTs. Using GRADE assessment, the quality of evidence was deemed as moderate for RCTs and low for non-RCTs. Findings indicated that the majority of the interventions appeared to have a greater impact on reducing PTSD rather than pain-related symptoms. There remains a need to further develop interventions that consistently impact PTSD and pain-related outcomes when these 2 conditions co-occur.

The effects of stress on exposure-based therapy outcome

The effects of stress on exposure-based therapy outcome

L-DOPA improves extinction memory retrieval after successful fear extinction

RationaleA promising strategy to prevent a return of fear after exposure-based therapy in anxiety disorders is to pharmacologically enhance the extinction memory consolidation presumed to occur after exposure. Accumulating evidence suggests that the effect of a number of pharmacological consolidation enhancers depends on a successful fear reduction during exposure. Here, we employed the dopamine precursor L-DOPA to clarify whether its documented potential to enhance extinction memory consolidation is dependent on successful fear extinction.MethodsIn two double-blind, randomized and placebo-controlled experiments (experiment 1: N = 79, experiment 2: N = 32) comprising fear conditioning (day 1), extinction followed by administration of 150 mg L-DOPA or placebo (day 2) and a memory test (day 3) in healthy male adults, conditioned responses were assessed as differential skin conductance responses. We tested whether the effect of L-DOPA on conditioned responses at test depended on conditioned responses at the end of extinction in an experiment with a short (10 trials, experiment 1) and long (25 trials, experiment 2) extinction session.ResultsIn both experiments, the effect of L-DOPA was dependent on conditioned responses at the end of extinction. That is, post-extinction L-DOPA compared to placebo administration reduced conditioned responses at test only in participants showing a complete reduction of conditioned fear at the end of extinction.ConclusionThe results support the potential use of L-DOPA as a pharmacological adjunct to exposure treatment, but point towards a common boundary condition for pharmacological consolidation enhancers: a successful reduction of fear in the exposure session.

Internet-delivered psychological treatment for patients with health anxiety: Results from a randomized, controlled trial

Self-rated health (SRH) has been shown to be a stable predictor of illness and mortality. Improvement in SRH, even in the absence of change in objective health, predicts better health and reduced mortality. Severe health anxiety (SHA) is characterized by fear of illness and distorted health perception. The objective of the present study was to investigate if exposure-based cognitive behavior therapy (CBT) for SHA can lead to improvement in SRH and whether this improvement is mediated by reduced health anxiety.Data were collected from a randomized controlled trial where participants with SHA were allocated to 12 weeks of exposure-based CBT (n = 99) for SHA or to a no treatment control condition (n = 33). The mediation analysis was based on SRH- and health anxiety data collected weekly during the treatment phase.Linear mixed effects models analysis showed a significant interaction effect of group and time indicating superior improvements in SRH in exposure-based CBT compared to the control condition (Z = 2.69, p = 0.007). The controlled effect size was moderately large (d = 0.64) and improvements were stable at 1-year follow-up. Reduced health anxiety was a significant mediator of improvement in SRH.12 weeks of exposure-based CBT for SHA can lead to significant improvements in SRH. Considering the previously established importance of SRH as a predictor for disease and mortality, exposure-based CBT for severe health anxiety may lead to improvements on several important health parameters, possibly even increasing the likelihood of longevity.

Exposure-Based Cognitive-Behavioral Therapy for Disruptive Mood Dysregulation Disorder: An Evidence-Based Case Study

Severe, chronic irritability is one of the most frequently reported problems in youth referred for psychiatric care. Irritability predicts adult depressive and anxiety disorders, and long-term impairment. Reflecting this pressing public health need, severe, chronic, and impairing irritability is now codified by the DSM-5 diagnosis of disruptive mood dysregulation disorder (DMDD). Since DMDD has only recently been added as its own nosological class, efficacious treatments that specifically target severe irritability as it presents in DMDD are still being developed. In a recent pilot study, we described the general concept of exposure-based cognitive-behavioral therapy (CBT) for irritability. This mechanism-driven treatment is based on our pathophysiological model of irritability that postulates two underlying mechanisms, which potentiate each other: (1) heightened reactivity to frustrative nonreward, and (2) aberrant approach responses to threat. In this case report, we describe and illustrate the specific therapeutic techniques used to address severe irritability in an 11-year-old boy with a primary diagnosis of DMDD. Specific techniques within this CBT include motivational interviewing to build commitment and target oppositionality; creation of an anger hierarchy; in-session controlled, gradual exposure; and parent training focusing on contingency management to counteract the instrumental learning deficits in irritable youth. Parents learn to tolerate their own emotional responses to their youth’s irritability (e.g., parents engage in their own exposure) and increase their adaptive contingencies for their youth’s behavior (e.g., withdraw attention during unwanted behavior, praise desirable behavior). Future directions in the context of this CBT, such as leveraging technology, computational modeling, and pathophysiological targets, are discussed.

T29. Neural Correlates of Safety Cue Learning in Children With and Without Anxiety Disorders

Exposure-based therapy for pediatric anxiety is based on principles of fear learning and extinction. Animal studies have shown that presenting threat and safety cues simultaneously (conditioned inhibition) may be a promising approach to augment fear reduction. Here, we investigate the neural correlates of fear and safety cue learning in children with and without anxiety disorders.