Differentiating neural sensitivity and bias during face-emotion processing in youth: a computational approach.

The ability to interpret face-emotion displays is critical for the development of adaptive social interactions. Using a novel variant of a computational model and fMRI data, we examined behavioral and neural associations between two metrics of face-emotion labeling (sensitivity and bias) and age in youth. Youth and adults (n = 44, M age = 20.02, s.d. = 7.44, range = 8-36) completed an explicit face-emotion labeling fMRI task including happy to angry morphed face emotions. A drift-diffusion model was applied to choice and reaction time distributions to examine sensitivity and bias in interpreting face emotions. Model fit and reliability of parameters were assessed on adult data (n = 42). Linear and quadratic slopes modeled brain activity associated with dimensions of face-emotion valence and ambiguity during interpretation. Behaviorally, age was associated with sensitivity. The bilateral anterior insula exhibited a more pronounced neural response to ambiguity with older age. Associations between sensitivity and bias metrics and activation patterns indicated that systems encoding face-emotion valence and ambiguity both contribute to the ability to discriminate face emotions. The current study provides evidence for age-related improvement in perceptual sensitivity to facial affect across adolescence and young adulthood.

Weight gained during treatment predicts 6-month body mass index in a large sample of patients with anorexia nervosa using ensemble machine learning.

OBJECTIVE: This study used machine learning methods to analyze data on treatment outcomes from individuals with anorexia nervosa admitted to a specialized eating disorders treatment program. METHODS: Of 368 individuals with anorexia nervosa (209 adolescents and 159 adults), 160 individuals had data available for a 6-month follow-up analysis. Participants were treated in a 6-day-per-week partial-hospital program. Participants were assessed for eating disorder-specific and non-specific psychopathology. The analyses used established machine learning procedures combined in an ensemble model from support vector machine learning, random forest prediction, and the elastic net regularized regression with an exploration (training; 75%) and confirmation (test; 25%) split of the data. RESULTS: The models predicting body mass index (BMI) at 6-month follow-up explained a 28.6% variance in the training set (n = 120). The model had good performance in predicting 6-month BMI in the test dataset (n = 40), with predicted BMI significantly correlating with actual BMI (r = .51, p = 0.01). The change in BMI from admission to discharge was the most important predictor, strongly correlating with reported BMI at 6-month follow-up (r = .55). Behavioral variables were much less predictive of BMI outcome. Results were similar for z-transformed BMI in the adolescent-only group. Length of stay was most predictive of weight gain in treatment (r = .56) but did not predict longer-term BMI. CONCLUSIONS: This study, using an agnostic ensemble machine learning approach in the largest to-date sample of individuals with anorexia nervosa, suggests that achieving weight gain goals in treatment predicts longer-term weight-related outcomes. Other potential predictors, personality, mood, or eating disorder-specific symptoms were relatively much less predictive. PUBLIC SIGNIFICANCE: The results from this study indicate that the amount of weight gained during treatment predicts BMI 6 months after discharge from a high level of care. This suggests that patients require sufficient time in a higher level of care treatment to meet their specific weight goals and be able to maintain normal weight.

Irritability in Youths: A Critical Integrative Review.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

Editorial: The EDI-YC: A New Measure of Emotion Dysregulation in Young Children.

Although emotion dysregulation is at a peak during the preschool age (2-5 years) and clinically significant dysregulation has impact across the lifespan, there are surprisingly few ways to measure it in this age group. This is especially true for groups of children in whom emotion may be particularly dysregulated, such as those with autism spectrum disorder. The modern, rigorous development of a well-grounded measure has profound clinical implications. Practically, it gives a common reference for the severity of a clinical issue, which is the foundation of measurement-based care and quantitative research. Theoretically, the process also defines the issue involving the scale designers, those whom the scale is about, and even the scale users as the measure is used and refined over years. Measures of preschool emotion dysregulation will allow us to better map its trajectory from preschool throughout the lifespan. In this issue, Day and Mazefsky et al.1 rigorously extend the Emotion Dysregulation Inventory (EDI; a set of questionnaires) to 2 groups of preschoolers, those representing children with neurodevelopmental issues, especially autism, and those without.

Can peripheral psychophysiological markers predict response to exposure-based cognitive behavioral therapy in youth with severely impairing irritability? A study protocol.

BACKGROUND: Irritability, an increased proneness to anger, is a primary reason youth present for psychiatric care. While initial evidence supports the efficacy of exposure-based cognitive behavioral therapy (CBT) for youth with clinically impairing irritability, treatment mechanisms remain unclear. Here, we propose to measure peripheral psychophysiological indicators of arousal-heart rate (HR)/electrodermal activity (EDA)-and regulation-heart rate variability (HRV)-during exposures to anger-inducing stimuli as potential predictors of treatment efficacy. The objective of this study is to evaluate whether in-situ biosensing data provides peripheral physiological indicators of in-session response to exposures. METHODS: Blood volume pulse (BVP; from which HR and HRV canl be derived) and EDA will be collected ambulatorily using the Empatica EmbracePlus from 40 youth (all genders; ages 8-17) undergoing six in-person exposure treatment sessions, as part of a multiple-baseline trial of exposure-based CBT for clinically impairing irritability. Clinical ratings of irritability will be conducted at baseline, weekly throughout treatment, and at 3-month and 6-month follow-ups via the Clinical Global Impressions Scale (CGI) and the Affective Reactivity Index (ARI; clinician-, parent-, and child-report). Multilevel modeling will be used to assess within- and between-person changes in physiological arousal and regulation throughout exposure-based CBT and to determine whether individual differences are predictive of treatment response. DISCUSSION: This study protocol leverages a wearable biosensor (Empatica) to continuously record HR/HRV (derived from BVP) and EDA during in-person exposure sessions for youth with clinically impairing irritability. Here, the goal is to identify changes in physiological arousal (EDA, HR) and regulation (HRV) over the course of treatment in tandem with changes in clinical symptoms. TRIAL REGISTRATION: The participants in this study come from an overarching clinical trial (trial registration numbers: NCT02531893 first registered on 8/25/2015; last updated on 8/25/2023). The research project and all related materials were submitted and approved by the appropriate Institutional Review Board of the National Institute of Mental Health (NIMH).

An Introduction to Generative Artificial Intelligence in Mental Health Care: Considerations and Guidance.

PURPOSE OF REVIEW: This paper provides an overview of generative artificial intelligence (AI) and the possible implications in the delivery of mental health care. RECENT FINDINGS: Generative AI is a powerful technology that is changing rapidly. As psychiatrists, it is important for us to understand generative AI technology and how it may impact our patients and our practice of medicine. This paper aims to build this understanding by focusing on GPT-4 and its potential impact on mental health care delivery. We first introduce key concepts and terminology describing how the technology works and various novel uses of it. We then dive into key considerations for GPT-4 and other large language models (LLMs) and wrap up with suggested future directions and initial guidance to the field.

The Coronavirus Impact Scale: Construction, Validation, and Comparisons in Diverse Clinical Samples.

Objective: This report is of the construction and initial psychometric properties of the Coronavirus Impact Scale in multiple large and diverse samples of families with children and adolescents. The scale was established to capture the impact of the coronavirus pandemic during its first wave. Differences in impact between samples and internal structure within samples were assessed. Method: A total of 572 caregivers of children and adolescents or expecting mothers in diverse clinical and research settings completed the Coronavirus Impact Scale. Samples differed in regard to developmental stage, background, inpatient/outpatient status, and primary research or clinical setting. Model free methods were used to measure the scale's internal structure and to determine a scoring method. Differences between samples in specific item responses were measured by multivariate ordinal regression. Results: The Coronavirus Impact Scale demonstrated good internal consistency in a variety of clinical and research populations. Across the groups studied, single, immigrant, predominantly Latinx mothers of young children reported the greatest impact of the pandemic, with noteworthy effects on food access and finances reported. Individuals receiving outpatient or inpatient care reported greater impacts on health care access. Elevated scores on the Coronavirus Impact Scale were positively associated with measures of caregiver anxiety and both caregiver- and child-reported stress at a moderate effect size. Conclusion: The Coronavirus Impact Scale is a publicly available scale with adequate psychometric properties for use in measuring the impact of the coronavirus pandemic in diverse populations.

A Computational Model Reveals Learning Dynamics During Interpretation Bias Training With Clinical Applications.

BACKGROUND: Some psychopathologies, including anxiety and irritability, are associated with biases when judging ambiguous social stimuli. Interventions targeting these biases, or interpretation bias training (IBT), are amenable to computational modeling to describe their associative learning mechanisms. Here, we translated ALCOVE (attention learning covering map), a model of category learning, to describe learning in youths with affective psychopathology when training on more positive judgments of ambiguous face emotions. METHODS: A predominantly clinical sample comprised 71 youths (age range, 8-22 years) representing broad distributions of irritability and anxiety symptoms. Of these, 63 youths were included in the test sample by completing an IBT task with acceptable performance for computational modeling. We used a separate sample of 28 youths to translate ALCOVE for individual estimates of learning rate and generalization. In the test sample, we assessed associations between model learning estimates and irritability, anxiety, their shared variance (negative affectivity), and age. RESULTS: Age and affective symptoms were associated with category learning during IBT. Lower learning rates were associated with higher negative affectivity common in anxiety and irritability. Lower generalization, or improved discrimination between face emotions, was associated with increasing age. CONCLUSIONS: This work demonstrates a functional consequence of age- and symptom-related learning during interpretation bias. Learning measured by ALCOVE also revealed learning types not accounted for in the prior literature on IBT. This work more broadly demonstrates the utility of measurement models for understanding trial-by-trial processes and identifying individual learning styles.

Editorial: The Neural Systems of Fairness, Retaliation, and Aggression.

"Not fair!" is a call to action regularly heard by parents and mental health professionals. It is well known that a person's perception of fairness might provoke them to anger and aggression.1 Beyond common experience, all sorts of experiments involving people's responses to rigged, interactive games have proved the point. Indeed, it is not just people; de Waal2 charmed the world with a TED talk in which monkeys took umbrage and aggressed in response to unfairness. Knowing this, Mathur et al.3 used unfairness and retaliation to illuminate the complex neural circuity of aggression in adolescents.

Finding a Needed Diagnostic Home for Children with Impulsive Aggression.

Aggressive behavior is one of the most common reasons for referrals of youth to mental health treatment. While there are multiple publications describing different types of aggression in children, it remains challenging for clinicians to diagnose and treat aggressive youth, especially those with impulsively aggressive behaviors. The reason for this dilemma is that currently several psychiatric diagnoses include only some of the common symptoms of aggression in their criteria. However, no single diagnosis or diagnostic specifier adequately captures youth with impulsive aggression (IA). Here we review select current diagnostic categories, including behavior and mood disorders, and suggest that they do not provide an adequate description of youth with IA. We also specifically focus on the construct of IA as a distinct entity from other diagnoses and propose a set of initial, provisional diagnostic criteria based on the available evidence that describes youth with IA to use for future evaluation.

Adverse childhood experiences and hormonal contraception: Interactive impact on sexual reward function.

The current literature suggests that some women are uniquely vulnerable to negative effects of hormonal contraception (HC) on affective processes. However, little data exists as to which factors contribute to such vulnerability. The present study evaluated the impact of prepubertal adverse childhood experiences (ACEs) on reward processing in women taking HC (N = 541) compared to naturally cycling women (N = 488). Participants completed an online survey assessing current and past HC use and exposure to 10 different adverse childhood experiences (ACEs) before puberty (ACE Questionnaire), with participants categorized into groups of low (0-1) versus high (≥2) prepubertal ACE exposure. Participants then completed a reward task rating their expected and experienced valence for images that were either erotic, pleasant (non-erotic), or neutral. Significant interactions emerged between prepubertal ACE exposure and HC use on expected (p = 0.028) and experienced (p = 0.025) valence ratings of erotic images but not pleasant or neutral images. Importantly, follow-up analyses considering whether women experienced HC-induced decreases in sexual desire informed the significant interaction for expected valence ratings of erotic images. For current HC users, prepubertal ACEs interacted with HC-induced decreased sexual desire (p = 0.008), such that high ACE women reporting decreased sexual desire on HC showed substantially decreased ratings for anticipated erotic images compared to both high prepubertal ACE women without decreased sexual desire (p < 0.001) and low prepubertal ACE women also reporting decreased sexual desire (p = 0.010). The interaction was not significant in naturally cycling women reporting previous HC use, suggesting that current HC use could be impacting anticipatory reward processing of sexual stimuli among certain women (e.g., high prepubertal ACE women reporting HC-induced decreases in sexual desire). The study provides rationale for future randomized, controlled trials to account for prepubertal ACE exposure to promote contraceptive selection informed by behavioral evidence.

Trait anxiety is associated with amygdala expectation and caloric taste receipt response across eating disorders.

Anxious traits are elevated in eating disorders (EDs), are considered risk factors for ED development, and trait anxiety has been linked to ED psychopathology. How trait anxiety relates to ED neurobiology is not well understood. In this study 197 individuals across the ED spectrum (anorexia nervosa n = 91; other specified EDs n = 34; bulimia nervosa n = 56; binge ED n = 16), and 120 healthy controls were assessed for anxious traits and learned to expect and receive caloric or neutral taste stimuli during brain imaging. Amygdala sucrose expectation response differed across groups (Wilk's lambda = 0.945, p = 0.023), and was higher on the left in anorexia nervosa compared to healthy controls (p = 0.002). Expected sucrose receipt response across taste reward regions was not different between groups. In the ED sample, trait anxiety negatively moderated the relationship between amygdala expectation and right dorsal (p = 0.0062) and ventral (p = 0.0046) anterior insula receipt response. A subgroup analysis showed similar results for anorexia nervosa, and partially in bulimia nervosa. Across EDs, appetitive motivation correlated positively with bilateral orbitofrontal cortex, caudate head, and ventral striatal sucrose receipt response (r = 0.215 to 0.179, p = 0.002 to 0.012). Across the study sample, trait anxiety showed an inverted-U-shaped relationship with right (r = 0.147, p = 0.034) and left (r = 0.162, p = 0.016) amygdala expectation response. Amygdala sucrose expectation response is elevated in anorexia nervosa, correlates with sucrose receipt response, and this relationship is negatively moderated by trait anxiety across EDs. Trait anxiety may have an important role in how expectation drives taste stimulus receipt brain response and perhaps food approach in individuals with EDs.

Brain reward response in adolescents and young adults with anorexia nervosa is moderated by changes in body weight and sweetness perception.

OBJECTIVE: Anorexia nervosa (AN) is a severe psychiatric illness with complex etiology. Recently, we found elevated striatal brain response to sweet taste stimuli in adolescents and young adults with AN. Here, we tested the hypothesis that nutritional rehabilitation normalizes prediction error activation, a measure for dopamine-related reward circuit response, to salient caloric taste stimuli in AN. METHODS: A total of 28 individuals with AN (age = 16 ± 2 years; body mass index [BMI] = 16 ± 1) who previously underwent brain imaging while performing a taste prediction error task using sucrose as salient caloric stimulus, participated in a second brain imaging scan (BMI = 18 ± 1) after intensive specialized eating disorder treatment (41 ± 15 days). A total of 31 healthy controls (age = 16 ± 3 years; BMI = 21 ± 2) were also studied on two occasions. RESULTS: At baseline, individuals with AN demonstrated an elevated salience response in bilateral caudate head and nucleus accumbens, and right ventral striatum. At the second scan, elevated response was only found in the right nucleus accumbens. A moderator analysis indicated that greater increase in BMI and greater decrease in sweetness perception predicted lesser prediction error response at the second scan in AN. CONCLUSION: Consistent with the previously reported monetary stimulus-response, elevated taste prediction error response in AN was largely absent after weight restoration. This study indicates that changes in BMI and sweet taste perception are independent moderators of change of brain salience response in adolescents and young adults with AN. The study points toward dynamic changes in the brain reward circuitry in AN and highlights the importance of nutrition and weight restoration in that process. PUBLIC SIGNIFICANCE STATEMENT: AN is a severe psychiatric illness. Biological factors that integrate neurobiology and behavior could become important targets to improve treatment outcome. This study highlights the importance of weight normalization and taste perception the normalization of brain function, and food type or taste-specific interventions could help in the recovery process. Furthermore, the study suggests that food-related and nonfood-related reward processing adapts to illness state in AN.

Changes in Internalizing Symptoms During the COVID-19 Pandemic in a Transdiagnostic Sample of Youth: Exploring Mediators and Predictors.

The COVID-19 pandemic is a chronically stressful event, particularly for youth. Here, we examine (i) changes in mood and anxiety symtpoms, (ii) pandemic-related stress as a mediator of change in symptoms, and (ii) threat processing biases as a predictor of increased anxiety during the pandemic. A clinically well-characterized sample of 81 youth ages 8-18 years (M = 13.8 years, SD = 2.65; 40.7% female) including youth with affective and/or behavioral psychiatric diagnoses and youth without psychopathology completed pre- and during pandemic assessments of anxiety and depression and COVID-related stress. Forty-six youth also completed a threat processing fMRI task pre-pandemic. Anxiety and depression significantly increased during the pandemic (all ps < 0.05). Significant symptom change was partially mediated by pandemic stress and worries. Increased prefrontal activity in response to neutral faces pre-pandemic was associated with more intense parent-reported anxiety during the pandemic (all Fs(1.95,81.86) > 14.44, ps < 0.001). The present work extends existing knowledge on the mediating role of psychological stress on symptoms of anxiety and depression in youth.

Context-dependent amygdala-prefrontal connectivity during the dot-probe task varies by irritability and attention bias to angry faces.

Irritability, defined as proneness to anger, is among the most common reasons youth are seen for psychiatric care. Youth with irritability demonstrate aberrant processing of anger-related stimuli; however, the neural mechanisms remain unknown. We applied a drift-diffusion model (DDM), a computational tool, to derive a latent behavioral metric of attentional bias to angry faces in youth with varying levels of irritability during functional magnetic resonance imaging (fMRI). We examined associations among irritability, task behavior using a DDM-based index for preferential allocation of attention to angry faces (i.e., extra-decisional time bias; Δt0), and amygdala context-dependent connectivity during the dot-probe task. Our transdiagnostic sample, enriched for irritability, included 351 youth (ages 8-18; M = 12.92 years, 51% male, with primary diagnoses of either attention deficit/hyperactivity disorder [ADHD], disruptive mood dysregulation disorder [DMDD], an anxiety disorder, or healthy controls). Models accounted for age, sex, in-scanner motion, and co-occurring symptoms of anxiety. Youth and parents rated youth's irritability using the Affective Reactivity Index. An fMRI dot-probe task was used to assess attention orienting to angry faces. In the angry-incongruent vs. angry-congruent contrast, amygdala connectivity with the bilateral inferior frontal gyrus (IFG), insula, caudate, and thalamus/pulvinar was modulated by irritability level and attention bias to angry faces, Δt0, all ts350 > 4.46, ps < 0.001. In youth with high irritability, elevated Δt0 was associated with a weaker amygdala connectivity. In contrast, in youth with low irritability, elevated Δt0 was associated with stronger connectivity in those regions. No main effect emerged for irritability. As irritability is associated with reactive aggression, these results suggest a potential neural regulatory deficit in irritable youth who have elevated attention bias to angry cues.

Reliability of task-evoked neural activation during face-emotion paradigms: Effects of scanner and psychological processes.

Assessing and improving test-retest reliability is critical to efforts to address concerns about replicability of task-based functional magnetic resonance imaging. The current study uses two statistical approaches to examine how scanner and task-related factors influence reliability of neural response to face-emotion viewing. Forty healthy adult participants completed two face-emotion paradigms at up to three scanning sessions across two scanners of the same build over approximately 2 months. We examined reliability across the main task contrasts using Bayesian linear mixed-effects models performed voxel-wise across the brain. We also used a novel Bayesian hierarchical model across a predefined whole-brain parcellation scheme and subcortical anatomical regions. Scanner differences accounted for minimal variance in temporal signal-to-noise ratio and task contrast maps. Regions activated during task at the group level showed higher reliability relative to regions not activated significantly at the group level. Greater reliability was found for contrasts involving conditions with clearly distinct visual stimuli and associated cognitive demands (e.g., face vs. nonface discrimination) compared to conditions with more similar demands (e.g., angry vs. happy face discrimination). Voxel-wise reliability estimates tended to be higher than those based on predefined anatomical regions. This work informs attempts to improve reliability in the context of task activation patterns and specific task contrasts. Our study provides a new method to estimate reliability across a large number of regions of interest and can inform researchers' selection of task conditions and analytic contrasts.

The Neural Circuitry of Reward During Sustained Threat.

Reward processing is important for understanding behavior in psychopathology. Opportunities to earn money activate the ventral striatum, as shown by the monetary incentive delay (MID) task. Anxiety conditions have been modeled by presenting shocks and startling sounds. To further investigate the co-occurrence of an anxiety condition and a rewarding stimulus, we modified the MID to include a sustained threat of scream. This study investigated neural patterns of the MID task with an uncertain threat of a startling scream. Forty-three young adults completed a functional MRI scan. The task included two conditions (scream and safe) and three cues (gain $5, gain $0, lose $5). Analyses included a whole brain, group analysis using a linear mixed-effects model and a paired t-test. The whole brain analysis revealed a main effect of cue, with increased ventral striatal activation (F2,210 = 58.8, p < 0.001) during cues to gain or lose $5. We observed a main effect of condition during cue presentation, such that bilateral insula and putamen activation was diminished (p < 0.001) in the scream versus the safe condition. A t-test of condition showed increased activation during threat blocks in the insula and putamen. A time course graph revealed that activation in the insula and putamen responded similarly to incentive but had an overall elevation during the scream condition. These results replicated expected activation in reward and in the setting of uncertain threat. Our results show that uncertain threat increases the magnitude of activation in the dorsal striatum.

Understanding Irritability in Relation to Anger, Aggression, and Informant in a Pediatric Clinical Population.

OBJECTIVE: Despite its clinical relevance to pediatric mental health, the relationship of irritability with anger and aggression remains unclear. We aimed to quantify the relationships between well-validated, commonly used measurements of these constructs and informant effects in a clinically relevant population. METHOD: A total of 195 children with primary diagnoses of attention-deficit/hyperactivity disorder, disruptive mood dysregulation disorder, or no major disorder and their parents rate irritability, anger, and aggression on measures of each construct. Construct and informant relationships were mapped via multi-trait, multi-method factor analysis. RESULTS: Parent- and child-reported irritability and child-reported anger are highly associated (r = 0.89) but have some significant differences. Irritability overlaps with outward expression of anger but diverges from anger in anger suppression and control. Aggression has weaker associations with both irritability (r = 0.56) and anger (r = 0.49). Across measures, informant source explains a substantial portion of response variance. CONCLUSION: Irritability, albeit distinct from aggression, is highly associated with anger, with notable overlap in child-reported outward expression of anger, providing empirical support for formulations of clinical irritability as a proneness to express anger outwardly. Diagnostic and clinical intervention work on this facet of anger can likely translate to irritability. Further research on external validation of divergence of these constructs in anger suppression and control may guide future scale revisions. The proportion of response variance attributable to informant may be an under-recognized confound in clinical research and construct measurement.

A Randomized Controlled Trial of Computerized Interpretation Bias Training for Disruptive Mood Dysregulation Disorder: A Fast-Fail Study.

OBJECTIVE: To examine targeted, mechanism-based interventions is the next generation of treatment innovation. Biased threat labeling of ambiguous face emotions (interpretation bias) is a potential behavioral treatment target for anger, aggression, and irritability. Changing biases in face-emotion labeling may improve irritability-related outcomes. Here, we report the first randomized, double-blind, placebo-controlled targeted trial of interpretation bias training (IBT) in youths with chronic, severe irritability. METHOD: Patients with current disruptive mood dysregulation disorder (DMDD; N = 44) were randomly assigned to complete 4 sessions of active (n = 22) or sham (n = 22) computerized IBT training within a 1-week period. The first and last trainings were completed onsite, and 2 trainings were completed at home. We examined the effects of active IBT on labeling bias, primary outcome measures of irritability, and secondary outcome measures of anxiety, depression, and functional impairment. Follow-up assessments were completed immediately after the intervention as well as 1 and 2 weeks later. RESULTS: We found that active IBT engaged the behavioral target in the active relative to the sham condition, as shown by a significant shift toward labeling ambiguous faces as happy. However, there was no consistent clinical improvement in active IBT relative to the sham condition either immediately after or 2 weeks after training in either the primary or secondary outcome measures. CONCLUSION: Although this randomized controlled trial of IBT in youths with DMDD engaged the proposed behavioral target, there was no statistically significant improvement on clinical outcome. Identifying and changing behavioral targets is a first step in novel treatment development; these results have broader implications for target-based intervention development. CLINICAL TRIAL REGISTRATION INFORMATION: Psychological Treatments for Youth With Severe Irritability; https://clinicaltrials.gov/; NCT02531893.

Explaining the Return of Fear with Revised Rescorla-Wagner Models.

Exposure therapy - exposure to a feared stimulus without harmful consequences - can reduce fear responses in many mental disorders. However, such relief is often partial and temporary: fear can return after the therapy has ended. Conditioning research has identified three mechanisms for the return of fear, viz. change in physical context (renewal), the passage of time (spontaneous recovery), and an encounter with the fear-producing unconditioned stimulus (reinstatement). To understand why fear returns and thereby develop more effective therapies, we develop mathematical learning models based on that of Rescorla and Wagner. According to this model, context cues present during extinction become conditioned inhibitors (i.e. safety signals) which prevent total erasure of the threat association. Adding various mechanisms to the model allows it to explain different facets of the return of fear. Among these mechanisms is decay of inhibitory associations, which provides a novel explanation for spontaneous recovery. To make the benefits of exposure robust and permanent, one must minimize the degree to which the extinction context becomes inhibitory in order to maximize unlearning. We simulate several experimental paradigms that reduce the return of fear and explain them according to this principle.