Fear attenuation collaborations to optimize translation.

Here, we describe the efforts we dedicated to the challenge of modifying entrenched emotionally laden memories. In recent years, through a number of collaborations and using a combination of behavioral, molecular, and computational approaches, we: (a) developed novel approaches to fear attenuation that engage mechanisms that differ from those engaged during extinction (Monfils), (b) examined whether our approaches can generalize to other reinforcers (Lee, Gonzales, Chaudhri, Cofresi, and Monfils), (c) derived principled explanations for the differential outcomes of our approaches (Niv, Gershman, Song, and Monfils), (d) developed better assessment metrics to evaluate outcome success (Shumake and Monfils), (e) identified biomarkers that can explain significant variance in our outcomes of interest (Shumake and Monfils), and (f) developed better basic research assays and translated efforts to the clinic (Smits, Telch, Otto, Shumake, and Monfils). We briefly highlight each of these milestones and conclude with final remarks and extracted principles. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Improving Exposure Therapy: Rationale and Design of an International Consortium.

The Exposure Therapy Consortium (ETC) was established to advance the science and practice of exposure therapy. To encourage participation from researchers and clinicians, this article describes the organizational structure and activities of the ETC. Initial research working group experiences and a proof-of-principle study underscore the potential of team science and larger-scale collaborative research in this area. Clinical working groups have begun to identify opportunities to enhance access to helpful resources for implementing exposure therapy effectively. This article discusses directions for expanding the consortium's activities and its impact on a global scale.

Isradipine augmentation of virtual reality cue exposure therapy for tobacco craving: a triple-blind randomized controlled trial.

Preclinical research with rodents suggests that the L-type calcium channel blocker isradipine can enhance long-term extinction of conditioned place preference for addictive substances when it is administered in conjunction with extinction training. Although isradipine alone, which is FDA-approved for hypertension, has not shown a direct effect on craving in human drug users, its potential to augment behavioral treatments designed to reduce craving remains unknown. We conducted a triple-blind, randomized placebo-controlled pilot clinical trial of isradipine combined with a novel virtual reality cue exposure therapy (VR-CET) approach with multimodal cues that targeted craving. After 24 hours of abstinence, 78 adults with an ongoing history of daily cigarette use received isradipine (n = 40) or placebo (n = 38) and reported craving levels after each of 10 trials of VR-CET. Consistent with pre-registered hypotheses, the isradipine group had significantly lower mean craving across cue exposure trials at the medication-free 24-hour follow-up (d = -0.42, p = 0.046). There were no serious adverse events; however, side effects such as headache and dizziness occurred more frequently in the isradipine group. The findings of the current study support follow-up clinical trials that specifically test the efficacy of isradipine-augmented VR-CET for reducing smoking relapse rates after an initial quit attempt. clinicaltrials.gov: NCT03083353.

The Role of Functional Health Literacy in terms of Harmful Alcohol Use in Adults with Probable Posttraumatic Stress Disorder and Alcohol Use Disorder.

Purpose: The current study examined functional health literacy (FHL) in regard to hazardous drinking among a sample with probable posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Methods: Participants were 565 adults with probable PTSD and hazardous alcohol use (52.2% female, 68.8% Non-Hispanic White, average age = 39.2 years ± 10.9 years). Results: FHL literacy maintained statistically significant role in terms of hazardous drinking (p < .001) even in the context of posttraumatic stress. Conclusion: FHL may be important to better understand hazardous drinking among persons with comorbid PTSD and AUD.

Carbon Dioxide Reactivity Differentially Predicts Fear Expression After Extinction and Retrieval-Extinction in Rats.

Background: Cues present during a traumatic event may result in persistent fear responses. These responses can be attenuated through extinction learning, a core component of exposure therapy. Exposure/extinction is effective for some people, but not all. We recently demonstrated that carbon dioxide (CO2) reactivity predicts fear extinction memory and orexin activation and that orexin activation predicts fear extinction memory, which suggests that a CO2 challenge may enable identification of whether an individual is a good candidate for an extinction-based approach. Another method to attenuate conditioned responses, retrieval-extinction, renders the original associative memory labile via distinct neural mechanisms. The purpose of the current study was to examine whether we could replicate previous findings that retrieval-extinction is more effective than extinction at preventing the return of fear and that CO2 reactivity predicts fear memory after extinction. We also examined whether CO2 reactivity predicts fear memory after retrieval-extinction. Methods: Male rats first underwent a CO2 challenge and fear conditioning and were assigned to receive either standard extinction (n = 28) or retrieval-extinction (n = 28). Then, they underwent a long-term memory (LTM) test and a reinstatement test. Results: We found that retrieval-extinction resulted in lower freezing during extinction, LTM, and reinstatement than standard extinction. Using the best subset approach to linear regression, we found that CO2 reactivity predicted LTM after extinction and also predicted LTM after retrieval-extinction, although to a lesser degree. Conclusions: CO2 reactivity could be used as a screening tool to determine whether an individual may be a good candidate for an extinction-based therapeutic approach.

Extinction learning underlies exposure therapy, a treatment for anxiety disorders. However, not everyone benefits from exposure therapy, highlighting the need in developing approaches that may help predict which individuals will respond. We tested whether extinction or an alternative treatment called retrieval-extinction would be more effective at reducing conditioned fear responses in rats and whether the response to a carbon dioxide (CO₂) challenge would predict treatment response. We found that retrieval-extinction was more effective at reducing fear, and CO₂ reactivity was better at predicting the response to extinction. These findings could help improve treatment strategies for anxiety disorders.

Efficacy and implementation of exercise-based smoking cessation treatment for adults with high anxiety sensitivity (STEP): Study protocol for a randomized controlled trial.

Anxiety sensitivity (AS), reflecting the fear of bodily sensations, is a transdiagnostic vulnerability factor that underpins both affective psychopathology and smoking. Phase II research supports the efficacy of a 15-week community-based intervention (STEP) that combines high-intensity exercise offered by the YMCA with standard smoking cessation treatment (tobacco quitline and nicotine replacement therapy) for sedentary smokers with elevated AS. This Phase III study aims to enroll 360 adults to evaluate whether STEP efficacy for achieving smoking abstinence generalizes to Black and Hispanic smokers with elevated AS.

Negative emotional reactivity to minority stress: measure development and testing.

The purpose of the present investigation was to develop and test a measure of negative emotional reactivity to racial/ethnic minoritized stress. In Study 1, we developed item content for a measure of negative emotional reactivity to racial/ethnic minoritized stress. We then evaluated item performance and produced a refined 15-item scale among a large sample of racial/ethnic minority adults (N = 1,343). Results supported a unidimensional construct and high levels of internal consistency. The factor structure and internal consistency were replicated and extended to a sample of Latinx persons who smoke (N = 338) in Study 2. There was evidence of convergent validity of the Emotional Reactivity to Minoritized Stress (ERMS) total score in terms of theoretically consistent and statistically significant relations with indices of mental health problems, social determinants of health, and substance use processes. There was also evidence that the ERMS demonstrated divergent validity in that it was negatively associated with psychological well-being, health literacy, subjective social status in Study 1, and positive abstinence expectancies in Study 2. Overall, the present study establishes the reliability and validity of measuring individual differences in negative emotional reactivity to racial/ethnic minority stress with the ERMS and that such responsivity is associated with behavioral health problems.

Caveat emptor: Mental health specialty certifications and the public's preferences for clinical care.

Appropriate training and continuing education for mental health professionals are designed to ensure that clinicians provide effective and ethical care. Mental health consumers may depend upon these credentials to judge the level of a professional's competence, but whether these activities and credentials provide a valid indicator of knowledge and skills is subject to debate. The present study was designed to examine preferences for mental health clinicians among potential consumers and factors that may inform these preferences, specifically comparing preferences for doctoral-level mental health clinicians and masters-level clinicians with and without specialty certification for treating anxiety symptoms. Cross-sectional assessment with self-report surveys (clinician preferences, prior mental health diagnosis and treatment, demographic characteristics, generalized anxiety symptoms, mental health literacy, and mental health stigma) was administered in two samples: a college student sample (N = 224; 71.9% female; Mage = 19.1, SD = 1.5) and a sample of adults with chronic pain (N = 116; 74.1% female; Mage = 43.8, SD = 13.8). The present study found that across both samples, therapists with a specialty certification were preferred over those without such credentials within each profession, and that certification status trumped professional standing such that certified masters-level clinicians were rated more highly than noncertified PhD-level clinicians. These findings are indicative of a schism between how the field of clinical psychology conceptualizes itself and how it is seen by its consumers. Implications of our findings for mental health consumers, clinicians, and professional organizations are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

On the importance of identifying mechanisms and active ingredients of psychological treatments.

This commentary addresses the thought-provoking article by Lorenzo-Luaces (in press). We review areas of both agreement and disagreement with the author's points, noting that readers should not infer that research into active ingredients and mechanisms is pointless. We conclude with a call for more research into the mechanisms of therapeutic change and the active ingredients of therapeutic interventions, with the aim of disseminating treatments that are both effective and efficient.

What good are positive emotions for treatment? A replication test of whether trait positive emotionality predicts response to exposure therapy for social anxiety disorder.

BACKGROUND: Positive valence emotions serve functions that may facilitate response to exposure therapy - they encourage approach behavior, diminish perceived threat reactivity, and enhance assimilation of new information in memory. Few studies have examined whether positive emotions predict exposure therapy success and extant findings are mixed. METHODS: We conducted a secondary analysis of an exposure therapy trial for social anxiety disorder to test the hypothesis that patients endorsing higher trait positive emotions at baseline would display the greatest treatment response. N = 152 participants enrolled in a randomized controlled trial of d-cycloserine augmentation completed five sessions of group exposure therapy. Pre-treatment positive emotionality was assessed using the NEO Five-Factor Inventory. Social anxiety symptoms were assessed throughout treatment by blinded evaluators using the Liebowitz Social Anxiety Scale. RESULTS: Accounting for baseline symptom severity, multilevel growth curve models revealed that patients with higher pre-treatment positive emotionality displayed faster social anxiety symptom reductions and lower scores at 3-month follow-up. This predictive effect remained significant after controlling for baseline depression and extraversion (without the positive emotionality facet). CONCLUSIONS: These findings add to emerging evidence suggesting that explicitly targeting and enhancing positive emotions during exposure to perceived threat may improve treatment outcomes for anxiety and fear-based disorders. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02066792https://clinicaltrials.gov/ct2/show/NCT02066792.

Augmenting the efficacy of benzodiazepine taper with telehealth-delivered cognitive behavioral therapy for anxiety disorders in patients using prescription opioids: A pilot randomized controlled trial.

The risks of concomitant benzodiazepine (BZ) and opioid use are significant. Despite the urgent need to reduce BZ use among patients taking opioids, no treatment intervention research to our knowledge has addressed treatment for this concurrent, high-risk use. The current study will evaluate the efficacy of augmenting BZ taper procedures with CBT for anxiety disorders that has been adapted specifically for patients with concomitant BZ and opioid use (either use as prescribed or misuse), a high-risk patient population. Research combining rapidly scalable behavioral interventions ancillary to pharmacological approaches delivered via telehealth in primary care settings is innovative and important given concerning trends in rising prevalence of BZ/opioid co-prescription, BZ-associated overdose deaths, and known barriers to implementation of behavioral health interventions in primary care. CBT delivery using telehealth has the potential to aid adherence and promote access and dissemination of procedures in primary care. Lastly, the current study will utilize an experimental therapeutics approach to preliminarily explore the mechanism of action for the proposed interventions. The overall aim of the present pilot randomized controlled trial is to examine the feasibility and preliminary efficacy of a BZ taper with CBT for anxiety disorders adapted for patients with concomitant BZ (BZT + CBT) and opioid use to a BZ taper with a control health education program (BZT + HE) in a sample of individuals (N = 54) who have been prescribed and are taking benzodiazepines and opioids for at least 3 months prior to baseline and experience anxious distress. Screening and outcome measures, methods, and implications are described. Trial Registration: ClinicalTrials.gov (NCT05573906).

Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of exposure-based CBT.

BACKGROUND: Over a decade and a half of research has resulted in inconsistent evidence for the efficacy of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, for augmenting exposure-based cognitive behavioral therapy (CBT) for anxiety- and fear-based disorders. These variable findings have motivated the search for moderators of DCS augmentation efficacy. METHODS: In this secondary analysis of a previous randomized clinical trial, we evaluated the value of de novo threat conditioning outcomes-degree of threat acquisition, extinction, and extinction retention-for predicting treatment response to exposure-based CBT for social anxiety disorder, applied with and without DCS augmentation in a sample of 59 outpatients. RESULTS: We found that average differential skin conductance response (SCR) during extinction and extinction retention significantly moderated the prediction of clinical response to DCS: participants with poorer extinction and extinction retention showed relatively improved treatment response with DCS. No such effects were found for expectancy ratings, consistent with accounts of DCS selectively aiding lower-order but not higher-order extinction learning. CONCLUSIONS: These findings provide support for extinction and extinction retention outcomes from threat conditioning as potential pre-treatment biomarkers for DCS augmentation benefits. Independent of DCS augmentation, the current study did not support threat conditioning outcomes as useful for predicting response to exposure-based CBT.

An Experimental Therapeutics Focus on Novel Mechanistic Targets in Cognitive Behavioral Treatments: Introduction to the Special Section.

This article introduces the special section, "An Experimental Therapeutics Focus on Novel Mechanistic Targets in Cognitive Behavioral Treatments." The purpose of this special section is to highlight research that follows the recommended Science of Behavior Change (SOBC) developmental progression for an experimental medicine approach to identifying and testing mechanisms of behavior change. Emphasis was placed on the earlier stage "pipeline" of investigations of novel mechanisms for behavior change: mechanisms that are undergoing the initial stages of validation. In this series, seven empirical articles are presented and are followed by an article detailing a checklist for reporting mechanistic research studies in order to improve communication of findings in the field. The final article in this series discusses the history, current status, and future directions for the SOBC approach to mechanistic science as viewed by National Institute of Health program officials.

Improving the Rigor of Mechanistic Behavioral Science: The Introduction of the Checklist for Investigating Mechanisms in Behavior-Change Research (CLIMBR).

Diverse fields rely on the development of effective interventions to change human behaviors, such as following prescribed medical regimens, engaging in recommended levels of physical activity, getting vaccinations that promote individual and public health, and getting a healthy amount of sleep. Despite recent advancements in behavioral intervention development and behavior-change science, systematic progress is stalled by the lack of a systematic approach to identifying and targeting mechanisms of action that underlie successful behavior change. Further progress in behavioral intervention science requires that mechanisms be universally prespecified, measurable, and malleable. We developed the CheckList for Investigating Mechanisms in Behavior-change Research (CLIMBR) to guide basic and applied researchers in the planning and reporting of manipulations and interventions relevant to understanding the underlying active ingredients that do-or do not-drive successful change in behavioral outcomes. We report the rationale for creating CLIMBR and detail the processes of its development and refinement based on feedback from behavior-change experts and NIH officials. The final version of CLIMBR is included in full.

Why now and not later? An exploration into the neurocognitive correlates of delay discounting in bipolar disorder.

Increased delay discounting is evident in bipolar disorder, though there is minimal research on the factors that impact delay discounting in this population. We evaluated neurocognitive correlates of delay discounting among relatively euthymic participants with bipolar disorder (N = 76) with (n = 31) and without (n = 45) past-year substance use disorders. There were no significant differences in the mean delay discounting value between the bipolar disorder group and the comorbid bipolar disorder and past-year substance use disorders group (p = .082, Cohen's d = 0.41). Using multiple regression, we evaluated the most important predictors of the delay discounting value. Impairments in executive functioning (per number of categories completed on the Wisconsin Card Sorting Test) and visuospatial construction (per the Rey-Osterrieth Complex Figure Test Copy Raw Score), as well as decreased years of education (all ps < .05), offered the best neurocognitive characterization of increased delay discounting in this sample.

CO2 reactivity is associated with individual differences in appetitive extinction memory.

Pavlovian conditioning can underly the maladaptive behaviors seen in psychiatric disorders such as anxiety and addiction. In both the lab and the clinic, these responses can be attenuated through extinction learning, but often return with the passage of time, stress, or a change in context. Extinction to fear and reward cues are both subject to these return of behavior phenomena and have overlap in neurocircuitry, yet it is unknown whether they share any common predictors. The orexin system has been implicated in both fear and appetitive extinction and can be activated through a CO2 challenge. We previously found that behavioral CO2 reactivity predicts fear extinction and orexin activation. Here, we sought to extend our previous findings to determine whether CO2 reactivity might also predict extinction memory for appetitive light-food conditioning. We find that the same subcomponent of behavioral CO2 reactivity that predicted fear extinction also predicts appetitive extinction, but in the opposite direction. We show evidence that this subcomponent remains stable across two CO2 challenges, suggesting it may be a stable trait of both behavioral CO2 reactivity and appetitive extinction phenotype. Our findings further the possibility for CO2 reactivity to be used as a transdiagnostic screening tool to determine whether an individual would be a good candidate for exposure therapy.

Climate change views examined through a behavioral medicine frame: are there potential target mechanisms for change beyond political ideology?

The threat of climate change is associated with both profound health consequences and failures by many individuals to take preventive actions. Behavioral science research on health behavior engagement may serve as a lens through which to better understand attitudes associated with the threat of climate change. This study was designed to examine individual differences in attitudinal responses to climate change, understanding the degree to which these responses can be predicted by both political beliefs and more readily modified psychological factors commonly associated with health behavior engagement: locus of control, anxiety sensitivity, delay discounting, and intolerance of uncertainty. Participants (N = 234) were US adults (62% male; 57% Non-Hispanic White; 44% Democrat) who completed an online survey. Stepwise multiple linear regressions examined which variables provided non-redundant prediction in models of climate change beliefs and concerns. In addition to providing support for the role of political affiliation and related ideology in climate change views (9-23% variance), this study underscores the importance of a behavioral health frame in understanding climate change concerns and beliefs. Known risk factors for negative health behaviors - prominently, locus of control, anxiety sensitivity, and delay discounting - contributed strongly to the understanding of these views, accounting for 4-28% of variance. Our findings encourage greater attention to health behavior-related constructs for understanding attitudes relevant to climate change action.

Underscoring the F in FoMO: How does anxiety sensitivity contribute to fear of missing out?

Fear of missing out (FoMO) is a prevalent phenomenon associated with a range of mental health symptoms, such as depression and anxiety. To our knowledge, the question of whether FoMO can be explained by other well-known mechanistic variables-namely, loneliness, rumination, and anxiety sensitivity (AS) - has not been previously evaluated. The current study investigated the predictive power of loneliness, rumination, and AS for explaining variance in FoMO within two independent samples of undergraduate students at a large Northeastern university. Participants completed an online battery of questionnaires. In Study 1, it was found that loneliness and rumination offered significant prediction of FoMO when AS was not considered in the model; however, when these three predictors were considered together, only AS offered significant, non-redundant prediction. Study 2 revealed that both rumination and AS offered significant prediction of FoMO, with AS offering stronger unique prediction. Such findings provide a new frame for understanding the nature of the relatively new concept of FoMO, and in particular, suggest that it may be important to consider AS and rumination in future studies.

Initial assessment of the feasibility and efficacy of a scalable digital CBT for generalized anxiety and associated health behaviors in a cardiovascular disease population.

Generalized anxiety disorder (GAD) is a significant yet modifiable risk factor for worse cardiovascular disease (CVD) outcomes. The treatment of GAD in an accessible manner represents an unmet need in CVD, given that patients with CVD experience numerous barriers to in-person treatment engagement. This paper presents the rationale and design for an investigation of a strategy to enhance care for patients with CVD by introducing a scalable, affordable, and system-friendly digital intervention that targets a prominent modifiable risk factor (generalized anxiety and associated worry) for negative health behaviors in CVD. In the context of a randomized clinical trial design, we describe an experimental medicine approach for evaluating the degree to which a digital cognitive behavior therapy (dCBT), relative to a waitlist control group, engages anxiety and worry outcomes in a sample of 90 adults who have experienced an acute CVD event and who have comorbid GAD symptoms. We also investigate the degree to which dCBT leads to greater changes in GAD symptoms compared to the control condition and whether reductions in these symptoms are associated with corresponding reductions in cardiac anxiety and cardiac health behaviors (including smoking, physical activity, heart-healthy diet, and medication adherence). We propose that by targeting GAD symptoms in CVD in a way that does not tax ongoing medical care provision, we have the potential to improve the uptake of effective care and address both GAD and associated health behaviors.

CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol.

BACKGROUND: Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive-compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction and we have demonstrated that reactivity to an inhaled carbon dioxide (CO2) challenge-a safe, affordable, and easy-to-implement procedure-can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents. Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. METHODS: We will assess CO2 reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open exposure-based therapy. By incorporating CO2 reactivity into a multivariate model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related predictor variables, we will establish the mechanistic specificity and the additive predictive utility of the potential CO2 reactivity biomarker. By developing models independently within two study sites (University of Texas at Austin and Boston University) and predicting the other site's data, we will validate that the results are likely to generalize to future clinical samples. DISCUSSION: Representing a necessary stage in translating basic research, this investigation addresses an important public health issue by testing an accessible clinical assessment strategy that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders, and enhanced understanding of the mechanisms governing exposure-based therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05467683 (20/07/2022).