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.

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.

Cognitive Effects of Reducing First-Generation Antipsychotic Dose Compared to Switching to Ziprasidone in Long-Stay Patients with Schizophrenia.

Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect.

Low reliability when determining criterion a for posttraumatic stress disorder from self-report descriptions of traumatic events: The need for transparent methods.

OBJECTIVE: Exposure to a traumatic event is a primary criterion (Criterion A) for meeting Posttraumatic Stress Disorder (PTSD). Using self-report to establish diagnostic criteria in research has become more common, especially with internet-based research. However, some individuals may construe events as traumatic when they do not meet Criterion A. There has yet to be a test of interrater reliability (IRR) from self-report of traumatic events. METHOD: Three graduate students in clinical psychology and three licensed psychologists rated Criterion A using the life events checklist (LEC), as well as the three modified LEC versions (specification of up to three index traumas; extension of part 2 of the LEC) aimed to increase IRR. One hundred participants completed each of the four versions of the LEC (N = 400). Bootstrapped permutation tests were used to estimate differences in IRR and to generate 95% confidence intervals (CIs). RESULTS: Overall, findings indicated fair-moderate IRR (Fleiss's kappa) κ = 0.428, 95% CI [0.379, 0.477]. The other versions of the LEC (including additional clarifying questions in part 2 of the LEC and/or opportunities to describe up to three traumas) did not meaningfully increase IRR. CONCLUSIONS: Findings indicate that relying on self-report from the LEC alone and/or single-rater assessment of open-text trauma descriptions is not recommended for determining whether a traumatic event meets Criterion A. We conclude that it is critical when collecting self-reported PTSD symptoms to provide a clear description of how Criterion A was assessed, initial agreement between raters, and how disagreements were resolved. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Artificial Intelligence-Based Video Feedback to Improve Novice Performance on Robotic Suturing Skills: A Pilot Study.

Introduction: Automated skills assessment can provide surgical trainees with objective, personalized feedback during training. Here, we measure the efficacy of artificial intelligence (AI)-based feedback on a robotic suturing task. Materials and Methods: Forty-two participants with no robotic surgical experience were randomized to a control or feedback group and video-recorded while completing two rounds (R1 and R2) of suturing tasks on a da Vinci surgical robot. Participants were assessed on needle handling and needle driving, and feedback was provided via a visual interface after R1. For feedback group, participants were informed of their AI-based skill assessment and presented with specific video clips from R1. For control group, participants were presented with randomly selected video clips from R1 as a placebo. Participants from each group were further labeled as underperformers or innate-performers based on a median split of their technical skill scores from R1. Results: Demographic features were similar between the control (n = 20) and feedback group (n = 22) (p > 0.05). Observing the improvement from R1 to R2, the feedback group had a significantly larger improvement in needle handling score (0.30 vs -0.02, p = 0.018) when compared with the control group, although the improvement of needle driving score was not significant when compared with the control group (0.17 vs -0.40, p = 0.074). All innate-performers exhibited similar improvements across rounds, regardless of feedback (p > 0.05). In contrast, underperformers in the feedback group improved more than the control group in needle handling (p = 0.02). Conclusion: AI-based feedback facilitates surgical trainees' acquisition of robotic technical skills, especially underperformers. Future research will extend AI-based feedback to additional suturing skills, surgical tasks, and experience groups.

Fire-modulated fluctuations in nutrient availability stimulate biome-scale floristic turnover in time, and elevated species richness, in low-nutrient fynbos heathland.

BACKGROUND AND AIMS: In many systems, postfire vegetation recovery is characterized by temporal changes in plant species composition and richness. We attribute this to changes in resource availability with time since fire, with the magnitude of species turnover determined by the degree of resource limitation. Here, we test the hypothesis that postfire species turnover in South African fynbos heathland is powered by fire-modulated changes in nutrient availability, with the magnitude of turnover in nutrient-constrained fynbos being greater than in fertile renosterveld shrubland. We also test the hypothesis that floristic overlaps between fynbos and renosterveld are attributable to nutritional augmentation of fynbos soils immediately after fire. METHODS: We use vegetation survey data from two sites on the Cape Peninsula to compare changes in species richness and composition with time since fire. KEY RESULTS: Fynbos communities display a clear decline in species richness with time since fire, whereas no such decline is apparent in renosterveld. In fynbos, declining species richness is associated with declines in the richness of plant families having high foliar concentrations of nitrogen, phosphorus and potassium and possessing attributes that are nutritionally costly. In contrast, families that dominate late-succession fynbos possess adaptations for the acquisition and retention of sparse nutrients. At the family level, recently burnt fynbos is compositionally more similar to renosterveld than is mature fynbos. CONCLUSIONS: Our data suggest that nutritionally driven species turnover contributes significantly to fynbos community richness. We propose that the extremely low baseline fertility of fynbos soils serves to lengthen the nutritional resource axis along which species can differentiate and coexist, thereby providing the opportunity for low-nutrient extremophiles to coexist spatially with species adapted to more fertile soil. This mechanism has the potential to operate in any resource-constrained system in which episodic disturbance affects resource availability.

Defining trimester-specific reference intervals for carbohydrate deficient transferrin in pregnant women.

OBJECTIVES: Extensive consumption of alcohol during pregnancy can lead to severe complications for the unborn child. Carbohydrate-deficient transferrin (CDT) levels in serum have become a common biomarker for excessive alcohol intake. However, during pregnancy CDT levels can rise to levels above commonly used cut-off values, for reasons unrelated to alcohol intake. The aim of this study is to investigate the changes in CDT values during pregnancy and to determine accurate, trimester dependent reference intervals. METHODS: 439 serum samples of 147 healthy pregnant women were obtained for trimester 1, 2, 3, and post-partum and were analysed by high-performance liquid chromatography (HPLC) and an N-Latex immunonephelometric assay. New trimester-specific reference intervals were established. RESULTS: This study demonstrates there is a trimester-dependent increase of %CDT, as up to 39.4% of the population exceeded the previously established upper reference limit of 1.7%. In our study the estimated upper reference limit for %DST/%CDT were 1.55%, 1.96%, 2.05% and 1.35% for trimester 1, 2, 3 and post-partum for the HPLC-method and 2.02%, 2.19%, 2.19% and 1.96% for the N-Latex immunoassay. CONCLUSIONS: We demonstrate that CDT levels rise during pregnancy. The magnitude of the increase is method-dependent and needs to be taken into account. We have established method- and trimester-specific reference intervals to prevent false-positive results in alcohol abuse screening tests during pregnancy.

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.

Social avoidance and testosterone enhanced exposure efficacy in women with social anxiety disorder: A pilot investigation.

Social avoidance has been associated with more persistent social anxiety disorder (SAD) symptoms and low testosterone levels in individuals with SAD. We tested whether pre-treatment avoidance tendencies moderate the efficacy of testosterone-augmented exposure therapy. Fifty-five females with SAD received two exposure sessions during which fear levels were assessed. Session 1 was augmented with testosterone (0.50 mg) or placebo. Avoidance tendencies and symptom severity were assessed pre- and post-exposure. Participants showed stronger avoidance for social versus non-social stimuli and this tendency remained stable over time. Stronger pretreatment avoidance tendencies were associated with larger fear reduction in the testosterone but not the placebo condition. This effect did not transfer to the second non-enhanced session or symptom severity. The findings support the hypothesis that individuals suffering from SAD with relatively stronger pretreatment avoidance tendencies benefit more from testosterone-augmentation, pointing to a potential behavioral marker for testosterone enhancement of exposure therapy.

Holocene climate change in southern Oman deciphered by speleothem records and climate model simulations.

Qunf Cave oxygen isotope (δ18Oc) record from southern Oman is one of the most significant of few Holocene Indian summer monsoon cave records. However, the interpretation of the Qunf δ18Oc remains in dispute. Here we provide a multi-proxy record from Qunf Cave and climate model simulations to reconstruct the Holocene local and regional hydroclimate changes. The results indicate that besides the Indian summer monsoon, the North African summer monsoon also contributes water vapor to southern Oman during the early to middle Holocene. In principle, Qunf δ18Oc values reflect integrated oxygen-isotope fractionations over a broad moisture transport swath from moisture sources to the cave site, rather than local precipitation amount alone, and thus the Qunf δ18Oc record characterizes primary changes in the Afro-Asian monsoon regime across the Holocene. In contrast, local climate proxies appear to suggest an overall slightly increased or unchanged wetness over the Holocene at the cave site.

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.

The spatiotemporal extent of the Green Sahara during the last glacial period.

The Sahara Desert, one of today's most inhospitable environments, has known periods of enhanced precipitation that supported pre-historic humans. However, the Green Sahara timing and moisture sources are not well known due to limited paleoclimate information. Here, we present a multi-proxy (δ18O, δ13C, Δ17O, and trace elements) speleothem-based climate record from Northwest (NW) Africa. Our data document two Green Sahara periods during Marine Isotope Stage (MIS) 5a and the Early to Mid-Holocene. Consistency with paleoclimate records across North Africa highlights the east-west geographical extent of the Green Sahara, whereas millennial-scale North Atlantic cooling (Heinrich) events consistently resulted in drier conditions. We demonstrate that an increase in westerly-originating winter precipitation during MIS5a resulted in favorable environmental conditions. The comparison of paleoclimate data with local archaeological sequences highlights the abrupt climate deterioration and the decline in human density in NW Africa during the MIS5-4 transition, which suggests climate-forced dispersals of populations, with possible implications for pathways into Eurasia.

Limited climatic space for alternative ecosystem states in Africa.

One of the foundational premises of ecology is that climate determines ecosystems. This has been challenged by alternative ecosystem state models, which illustrate that internal ecosystem dynamics acting on the initial ecosystem state can overwhelm the influence of climate, and by observations suggesting that climate cannot reliably discriminate forest and savanna ecosystem types. Using a novel phytoclimatic transform, which estimates the ability of climate to support different types of plants, we show that climatic suitability for evergreen trees and C4 grasses are sufficient to discriminate between forest and savanna in Africa. Our findings reassert the dominant influence of climate on ecosystems and suggest that the role of feedbacks causing alternative ecosystem states is less prevalent than has been suggested.

Behavioral responses of terrestrial mammals to COVID-19 lockdowns.

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

Tabernanthalog Reduces Motivation for Heroin and Alcohol in a Polydrug Use Model.

Background: The potential use of psychedelic drugs as therapeutics for neuropsychiatric disorders has been limited by their hallucinogenic properties. To overcome this limitation, we developed and characterized tabernanthalog (TBG), a novel analogue of the indole alkaloids ibogaine and 5-methoxy-N,N-dimethyltryptamine with reduced cardiac arrhythmogenic risk and a lack of classical psychedelic drugs-induced sensory alterations. We previously demonstrated that TBG has therapeutic efficacy in a preclinical model of opioid use disorder (OUD) in rats and in a binge model of alcohol drinking in mice. Alcohol is commonly co-used in ∼35-50% of individuals with OUD, and yet, preclinical models that recapitulate this comorbidity are lacking. Methodology: Here we employed a polydrug model of heroin and alcohol couse to screen the therapeutic efficacy of TBG on metrics of both opioid and alcohol seeking. We first exposed rats to alcohol (or control sucrose-fade solution) in the home-cage (HC), using a two-bottle binge protocol, over a period of 1 month. Rats were then split into two groups that underwent self-administration training for either intravenous heroin or oral alcohol, so that we could assess the impact of HC alcohol exposure on the self-administration of each substance separately. Thereafter, rats began self-administering both heroin and alcohol in the same sessions. Finally, we tested the effects of TBG on break points for heroin and alcohol in a progressive ratio test, where the number of lever presses required to obtain a single reward increased exponentially. Results and Conclusion: TBG effectively reduced motivation for heroin and alcohol in this test, indicating its efficacy is preserved in animals with a history of heroin and alcohol polydrug use.

The Relationship Between Cigarette Dependence and Cessation Methods: Implications for Smoking Cessation Among People With HIV.

OBJECTIVE: These analyses investigate how dependence may be related to cessation method choice and how this relationship may vary by subpopulation among people with HIV (PWH) who smoke cigarettes. METHOD: PWH who smoke (N = 71) were recruited from clinics in Boston, MA. The Fagerström Test for Nicotine Dependence (FTND) and Smoking History Questionnaire (SHQ) were completed to assess for cigarette dependence, past-week cigarettes per day (CPD), and past cessation method use. Logistic regression examined the association between dependence and previous cessation methods for the whole sample, and moderation analyses assessed this relationship by age and race. RESULTS: Higher FTND was associated with less use of behavioral modification methods (odds ratio [OR] = 0.658, 95% CI [0.435, 0.994], p = .047). Higher past-week CPD was associated with use of the American Cancer Society/American Lung Association (ACS/ALA) programs (OR = 1.159, 95% CI [1.011, 1.328], p = .035) and telephone counselling (OR = 1.142, 95% CI [1.006, 1.295], p = .040]). Older participants with more past-week CPD were more likely to have used the ACS/ALA programs (B = 0.0169, 95% CI [0.0008, 0.0331], p = .0401), and White participants with more past-week CPD were less likely to have tried to quit "cold turkey" (B = 0.1676, 95% CI [0.0027, 0.3326], p = .0464). CONCLUSIONS: These preliminary results suggest that there is likely not a "one-size-fits-all" approach to cessation for PWH who smoke, especially within subpopulations (i.e., age and race). Implications include ensuring access to multiple cessation methods, identifying methods that could be culturally appropriate outside of the clinical intervention setting, and providing education and support on cessation methods offered.

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.

Study protocol for approach bias retraining for nicotine addiction among dual combustible and electronic cigarette users.

BACKGROUND: Electronic cigarette (ECIG) use has become a popular method for nicotine delivery. Combustible cigarette (CC) cessation or reduction are the primary reasons for ECIG uptake among adults. Yet, most CC smokers who initiate ECIG use do not fully transition from CC to ECIG, despite intending to quit CC completely. Retraining approach bias, or the approach action tendency toward stimuli related to the substance of interest, has been effective in alcohol and CC use treatments. However, approach bias retraining for both CC and (ECIG) users has not been explored. Therefore, the objective of the study is to evaluate the initial efficacy of approach bias retraining among dual CC and ECIG users. METHODS: Eligible dual CC/ECIG using adults (N = 90) will complete a phone-screener, baseline assessment, 4 treatment sessions over 2 weeks, ecological momentary assessments (EMAs) post-intervention, and follow-ups at 4- and 6-week post-intervention. Participants will be assigned to one of three conditions at baseline: (1) CC + ECIG retraining; (2) CC only retraining; and (3) sham retraining. Participants will engage in a self-guided quit attempt to abstain from all nicotine products starting at treatment session 4. CONCLUSIONS: The study may lead to a more effective treatment for at-risk nicotine users while simultaneously isolating explanatory mechanisms. The findings should guide advances in the theoretical conceptualization of nicotine addiction for dual users and mechanisms involved in maintaining and abstaining from CC and ECIG, and provide initial effect size data for a brief intervention, thus providing necessary data for a large-scale follow-up trial. Clinical Trials ID: NCT05306158.