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.

Novel Approaches Toward Studying Change: Implications for Understanding and Treating Psychopathology.

In this article, the authors critically evaluate contemporary models of psychopathology and therapies, underscoring the limitations of traditional symptom-based classification approaches in mental health. The authors introduce a paradigm shift in the field, toward a process-oriented and dynamic systems approach to psychotherapy that offers deeper insights into the complex interplay of symptoms and individual experiences in psychopathology. These approaches offer a more personalized and effective understanding and treatment of mental health issues, moving beyond static and 1-dimensional views. The authors discuss the implications for clinical practice, emphasizing improved assessment, diagnosis, and tailored treatment strategies.

[Video-Based Online Metta-Meditation Therapy for Depression: A Pilot Trial Evaluating the Acceptability and Feasibility]. / Videobasierte Online-Metta-Meditations-Therapie bei Depression: Eine Pilotstudie zur Bewertung von Akzeptanz und Machbarkeit.

Background: In the course of the Covid-19 pandemic, it has become clear what relevance non-contact psychotherapeutic online interventions in mental health care could possibly have in the future. The present pilot study aims to test whether a Metta-based group program is also an acceptable and feasible treatment when conducted as video-based intervention. Metta meditations aim at showing unconditional benevolence and kindness to oneself and to other people. Methods: Eight patients with depressive disorder participated in a video-based implementation of the Metta-based group program. Quality of the therapeutic relationship, the implementation of methods as well as the acceptance of the video-based therapy on the part of the participants were surveyed as target variables. Results: Data indicated good feasibility in terms of a sustainable therapeutic relationship, the possibility of teaching meditation techniques, and the establishment of a concentrated working atmosphere. Videobased therapy met with good acceptance among the participants. Potential indications for its clinical effectiveness are evident. Conclusion: Teaching Metta meditation in a group program for the treatment of depression can be practicably implemented in a video-based therapy and meets with good acceptance by the patients. Further studies on moderators of acceptance and efficacy of video-based therapy are needed.

Psychological flexibility and cognitive-affective processes in young adults' daily lives.

Psychological flexibility plays a crucial role in how young adults adapt to their evolving cognitive and emotional landscapes. Our study investigated a core aspect of psychological flexibility in young adults: adaptive variability and maladaptive rigidity in the capacity for behavior change. We examined the interplay of these elements with cognitive-affective processes within a dynamic network, uncovering their manifestation in everyday life. Through an Ecological Momentary Assessment design, we collected intensive longitudinal data over 3 weeks from 114 young adults ages 19 to 32. Using a dynamic network approach, we assessed the temporal dynamics and individual variability in flexibility in relation to cognitive-affective processes in this sample. Rigidity exhibited the strongest directed association with other variables in the temporal network as well as highest strength centrality, demonstrating particularly strong associations to other variables in the contemporaneous network. In conclusion, the results of this study suggest that rigidity in young adults is associated with negative affect and cognitions at the same time point and the immediate future.

The Role of Attentional Control in Mindfulness Intervention for Emotional Distress: A Randomized Controlled Trial With Longitudinal Mediation Analyses.

OBJECTIVE: This study aimed to investigate whether attentional control serves as a mediator for mindfulness-based interventions for emotional distress, utilizing a randomized waitlist (WL)-controlled design. METHODS: A total of 498 participants with high emotional distress was recruited online and randomly assigned to a 49-day online Mindfulness Intervention for Emotional Distress (MIED) group (N = 249) or a WL control group (N = 249). Levels of attentional control, anxiety and depression were assessed at baseline (T0), Week 3 (T3), Week 5 (T5) and Week 7 (postintervention, T7). RESULTS: Linear mixed models revealed significant Group-by-Time interaction effects for attentional control (p < 0.001), anxiety (p < 0.001) and depression (p < 0.05). Latent growth curve analyses demonstrated a significant increase in attentional control and a decrease in anxiety and depression levels during the MIED programme. These changes becoming evident starting Week 3. Longitudinal mediation analyses revealed that the slope of attentional control significantly mediated the effects of the MIED programme on the slope of anxiety and depression levels. Further, attentional control level at Week 3 significantly mediates the effect of MIED programme on anxiety and depression levels at Weeks 5 and 7. Similarly, attentional control level at Week 5 significantly mediates the MIED programme's effects on anxiety and depression levels at Week 7. CONCLUSIONS: The present trial provides evidence suggesting that mindfulness interventions may alleviate emotional distress through the enhancement of attentional control. TRIAL REGISTRATION: Chinese Clinical Trial Registry number: ChiCTR2200064140.

The future of psychological treatments: The Marburg Declaration.

Although psychological treatments are broadly recognized as evidence-based interventions for various mental disorders, challenges remain. For example, a substantial proportion of patients receiving such treatments do not fully recover, and many obstacles hinder the dissemination, implementation, and training of psychological treatments. These problems require those in our field to rethink some of our basic models of mental disorders and their treatments, and question how research and practice in clinical psychology should progress. To answer these questions, a group of experts of clinical psychology convened at a Think-Tank in Marburg, Germany, in August 2022 to review the evidence and analyze barriers for current and future developments. After this event, an overview of the current state-of-the-art was drafted and suggestions for improvements and specific recommendations for research and practice were integrated. Recommendations arising from our meeting cover further improving psychological interventions through translational approaches, improving clinical research methodology, bridging the gap between more nomothetic (group-oriented) studies and idiographic (person-centered) decisions, using network approaches in addition to selecting single mechanisms to embrace the complexity of clinical reality, making use of scalable digital options for assessments and interventions, improving the training and education of future psychotherapists, and accepting the societal responsibilities that clinical psychology has in improving national and global health care. The objective of the Marburg Declaration is to stimulate a significant change regarding our understanding of mental disorders and their treatments, with the aim to trigger a new era of evidence-based psychological interventions.

Reverse N-Substituted Hydroxamic Acid Derivatives of Fosmidomycin Target a Previously Unknown Subpocket of 1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase (DXR).

Reverse analogs of the phosphonohydroxamic acid antibiotic fosmidomycin are potent inhibitors of the nonmevalonate isoprenoid biosynthesis enzyme 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR, IspC) of Plasmodium falciparum. Some novel analogs with large phenylalkyl substituents at the hydroxamic acid nitrogen exhibit nanomolar PfDXR inhibition and potent in vitro growth inhibition of P. falciparum parasites coupled with good parasite selectivity. X-ray crystallographic studies demonstrated that the N-phenylpropyl substituent of the newly developed lead compound 13e is accommodated in a subpocket within the DXR catalytic domain but does not reach the NADPH binding pocket of the N-terminal domain. As shown for reverse carba and thia analogs, PfDXR selectively binds the S-enantiomer of the new lead compound. In addition, some representatives of the novel inhibitor subclass are nanomolar Escherichia coli DXR inhibitors, whereas the inhibition of Mycobacterium tuberculosis DXR is considerably weaker.

Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis.

Background: Ketamine and esketamine offer a novel approach in the pharmacological treatment of major depressive disorder (MDD). This meta-analysis aimed to investigate the placebo response in double-blind, randomized controlled studies (RCTs) on patients with MDD receiving ketamine or esketamine. Methods: For this systematic review and meta-analysis Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), PsycInfo and Embase databases were systematically searched for citations published up to March 17, 2023. A total number of 5017 abstracts was identified. Quality of the included trials was assessed with the Cochrane risk-of-bias tool. The meta-analysis was performed using a restricted maximum likelihood model. This study is registered with PROSPERO, number CRD42022377591. Results: A total number of 14 studies and 1100 participants (593 in the medication group and 507 in the placebo group) meeting the inclusion criteria were selected. We estimated the pooled effect sizes of the overall placebo (d pl = -1.85 [CI 95%: -2.9 to -0.79] and overall treatment (dtr = -2.57; [CI 95% -3.36 to -1.78]) response. The overall placebo response accounts for up to 72% of the overall treatment response. Furthermore, we performed subgroup analysis of 8 studies for the for the 7 days post-intervention timepoint. Seven days post-intervention the placebo response (d pl 7d = -1.98 [CI 95%: -3.26 to -0.69]) accounts for 66% of the treatment response (d tr 7d = - 3.01 [CI 95%, -4.28 to -1.74]). Conclusion: Ketamine and esketamine show large antidepressant effects. However, our findings suggest that the placebo response plays a significant role in the antidepressant response and should be used for the benefit of the patients in clinical practice. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022377591.

Vulnerabilities in social anxiety: Integrating intra- and interpersonal perspectives.

What are the major vulnerabilities in people with social anxiety? What are the most promising directions for translational research pertaining to this condition? The present paper provides an integrative summary of basic and applied translational research on social anxiety, emphasizing vulnerability factors. It is divided into two subsections: intrapersonal and interpersonal. The intrapersonal section synthesizes research relating to (a) self-representations and self-referential processes; (b) emotions and their regulation; and (c) cognitive biases: attention, interpretation and judgment, and memory. The interpersonal section summarizes findings regarding the systems of (a) approach and avoidance, (b) affiliation and social rank, and their implications for interpersonal impairments. Our review suggests that the science of social anxiety and, more generally, psychopathology may be advanced by examining processes and their underlying content within broad psychological systems. Increased interaction between basic and applied researchers to diversify and elaborate different perspectives on social anxiety is necessary for progress.

Distress tolerance as a mediator of mindfulness-based intervention for anxiety and depression: Evidence from two randomized controlled trials.

Objective: We aimed to investigate whether distress tolerance mediated the effects of mindfulness-based intervention (MBI) on anxiety and depression with two randomized controlled studies. Method: In Study 1, 374 participants with at least moderate emotional distress were randomized to an intervention group (N = 174) and a waitlist control group (N = 173). Mindfulness, distress tolerance, anxiety, and depression were measured at the pre-test, week 3, week 5, and post-test. In Study 2, 170 participants with emotional disorders were randomized to an intervention group (N = 86) and a control group (N = 84). The same variables were assessed at pre-test, weekly during the intervention, and post-test. Results: In both studies, linear mixed effect models showed that compared to the control group, mindfulness, distress tolerance, anxiety, and depression significantly improved in the intervention group. Parallel process latent growth curve models showed that changes in distress tolerance mediated the effects of the MBI on changes in anxiety and depression. Random-intercept cross-lagged panel models found that distress tolerance temporally preceded depression, but not anxiety. Conclusions: Distress tolerance is a potential mechanism underlying MBIs. Interventions targeting distress tolerance could be embedded in MBIs to enhance the intervention effects for emotional distress.

A Systematic Evaluation of Machine Learning-Based Biomarkers for Major Depressive Disorder.

Importance: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, major depressive disorder (MDD), no informative biomarkers have been identified. Objective: To evaluate whether machine learning (ML) can identify a multivariate biomarker for MDD. Design, Setting, and Participants: This study used data from the Marburg-Münster Affective Disorders Cohort Study, a case-control clinical neuroimaging study. Patients with acute or lifetime MDD and healthy controls aged 18 to 65 years were recruited from primary care and the general population in Münster and Marburg, Germany, from September 11, 2014, to September 26, 2018. The Münster Neuroimaging Cohort (MNC) was used as an independent partial replication sample. Data were analyzed from April 2022 to June 2023. Exposure: Patients with MDD and healthy controls. Main Outcome and Measure: Diagnostic classification accuracy was quantified on an individual level using an extensive ML-based multivariate approach across a comprehensive range of neuroimaging modalities, including structural and functional magnetic resonance imaging and diffusion tensor imaging as well as a polygenic risk score for depression. Results: Of 1801 included participants, 1162 (64.5%) were female, and the mean (SD) age was 36.1 (13.1) years. There were a total of 856 patients with MDD (47.5%) and 945 healthy controls (52.5%). The MNC replication sample included 1198 individuals (362 with MDD [30.1%] and 836 healthy controls [69.9%]). Training and testing a total of 4 million ML models, mean (SD) accuracies for diagnostic classification ranged between 48.1% (3.6%) and 62.0% (4.8%). Integrating neuroimaging modalities and stratifying individuals based on age, sex, treatment, or remission status does not enhance model performance. Findings were replicated within study sites and also observed in structural magnetic resonance imaging within MNC. Under simulated conditions of perfect reliability, performance did not significantly improve. Analyzing model errors suggests that symptom severity could be a potential focus for identifying MDD subgroups. Conclusion and Relevance: Despite the improved predictive capability of multivariate compared with univariate neuroimaging markers, no informative individual-level MDD biomarker-even under extensive ML optimization in a large sample of diagnosed patients-could be identified.

The Relationship Between Psychological Inflexibility and Well-Being in Adults: A Meta-Analysis of the Acceptance and Action Questionnaire.

Psychological inflexibility is defined as the rigid responding to stimuli (e.g., unpleasant thoughts and feelings) that interferes with well-being and valued actions. It is the treatment target in acceptance and commitment therapy (ACT). Despite the centrality of the link between inflexibility and well-being to ACT theory, an empirical review clarifying the nature of this relationship has not been conducted. As such, the current meta-analysis examined the meta-correlation between psychological inflexibility, measured by the Acceptance and Action Questionnaire (AAQ) and its variants, and well-being. A systematic review yielded 151 studies, including 25 versions of the AAQ and 43 well-being measures. Consistent with ACT theory, higher psychological inflexibility was associated with worse well-being (r = -.47, 95% CI[-.49, -.45]). In addition, sample diagnosis, type of AAQ, and type of well-being measure significantly moderated this relationship. Overall, our findings support the hypothesized link between psychological inflexibility and worse well-being. Limitations include reliance on cross-sectional data, precluding causal interpretation.

The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

Effect of cognitive behavioural therapy and yoga for generalised anxiety disorder on sleep quality in a randomised controlled trial: the role of worry, mindfulness, and perceived stress as mediators.

Sleep disturbances are present in ~65% of individuals with generalised anxiety disorder (GAD). Although both Kundalini yoga (KY) and cognitive behavioural therapy (CBT) are effective treatment options for GAD, little is known about how these treatments compare in improving sleep for GAD and what drives these changes. Accordingly, we examined the effects of CBT, KY, and stress education (SEdu; an attention control condition) on subjective sleep quality (as measured by the Pittsburgh Sleep Quality Index [PSQI] and Insomnia Severity Index [ISI]) in a randomised controlled trial of 226 adults with GAD (mean age 33.37 years; 70% female; 79% White). We hypothesised that both CBT and KY would outperform SEdu in improving sleep disturbances. Three potential mediators of sleep improvement (worry, mindfulness, perceived stress) were also examined. In line with hypotheses, PSQI and ISI scores significantly improved from pre- to post-treatment for all three treatment groups (all p < 0.001, all d > 0.97). However, contrary to predictions, sleep changes were not significantly greater for CBT or KY compared to SEdu. In mediation analyses, within-person deviations in worry, mindfulness, and stress each significantly mediated the effect of time on sleep outcomes. Degree of change in sleep attributable to worry (CBT > KY > SEdu) and perceived stress (CBT, KY > SEdu) was moderated by treatment group. Personalised medicine as well as combined treatment approaches should be studied to help reduce sleep difficulties for patients with GAD who do not respond.

A biphasic relational approach to the evolution of human consciousness

Background/objective: Human consciousness is arguably unique, and its features are hard to explain. Continuous and discrete accounts of consciousness are commonly viewed as incompatible, but both have limitations. Continuous accounts cannot readily account for what appears to be unique about human consciousness; discrete accounts have a hard time explaining how human consciousness could have evolved. The present position paper shows how both continuous and discontinuously elements can be combined. Method: A biphasic model is constructed by unifying complex systems theory, the evolution of symbolic reasoning as a relational extension of human cooperation, and evolutionary science. The application of this approach to modern views of consciousness is then explored. Results: Our analysis suggests that human consciousness may be viewed as a discontinuous event, that emerged from continuous foundations. This biphasic account contains processes that can be targeted clinically. For example, developmentally delayed children with problems in consciousness may be helped by targeting the processes the present account suggests are important at different levels of complexity. Conclusions: This biphasic relational approach fits with the evolutionary record and with data on human cognitive development. It may be useful in guiding clinical intervention. (AU)

Distress tolerance as a mechanism of mindfulness for depression and anxiety: Cross-sectional and diary evidence

Background: Both trait and state mindfulness are associated with less depression and anxiety, but the mechanisms remain unknown. Distress tolerance, an important transdiagnostic factor of emotional disorders, may mediate the relationship between mindfulness and depression/anxiety. Method: Study 1 examined the mediation model at the between-person level in a large cross-sectional sample (n = 905). In Study 2, a daily diary study (n = 110) was conducted to examine within-person changes. Participants were invited to complete daily diaries measuring daily mindfulness, distress tolerance, depression and anxiety for 14 consecutive days. Results: In Study 1, results of simple mediation analyses indicated that distress tolerance mediated the relationship between mindfulness and depression/anxiety at the between-person level. In Study 2, results of multilevel mediation analyses indicated that, in both the concurrent model and time-lagged model, daily distress tolerance mediated the effects of daily mindfulness on daily depression/anxiety at both the within- and between-person level. Conclusions: Distress tolerance is a mechanism underlying the relationship between mindfulness and depression/anxiety. Individuals with high or fluctuating depression and anxiety may benefit from short-term or long-term mindfulness training to increase distress tolerance. (AU)

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.

The Idionomic Future of Cognitive Behavioral Therapy: What Stands Out From Criticisms of ACT Development.

The present special section critical of Acceptance and Commitment Therapy or Training (ACT in either case) and its basis in psychological flexibility, relational frame theory, functional contextualism, and contextual behavioral science (CBS) contains both worthwhile criticisms and fundamental misunderstandings. Noting the important historical role that behavior analysis has played in the cognitive behavioral therapy (CBT) tradition, we argue that CBS as a modern face of behavior analytic thinking has a potentially important positive role to play in CBT going forward. We clarify functional contextualism and its link to ethical behavior, attempting to clear up misunderstandings that could seriously undermine genuine scientific conversations. We then examine the limits of using syndromes and protocols as a basis for further developing models and methods; the role of measurement and processes of change in driving progress toward more personalized interventions; how pragmatically useful concepts can help basic science inform practice; how both small- and large-scale studies can contribute to scientific progress; and how all these strands can be pulled together to benefit humanity. In each area, we argue that further progress will require major modifications in our traditional approaches to such areas as psychometrics, the conduct of randomized trials, the analysis of findings using traditional normative statistics, and the use of data from diverse cultures and marginalized populations. There have been multiple generational shifts in our field's history, and a similar shift appears to be taking place once again.