Demonstration of a 'leapfrog' randomized controlled trial as a method to accelerate the development and optimization of psychological interventions.

BACKGROUND: The scale of the global mental health burden indicates the inadequacy not only of current treatment options, but also the pace of the standard treatment development process. The 'leapfrog' trial design is a newly-developed simple Bayesian adaptive trial design with potential to accelerate treatment development. A first leapfrog trial was conducted to provide a demonstration and test feasibility, applying the method to a low-intensity internet-delivered intervention targeting anhedonia. METHODS: At the start of this online, single-blind leapfrog trial, participants self-reporting depression were randomized to an initial control arm comprising four weeks of weekly questionnaires, or one of two versions of a four-week cognitive training intervention, imagery cognitive bias modification (imagery CBM). Intervention arms were compared to control on an ongoing basis via sequential Bayesian analyses, based on a primary outcome of anhedonia at post-intervention. Results were used to eliminate and replace arms, or to promote them to become the control condition based on pre-specified Bayes factor and sample size thresholds. Two further intervention arms (variants of imagery CBM) were added into the trial as it progressed. RESULTS: N = 188 participants were randomized across the five trial arms. The leapfrog methodology was successfully implemented to identify a 'winning' version of the imagery CBM, i.e. the version most successful in reducing anhedonia, following sequential elimination of the other arms. CONCLUSIONS: The study demonstrates feasibility of the leapfrog design and provides a foundation for its adoption as a method to accelerate treatment development in mental health. Registration: clinicaltrials.gov, NCT04791137.

The Effects of Modifying Dysfunctional Appraisals in Posttraumatic Stress Disorder Using a Form of Cognitive Bias Modification: Results of a Randomized Controlled Trial in an Inpatient Setting.

INTRODUCTION: Dysfunctional appraisals about traumatic events and their sequelae are a key mechanism in posttraumatic stress disorder (PTSD). Experimental studies have shown that a computerized cognitive training, cognitive bias modification for appraisals (CBM-APP), can modify dysfunctional appraisals and reduce analogue trauma symptoms amongst healthy and subclinical volunteers. OBJECTIVE: We aimed to test whether CBM-APP could reduce dysfunctional appraisals related to trauma reactions in PTSD patients, and whether this would lead to improvements in PTSD symptoms. METHODS: We compared CBM-APP to sham training in a parallel-arm proof-of-principle double-blind randomized controlled trial amongst 80 PTSD patients admitted to an inpatient clinic. Both arms comprised a training schedule of 8 sessions over a 2-week period and were completed as an adjunct to the standard treatment programme. RESULTS: In intention-to-treat analyses, participants receiving CBM-APP showed a greater reduction in dysfunctional appraisals on a scenario task from pre- to posttraining (primary outcome) assessments, compared to those receiving sham training (d = 1.30, 95% CI 0.82-1.80), with between-group differences also found on the Posttraumatic Cognitions Inventory (PTCI; d = 0.85, 95% CI 0.39-1.32) and the PTSD Checklist for DSM-5 (PCL-5; d = 0.68, 95% CI 0.23-1.14), but not for long-term cortisol concentrations (d = 0.25, 95% CI -0.28 to 0.78). Reductions in dysfunctional appraisals assessed via the scenario task correlated with reductions on the PTCI, PCL-5, and hair cortisol concentrations from pre- to posttraining time points. CONCLUSIONS: Results support dysfunctional appraisals as a modifiable cognitive mechanism, and that their proximal modification transfers to downstream PTSD symptoms. These findings could open new avenues for improving present therapeutic approaches.

Using Three Indirect Measures to Assess the Role of Sexuality-Related Associations and Interpretations for Women's Sexual Desire: An Internet-Based Experimental Study.

Theoretical models emphasize the role of both automatic appraisals (i.e., associations) and conscious appraisals (i.e., interpretations) for sexual desire. Studies on sexuality-related appraisals have not combined self-report measures and experimental paradigms in order to compare the relevance of associations or interpretations. The aim of this study was to assess the relative contribution of both associations and interpretations to the explanation of low sexual desire in women. Toward this goal, indirect measures assessing associations (via a Single Target Implicit Association Test [STIAT]) and interpretations (via a Scrambled Sentences Test [SST] and a scenario task) were administered in a sample of 263 women (Mage = 27.90, SD 8.27) with varying levels of sexual desire and different sexual orientations (exclusively heterosexual women: 54.6%). Negative sexuality-related interpretations as assessed with two variants of the SST as well as the scenario task added to the explanation of lower sexual desire in women. Negative associations as measured with the STIAT were predictive of lower sexual desire only in women who did not indicate an exclusively heterosexual orientation. In this study, sexuality-related interpretations were more relevant to women's sexual desire than automatic associations. Future studies should assess the causal mechanism underlying sexuality-related interpretations (e.g., by evaluating whether these can be changed via cognitive bias modification techniques or psychological treatments).

Inducing positive involuntary mental imagery in everyday life: an experimental investigation.

Positive involuntary mental imagery occurs frequently in daily life but evidence as to its functions and importance is largely indirect. The current study investigated a method to induce positive involuntary imagery in daily life, which would allow direct testing of its impact. An unselected student sample (N = 80) completed a single session of a positive imagery cognitive bias modification (CBM) paradigm, which involved listening to and imagining brief positive imagery scripts. Participants then recorded any involuntary memories of the imagined training scenarios in a three-day diary before returning to the lab for a follow-up assessment. Participants were randomised to imagine the scenarios in either an emotionally involved or emotionally detached manner, providing a test of the role of emotion in the subsequent experience of involuntary memories. Participants reported experiencing involuntary memories of the training scenarios in their daily life, but the number recorded did not differ between the experimental conditions. Exploratory analyses suggested that more vivid imagery and recall testing were associated with a greater number of involuntary memories. The study highlights the potential of the imagery CBM paradigm to further our understanding of the functions and potential importance of positive involuntary mental imagery in daily life.

Assessing Cognitive Appraisals Related to Sexual Function: A Scenario-Based Approach.

Cognitive factors play an important role in the etiology and maintenance of sexual difficulties. To date, research has mostly relied on self-report measures to assess negative cognitions related to low sexual function. To overcome the limitations of self-report questionnaires, a series of open-ended, ambiguous sexual scenarios were developed and presented to participants (N = 600, Mage = 34.2 years), who were asked to generate an ending by entering a continuation for each scenario. Valence of completed scenarios was rated by the participants, and scenario endings were coded by two independent raters on three dimensions, namely reference to sexual problems, sexual communication, and the use of sexually explicit language. Sexual function was assessed with the Female Sexual Function Index and the International Index of Erectile Function. Multiple regression analyses were performed to assess whether the scenario-based task was associated with sexual function above and beyond other predictors (e.g., sexual distress). Individuals with lower sexual function rated the completed scenarios more negatively, and their endings included more references to problems related to low sexual function. In women with low sexual function, fewer endings included sexual communication with a partner or sexually explicit language. Our findings suggest that individuals with low sexual function appraise ambiguous sexual situations more negatively than other individuals. Future studies may investigate whether such biases can be experimentally manipulated and whether changes in cognitive biases may, in turn, lead to improvements in sexual function.

The role of KIBRA in reconstructive episodic memory.

BACKGROUND: In order to retrieve episodic past events, the missing information needs to be reconstructed using information stored in semantic memory. Failures in these reconstructive processes are expressed as false memories. KIBRA single nucleotide polymorphism (rs17070145) has been linked to episodic memory performance as well as an increased risk of Alzheimer's disease and post-traumatic stress disorder (PTSD). METHODS: Here, the role of KIBRA rs17070145 polymorphism (male and female CC vs. CT/TT carriers) in reconstructive episodic memory in the Deese-Roediger-McDermott (DRM) paradigm was investigated in N = 219 healthy individuals. RESULTS: Female participants outperformed males in the free recall condition. Furthermore, a trend towards a gender x genotype interaction was found for false recognition rates. Female CT/TT carriers exhibited a lower proportion of false recognition rates for associated critical lures as compared to male CT/TT. Additionally, an association between KIBRA rs17070145 genotype, familiarity and recollection based recognition performance was found. In trials with correct recognition of listed items CT/TT carriers showed more "remember", but fewer "know" responses as compared to CC carriers. DISCUSSION AND CONCLUSION: Our findings suggest that the T-allele of KIBRA rs17070145 supports recollection based episodic memory retrieval and contributes to memory accuracy in a gender dependent manner. Findings are discussed in the context of the specific contribution of KIBRA related SNPs to reconstructive episodic memory and its implications for cognitive and emotional symptoms in dementia and PTSD.

Do health-related factors predict major depression? A longitudinal epidemiologic study.

Major depressive disorder (MDD) is a leading cause of global disease burden. Hence, examining the role of risk and protective factors for MDD is an important target in psychological research. Various studies showed that obesity, smoking, and alcohol consumption are related to depressive symptoms. In contrast, physical activity has been found to be a protective factor. The present population-based study tested whether these health-related factors are prospectively associated with incidence of MDD. Data were taken from the Dresden Predictor Study, which was designed to investigate risk and protective factors of mental health in young women. It included two assessments approximately 17 months apart. Results of single logistic regression analyses showed that being overweight, being a smoker, and being in a high-risk drinking group at baseline were predictive of developing MDD at follow-up. Engaging in regular physical activity and having good physical health were found to be protective factors of MDD. However, being in a medium-risk drinking group was not predictive of incidence of MDD, and irregular physical activity was not a protective factor. This is the first prospective, longitudinal study to show that obesity, smoking, and high-risk drinking are predictive of new onsets of MDD and that physical health is a protective factor. These data provide promising avenues for future research.

Alcohol-related interpretation bias in alcohol-dependent patients.

BACKGROUND: Models of addictive behaviors postulate that implicit alcohol-related memory associations and biased interpretation processes contribute to the development and maintenance of alcohol misuse and abuse. The present study examined whether alcohol-dependent patients (AP) show an alcohol-related interpretation bias. Second, the relationship between the interpretation bias and levels of harmful drinking was investigated. METHODS: The sample included 125 clinically diagnosed AP and 69 clinically diagnosed control patients (CP) who had either a mood or an anxiety disorder. Participants completed a booklet containing 12 open-ended ambiguous scenarios. Seven scenarios were alcohol-relevant, and 5 were emotionally relevant, that is, panic- or depression-relevant. Participants were asked to read each scenario and to generate a continuation. In addition, the Alcohol Use Disorder Identification Test (AUDIT) and Beck Depression Inventory were administered. RESULTS: Logistic multivariate multilevel analyses revealed that AP' probability of generating an alcohol-related continuation on all 3 scenario types was higher than that of CP. Moreover, alcohol-related interpretation biases were positively associated with levels of harmful drinking (i.e., AUDIT scores). CONCLUSIONS: These findings are the first to show that AP show an alcohol-related interpretation bias, which generalizes to other ambiguous emotionally relevant contexts, and therefore advance our understanding of the role of implicit biased alcohol-related memory associations and interpretation processes.

Nicotine-related interpretation biases in cigarette smoking individuals.

Addictive behaviors are characterized by information processing biases, including substance-related interpretation biases. In the field of cigarette smoking, such biases have not been investigated yet. The present study thus adopted an open-ended scenario approach to measure smoking-related interpretation biases. Individuals who smoke, those who ceased smoking, and those without a smoking history (total sample N = 177) were instructed to generate spontaneous continuations for ambiguous, open-ended scenarios that described either a smoking-related or neutral context. Overall, people who smoke generated more smoking-related continuations in response to smoking-relevant situations than non-smoking individuals or people who had stopped smoking, providing evidence for a smoking-related interpretation bias. When differentiating for situation type within smoking-relevant scenarios, smoking individuals produced more smoking-related continuations for positive/social and habit/addictive situations compared to negative/affective ones. Additionally, the tendency to interpret habit/addictive situations in a smoking-related manner was positively associated with cigarette consumption and levels of nicotine dependence. Exploratory analyses indicated that other substance-related continuations were correlated with their respective behavioral counterparts (e.g., the level of self-reported alcohol or caffeine consumption). The present study is the first to demonstrate smoking-related interpretation biases in relation to current cigarette smoking. Future studies should investigate the causal role of such biases in the initiation and/or maintainance of nicotine addiction and the merit of Interpretation-Bias-Modification training to support smoking cessation.

The relationship between the perception of major life events and depression: A systematic scoping review and meta-analysis.

BACKGROUND: Major life events can lead to depression in adulthood. However, as predicted by several depression theories, not only the mere occurrence of major life events but also the way people perceive them determines the onset of a depression. METHODS: Based on a systematic literature search, we identified 276 studies (Ntotal = 89,600) that examined the relationship between the perception of major life events and depression. We provide an overview of how this relationship has been examined. Furthermore, we meta-analytically integrated 420 effect sizes (172 studies) on the association between the perception of major life events and depression. RESULTS: Most studies relied on college student samples, were cross-sectional, and were conducted in the United States. A more negative perception of events was significantly associated with higher levels of depressive symptoms (r = 0.28). This association was robust across several design and sample characteristics. Furthermore, the perception of major life events and depression were also longitudinally associated with each other (event perception predicting later depressive symptoms: r = 0.26; depressive symptoms predicting later event perception: r = 0.17). LIMITATIONS: Longitudinal research on the relationship between depression and the perception of major life events was relatively rare impairing definite conclusions on whether the perception of life events can predict changes in depressive symptoms over time. CONCLUSION: The perception of major life events is related to depression. However, further longitudinal research considering a range of different perceived event characteristics and using non-Western heterogeneous samples is needed to better understand their relationship.

Towards implementation of cognitive bias modification in mental health care: State of the science, best practices, and ways forward.

Cognitive bias modification (CBM) has evolved from an experimental method testing cognitive mechanisms of psychopathology to a promising tool for accessible digital mental health care. While we are still discovering the conditions under which clinically relevant effects occur, the dire need for accessible, effective, and low-cost mental health tools underscores the need for implementation where such tools are available. Providing our expert opinion as Association for Cognitive Bias Modification members, we first discuss the readiness of different CBM approaches for clinical implementation, then discuss key considerations with regard to implementation. Evidence is robust for approach bias modification as an adjunctive intervention for alcohol use disorders and interpretation bias modification as a stand-alone intervention for anxiety disorders. Theoretical predictions regarding the mechanisms by which bias and symptom change occur await further testing. We propose that CBM interventions with demonstrated efficacy should be provided to the targeted populations. To facilitate this, we set a research agenda based on implementation frameworks, which includes feasibility and acceptability testing, co-creation with end-users, and collaboration with industry partners.

Effects of approach-avoidance training on implicit and explicit evaluations of neutral, angry, and smiling face stimuli.

A growing body of evidence shows that the prolonged execution of approach movements towards stimuli and avoidance movements away from them affects their evaluation. However, there has been no systematic investigation of such training effects. Therefore, the present study compared approach-avoidance training effects on various valenced representations of one neutral (Experiment 1, N = 85), angry (Experiment 2, N = 87), or smiling facial expressions (Experiment 3, N= 89). The face stimuli were shown on a computer screen, and by means of a joystick, participants pulled half of the faces closer (positive approach movement), and pushed the other half away (negative avoidance movement). Only implicit evaluations of neutral-expression were affected by the training procedure. The boundary conditions of such approach-avoidance training effects are discussed.

Development and validation of the ambiguous scenario task for perfectionistic concerns for university students.

BACKGROUND AND OBJECTIVES: Interpretation biases (IBs) are found in a range of psychological disorders, and the transdiagnostic role of IBs has gained increasing attention. Among the variants, IBs of perfectionism (e.g., interpreting a trivial error as equivalent to complete failure) are understood to be a central transdiagnostic phenotype. Perfectionism is a multidimensional construct and the dimension of perfectionistic concerns has been found to be most closely related to psychopathology. Therefore, capturing IBs that are specifically related to perfectionistic concerns (not perfectionism in general) is of particular importance in studying pathological IBs. Thus, we developed and validated the Ambiguous Scenario Task for Perfectionistic Concerns (AST-PC) to be used in university students. METHODS: We created two versions of the AST-PC and administered each version to one of two independent student samples (i.e., Version A to n = 108 and Version B to n = 110). We then examined the factor structure and associations with established questionnaires of perfectionism, depression, and anxiety. RESULTS: The AST-PC showed good factorial validity, confirming the hypothesized three-factor structure: perfectionistic concerns, adaptive, and maladaptive (but not perfectionistic) interpretations. The interpretations related to perfectionistic concerns showed good correlations with questionnaires of perfectionistic concerns, depressive symptoms, and trait anxiety. LIMITATIONS: Additional validation studies are required to establish the temporal stability of the task scores and their sensitivity to experimental induction and clinical intervention. Additionally, IBs of perfectionism should be investigated within a broader transdiagnostic context. CONCLUSIONS: The AST-PC demonstrated good psychometric properties. Future applications of the task are discussed.

Conscious knowledge of CS-UCS contingency information affects extinction retrieval of conditioned disgust responses: Findings from an online de novo disgust conditioning task.

Objective: The present study aimed to establish and develop an online de novo conditioning paradigm for the measurement of conditioned disgust responses. We further explored the effects of explicit instructions about the CS-UCS contingency on extinction learning and retrieval of conditioned disgust responses. Method: The study included a sample of 115 healthy participants. Geometric figures served as conditioned stimuli (CS) and disgust-evoking pictures as unconditioned stimuli (UCS). During disgust conditioning, the CS+ was paired with the UCS (66% reinforcement) and the CS- remained unpaired; during extinction and retrieval, no UCS was presented. Half of the participants (n = 54) received instructions prior to the disgust extinction stating that the UCS will not be presented anymore. 1-2 days or 7-8 days later participants performed a retrieval test. CS-UCS contingency, disgust and valence ratings were used as dependent measures. Results: Successful acquisition of conditioned disgust response was observed on the level of CS-UCS contingency, disgust and valence ratings. While some decline in valence and disgust ratings during the extinction stage was observed, contingency instructions did not significantly affect extinction performance. Retrieval one week later revealed that contingency instructions increased the discrimination of the CSs. Conclusions: Extinction of conditioned disgust responses is not affected by explicit knowledge of the CS-UCS contingencies. However, contingency instructions prior to extinction seem to have a detrimental effect on long-term extinction retrieval.

Effects of Training Body-Related Interpretations on Panic-Related Cognitions and Symptoms.

Background: Interpretation biases (IBs) are central in panic disorder, and there is rich evidence showing that these are correlated with and predictive of panic-relevant symptomatology. However, experimental studies are needed to examine the potential causal effects of IBs, as predicted by cognitive models. Methods: Panic-related IBs were manipulated via a sentence-completion Cognitive Bias Modification-Interpretation (CBM-I) training. The sample included N = 112 healthy participants reporting moderate levels of fear of bodily sensations. Participants were randomly allocated to a positive, negative, or control CBM-I condition. To test the trainings' effect on panic-relevant cognitive processing, IBs were assessed via proximal and distal measures. Symptom provocation tasks were applied to test transfer to panic-relevant symptomatology. Results: Results on the proximal measure showed that positive CBM-I led to more positive IBs compared to negative, and control training. Further, positive CBM-I led to more positive IBs on the distal measure as compared to negative CBM-I. However, there were no differential training effects on panic-related symptomatology triggered via the provocation tasks. Conclusion: The findings indicate a limited generalization of the effects of CBM-I on IBs and panic-related symptoms. Potential means to improve generalization, such as applying more nuanced measures and combining CBM-I with psychoeducation are discussed.

To sleep or not to sleep, that is the question: A systematic review and meta-analysis on the effect of post-trauma sleep on intrusive memories of analog trauma.

Distressing intrusive memories of a traumatic event are one of the hallmark symptoms of posttraumatic stress disorder. Thus, it is crucial to identify early interventions that prevent the occurrence of intrusive memories. Both, sleep and sleep deprivation have been discussed as such interventions, yet previous studies yielded contradicting effects. Our systematic review aims at evaluating existing evidence by means of traditional and individual participant data (IPD) meta-analyses to overcome power issues of sleep research. Until May 16th, 2022, six databases were searched for experimental analog studies examining the effect of post-trauma sleep versus wakefulness on intrusive memories. Nine studies were included in our traditional meta-analysis (8 in the IPD meta-analysis). Our analysis provided evidence for a small effect favoring sleep over wakefulness, log-ROM = 0.25, p < .001, suggesting that sleep is associated with a lower number of intrusions but unrelated to the occurrence of any versus no intrusions. We found no evidence for an effect of sleep on intrusion distress. Heterogeneity was low and certainty of evidence for our primary analysis was moderate. Our findings suggest that post-trauma sleep has the potential to be protective by reducing intrusion frequency. More research is needed to determine the impact following real-world trauma and the potential clinical significance.

The Good, the Bad, and the Ugly-Chances, Challenges, and Clinical Implications of Avoidance Research in Psychosomatic Medicine.

Avoidance behaviors are shaped by associative learning processes in response to fear of impending threats, particularly physical harm. As part of a defensive repertoire, avoidance is highly adaptive in case of acute danger, serving a potent protective function. However, persistent or excessive fear and maladaptive avoidance are considered key factors in the etiology and pathophysiology of anxiety- and stress-related psychosomatic disorders. In these overlapping conditions, avoidance can increase the risk of mental comorbidities and interfere with the efficacy of cognitive behavioral treatment approaches built on fear extinction. Despite resurging interest in avoidance research also in the context of psychosomatic medicine, especially in conditions associated with pain, disturbed interoception, and disorders of the gut-brain axis, current study designs and their translation into the clinical context face significant challenges limiting both, the investigation of mechanisms involved in avoidance and the development of novel targeted treatment options. We herein selectively review the conceptual framework of learning and memory processes, emphasizing how classical and operant conditioning, fear extinction, and return of fear shape avoidance behaviors. We further discuss pathological avoidance and safety behaviors as hallmark features in psychosomatic diseases, with a focus on anxiety- and stress-related disorders. Aiming to emphasize chances of improved translational knowledge across clinical conditions, we further point out limitations in current experimental avoidance research. Based on these considerations, we propose means to improve existing avoidance paradigms to broaden our understanding of underlying mechanisms, moderators and mediators of avoidance, and to inspire tailored treatments for patients suffering from psychosomatic disorders.

Scrambled but valid? The scrambled sentences task as a measure of interpretation biases in psychopathology: A systematic review and meta-analysis.

The Scrambled Sentences Task (SST) is frequently used to assess interpretation biases (IBs). However, neither the range of its applications nor the quality of the empirical evidence it provides has been systematically examined. This systematic review investigates the types of samples and disorders in which the SST has been applied and evaluates its psychometric properties via a meta-analysis. The databases PubMed and EBSCOhost (including PsycINFO, PsycARTICLES, PSYNDEX, MEDLINE) were examined (last search: September 2021) and 93 studies from 91 manuscripts were included. Results showed that the SST has been applied predominantly in unselected samples or those with elevated levels of subsyndromal symptoms, with about a third of the studies employing the SST in a clinical population. While the SST was initially developed to assess depression-related IBs, it has now been extended to other disorders, in particular anxiety disorders. Results of the meta-analyses indicated good convergent validity and reliability across disorders, albeit in the context of substantial heterogeneity. Findings concerning divergent validity were mixed with high correlations across disorders between the SST and trait anxiety in particular, questioning its specificity. Future research should consider developing standardized SST versions and investigating its relationships with other measures of IB.

Measuring thinspiration and fear of fat indirectly. A matter of approach and avoidance.

The concepts thinspiration and fear of fat are crucial regarding the development and maintenance of body image disturbances and eating pathology. This study aimed to advance our current understanding of these two motivational concepts. Unlike previous studies that have primarily relied on self report measures to investigate thinspiration and fear of fat, we applied an indirect measure, namely a Stimulus Response Compatibility (SRC) task. During our SRC task, undergraduate female students were instructed to symbolically approach and avoid pictures of thin and chubby models. Hence, the participants' reaction times during the SRC task provided an index of the automatic affective and motivational valence of the models. Results showed that participants were faster to approach than to avoid thin models, however, there was no difference in approach-avoidance responses regarding chubby models. Analyses revealed that the approach-avoidance responses were related to important eating-related, cognitive schemata, e.g., the participants' level of drive for thinness, thin-ideal internalization, body dissatisfaction and their weight control behaviors. These findings clearly support the application of an indirect measure such as the SRC task in order to examine the concepts thinspiration and fear of fat, and highlight the need for further research that validates and extends current results.