Using the 'Leapfrog' Design as a Simple Form of Adaptive Platform Trial to Develop, Test, and Implement Treatment Personalization Methods in Routine Practice.

The route for the development, evaluation and dissemination of personalized psychological therapies is complex and challenging. In particular, the large sample sizes needed to provide adequately powered trials of newly-developed personalization approaches means that the traditional treatment development route is extremely inefficient. This paper outlines the promise of adaptive platform trials (APT) embedded within routine practice as a method to streamline development and testing of personalized psychological therapies, and close the gap to implementation in real-world settings. It focuses in particular on a recently-developed simplified APT design, the 'leapfrog' trial, illustrating via simulation how such a trial may proceed and the advantages it can bring, for example in terms of reduced sample sizes. Finally it discusses models of how such trials could be implemented in routine practice, including potential challenges and caveats, alongside a longer-term perspective on the development of personalized psychological treatments.

Positive mental imagery and mental health amongst university students in Pakistan.

Mental health problems amongst university students pose a major public health challenge, and this is particularly the case in Pakistan. Alongside broader societal and cultural pressures, cognitive factors likely also play a role in the development of and resilience to mental health problems and may provide a feasible target for interventions. The current study built on previous research in primarily European samples investigating the relationship between one cognitive factor, positive future-oriented mental imagery, and mental health, extending this to a sample of university students in Pakistan (N = 1838). In a cross-sectional design, higher vividness of positive future-oriented mental imagery was associated with lower levels of depressive symptoms and higher levels of positive mental health amongst participants completing questionnaire measures on paper (N = 1430) or online (N = 408). In the sample completing the measures on paper, these relationships remained statistically significant even when controlling for socio-demographic and mental health-related variables. The results provide a foundation for further investigating positive mental imagery as a potential mechanism of mental health and intervention target amongst university students in Pakistan.

Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment. Here we test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in primary health care will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition. METHODS: A total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU, but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (Antidepressant active comparison group). DISCUSSION: The clinical outcome of this study may help develop easily accessible, low-cost treatment of depression in primary health care. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long-term gain.

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.

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.

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.

A feasibility randomised controlled trial of a brief early intervention for adolescent depression that targets emotional mental images and memory specificity (IMAGINE).

Brief, evidence-based interventions for adolescent depression are urgently required, particularly for school-settings. Cognitive mechanisms research suggests dysfunctional mental imagery and overgeneral memory could be promising targets to improve mood. This feasibility randomised controlled trial with parallel symptomatic groups (n = 56) compared a novel imagery-based cognitive behavioural intervention (ICBI) to non-directive supportive therapy (NDST) in school settings. Blind assessments (of clinical symptoms and cognitive mechanisms) took place pre-intervention, post-intervention and follow-up three months later. The trial aimed to evaluate the feasibility and acceptability of the methodology and interventions, and estimate the likely range of effects of the intervention on self-reported depression. The pre-defined criteria for proceeding to a definitive RCT were met: full recruitment occurred within eleven months; retention was 89%; ICBI acceptability was above satisfactory; and no harm was indicated. Intention-to-treat analysis found large effects in favour of ICBI (relative to NDST) at post-intervention in reducing depressive symptoms (d = -1.34, 95% CI [-1.87, -0.80]) and improving memory specificity (d = 0.79 [0.35, 1.23]), a key cognitive target. The findings suggest that ICBI may not only improve mood but also strengthen abilities associated with imagining and planning the future, critical skills at this life stage. A fully powered evaluation of ICBI is warranted. Trial Registration: https://www.isrctn.com/; ISRCTN85369879.

Genes in treatment: Polygenic risk scores for different psychopathologies, neuroticism, educational attainment and IQ and the outcome of two different exposure-based fear treatments.

OBJECTIVES: Evidence for a genetic influence on psychological treatment outcome so far has been inconsistent, likely due to the focus on candidate genes and the heterogeneity of the disorders treated. Using polygenic risk scores (PRS) in homogenous patient samples may increase the chance of detecting genetic influences. METHODS: A sample of 342 phobic patients treated either for clinically relevant dental fear (n = 189) or other (mixed) phobic fears (n = 153) underwent highly standardised exposure-based CBT. A brief five-session format was used to treat dental fear, whereas longer multi-session treatments were used with the mixed-fear cohort. PRS were calculated based on large genetic studies of Neuroticism, Educational Attainment (EA), Intelligence, and four psychopathology domains. We compared PRS of post-treatment and follow-up remitters and non-remitters and regressed PRS on fear reduction percentages. RESULTS: In the dental fear cohort, EA PRS were associated with treatment outcomes, i.e. drop-out, short- and long-term remission state, fear reduction, and attendance of subsequent dental appointments. In the mixed fear treatment cohort, no gene effects were observable. CONCLUSIONS: Results indicate the importance of EA-related traits for outcomes following brief, but not long, standardised exposure-based CBT. Such use of PRS may help inform selection and tailoring of treatments.

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).

Intranasal oxytocin increases state anhedonia following imagery training of positive social outcomes in individuals lower in extraversion, trust-altruism, and openness to experience.

Psychological disorders such as major depressive disorder are characterised by interpersonal difficulties and anhedonia. A cognitive mechanism proposed to contribute to the maintenance of these problems is a diminished ability to generate positive mental imagery, especially regarding social interactions. The current study examined whether the effects of social imagery training on social activity and anhedonia could be enhanced with the addition of intranasal oxytocin, and whether these effects might be augmented in persons with a high propensity to engage socially (i.e., high extraversion). University students (N = 111) were randomised to self-administer intranasal oxytocin or placebo, followed by a single session of positive social or non-social imagery training that required participants to imagine 64 positive scenarios occurring in either a social or non-social context, respectively. There were no main effects of imagery type and drug, and no interaction effect on anhedonia and social activity, measured respectively via self-report and a behavioural task. Individuals low in extraversion, trust-altruism, and openness to experience reported significantly more anhedonia after receiving oxytocin relative to placebo, but only following imagery training of positive social outcomes. Results highlight the negative consequences of increasing oxytocin bioavailability after priming social contact in more withdrawn individuals.

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.

Cognitive Behavior Therapy at the Crossroads.

The early development of cognitive behavior therapy (CBT) can be characterized by the coming together of behavioral and cognitive traditions. However, the past decades have arguably seen more divergences than convergences within the field. The 9th World Congress of Behavioural and Cognitive Therapies was held in Berlin in July 2019 with the congress theme "CBT at the Crossroads." This title reflected in part the coming together of people from all over the world, but also the fact that recent developments raise important questions about the future of CBT, including whether we can in fact treat it as a unified field. In this paper, we briefly trace the history of CBT, then introduce a special issue featuring a series of articles exploring different aspects of the past, present, and future of CBT. Finally, we reflect on the possible routes ahead.

Mental health, suicidal ideation, and experience of bullying among university students in Pakistan.

This study investigates mental health, access to treatment, suicidality, and bullying among Pakistani university students. Data were collected from a sample of 355 university students in Pakistan. For reference, we compared these data to a sample previously collected from German and Chinese students. Results indicated relatively poorer mental health and access to mental health treatments among the Pakistani sample, including a higher rate of recent suicidal ideation and bullying. Acknowledgment of these issues in Pakistani culture would be a good starting point to work on developing solutions to enhance the overall mental health of Pakistani students.

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.

Targeting intrusive imagery using a competing task technique: a case study.

BACKGROUND: Even in cases with complexity, simple techniques can be useful to target a specific symptom. Intrusive mental images are highly disruptive, drive emotion, and contribute to maintaining psychopathology. Cognitive science suggests that we might target intrusive images using competing tasks. AIMS: We describe an imagery competing task technique within cognitive behavioural therapy (CBT) with a patient with bipolar disorder and post-traumatic stress disorder (PTSD) symptoms. The intervention - including Tetris computer game-play - was used (1) to target a specific image within one therapy session, and (2) to manage multiple images in daily life. METHOD: A single case (AB) design was used. (1) To target a specific image, the patient brought the image to mind and, after mental rotation instructions and game-play practice, played Tetris for 10 minutes. Outcomes, pre- and post-technique, were: vividness/distress ratings when the image was brought to mind; reported intrusion frequency over a week. (2) To manage multiple images, the patient used the intervention after an intrusive image occurred. Outcomes were weekly measures of: (a) imagery characteristics; (b) symptoms of PTSD, anxiety, depression and mania. RESULTS: (1) For the target image, there were reductions in vividness (80% to 40%), distress (70% to 0%), and intrusion frequency (daily to twice/week). (2) For multiple images, there were reductions from baseline to follow-up in (a) imagery vividness (38%), realness (66%) and compellingness (23%), and (b) PTSD symptoms (Impact of Events Scale-Revised score 26.33 to 4.83). CONCLUSION: This low-intensity intervention aiming to directly target intrusive mental imagery may offer an additional, complementary tool in CBT.

Psychometric properties of the German version of the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) in clinical routine settings: study design and protocol of a multitrait-multimethod study.

INTRODUCTION: The aim of this study is to investigate the diagnostic accuracy, psychometric properties and clinical utility of the German version of the Clinician-Administered Post-Traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) in routine clinical settings. METHODS AND ANALYSIS: This study is a non-interventional, multitrait-multimethod design, multicentre study that will be carried out at German civil and military inpatient and outpatient clinics. A total sample size of n=219 participants who have experienced at least one traumatic event according to criteria as defined in the DSM-5 will be recruited. For the investigation of the diagnostic accuracy and clinical utility of the CAPS-5, participants will be categorised into one of three groups, depending on their traumatic experiences and post-traumatic symptomatology: (1) monotraumatisation with PTSD; (2) multiple traumatisation with PTSD and (3) traumatisation without PTSD. Interviews will be conducted face to face by interviewers in routine clinical settings. All participants will also be asked to complete a comprehensive set of questionnaires in order to investigate different facets of construct validity and clinical utility. First, differences between all three groups in CAPS-5 sum and subscale scores will be investigated. Test-retest reliability and inter-rater reliability will be determined. Internal consistency will be calculated using structural equation modeling (SEM) based internal consistency coefficients. Construct validity will be measured with Spearman's rank correlation analyses and multivariate analyses of variance with Holm-Bonferroni corrected post hoc analysis of variances. In order to test diagnostic accuracy, receiver operating characteristics and sensitivity and specificity analyses will be conducted. The model structure of the German CAPS-5 will be analysed using confirmatory factor analyses. ETHICS AND DISSEMINATION: The study received ethical approval by the Ethics Committees of the Faculty of Psychology at the Ruhr-Universität Bochum (reference numbers: 331 and 358). The results of the study will be presented nationally and internationally at scientific conferences and will be published in scientific journals. TRIAL REGISTRATION NUMBER: DRKS00015325.

Effect of an upright (vs. stooped) posture on interpretation bias, imagery, and emotions.

BACKGROUND AND OBJECTIVES: Adopting an upright (vs. stooped) posture has been related to positive effects on emotional and cognitive processes. However, there is no evidence concerning the effect of posture on two key processes associated with the maintenance of depression: interpretation bias and vividness of mental imagery. The objectives were to investigate the effect of adopting an upright (vs. stooped) posture on interpretation bias and vividness of positive and negative mental imagery, and to explore the interplay between these processes and depression-related emotions. METHODS: The sample consisted of 54 participants (Mage = 22.00, 64.8% women), who were randomly assigned to the upright or stooped condition. Participants answered self-report measures while they were adopting a specific posture. Posture was monitored through inertial technology. RESULTS: Main results were that: upright (vs. stooped) posture led to more positive interpretations of ambiguous information and increased positive emotions related to depression (happiness, optimism and vigor); time in an upright position was associated with change in interpretation bias and vividness of positive mental imagery; and level of depressive symptomatology moderated the effect of posture on the change in interpretation bias. LIMITATIONS: Limitations are related to the use of non-clinical sample, the use of short-term measurements, and the lack of an experimental condition adopting the usual posture. CONCLUSIONS: Posture interacts with mechanisms involved in the maintenance of depression, as well as with depression-related emotions. This study has clinical implications that should be continued explored in order to clarify the role of manipulating the posture in individuals with depressive symptomatology.