Optimizing Outcomes in Psychotherapy for Anxiety Disorders Using Smartphone-Based and Passive Sensing Features: Protocol for a Randomized Controlled Trial.

BACKGROUND: Psychotherapies, such as cognitive behavioral therapy (CBT), currently have the strongest evidence of durable symptom changes for most psychological disorders, such as anxiety disorders. Nevertheless, only about half of individuals treated with CBT benefit from it. Predictive algorithms, including digital assessments and passive sensing features, could better identify patients who would benefit from CBT, and thus, improve treatment choices. OBJECTIVE: This study aims to establish predictive features that forecast responses to transdiagnostic CBT in anxiety disorders and to investigate key mechanisms underlying treatment responses. METHODS: This study is a 2-armed randomized controlled clinical trial. We include patients with anxiety disorders who are randomized to either a transdiagnostic CBT group or a waitlist (referred to as WAIT). We index key features to predict responses prior to starting treatment using subjective self-report questionnaires, experimental tasks, biological samples, ecological momentary assessments, activity tracking, and smartphone-based passive sensing to derive a multimodal feature set for predictive modeling. Additional assessments take place weekly at mid- and posttreatment and at 6- and 12-month follow-ups to index anxiety and depression symptom severity. We aim to include 150 patients, randomized to CBT versus WAIT at a 3:1 ratio. The data set will be subject to full feature and important features selected by minimal redundancy and maximal relevance feature selection and then fed into machine leaning models, including eXtreme gradient boosting, pattern recognition network, and k-nearest neighbors to forecast treatment response. The performance of the developed models will be evaluated. In addition to predictive modeling, we will test specific mechanistic hypotheses (eg, association between self-efficacy, daily symptoms obtained using ecological momentary assessments, and treatment response) to elucidate mechanisms underlying treatment response. RESULTS: The trial is now completed. It was approved by the Cantonal Ethics Committee, Zurich. The results will be disseminated through publications in scientific peer-reviewed journals and conference presentations. CONCLUSIONS: The aim of this trial is to improve current CBT treatment by precise forecasting of treatment response and by understanding and potentially augmenting underpinning mechanisms and personalizing treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03945617; https://clinicaltrials.gov/ct2/show/results/NCT03945617. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42547.

Understanding heterogeneity, comorbidity, and variability in depression: Idiographic models and depression outcomes.

This study uses time-intensive, item-level assessment to examine individual depressive and co-occurring symptom dynamics. Participants experiencing moderate-severe depression (N = 31) completed ecological momentary assessment (EMA) four times per day for 20 days (total observations = 2480). We estimated idiographic networks using MDD, anxiety, and ED items. ED items were most frequently included in individual networks relative to depression and anxiety items. We built ridge and logistic regression ensembles to explore how idiographic network centrality metrics performed at predicting between-subject depression outcomes (PHQ-9 change score and clinical deterioration, respectively) at 6-months follow-up. For predicting PHQ-9 change score, R2 ranged between 0.13 and 0.28. Models predicting clinical deterioration ranged from no better than chance to 80 % accuracy. This pilot study shows how co-occurring anxiety and ED symptoms may contribute to the maintenance of depressive symptoms. Future work should assess the predictive utility of psychological networks to develop understanding of how idiographic models may inform clinical decisions.

Racial and Ethnic Inequities at the Practice and Physician Levels in Timely Next-Generation Sequencing for Patients With Advanced Non-Small-Cell Lung Cancer Treated in the US Community Setting.

PURPOSE: Racial/ethnic inequities in next-generation sequencing (NGS) were examined for patients with advanced non-small-cell lung cancer (aNSCLC) at the practice and physician levels to inform policies to improve equitable quality of care. METHODS: This retrospective study used a nationwide electronic health record-derived deidentified database for patients with aNSCLC diagnosed between April 2018 and March 2022 in the community setting. Timely NGS was an NGS result between initial diagnosis and ≤60 days after advanced diagnosis. We studied how inequities were driven by (1) non-Latinx Black (Black) and Latinx patient under-representation at high testing practices versus (2) Black and Latinx patients being tested at lower rates than non-Latinx White (White) patients, even at the same practice. We defined these two concepts as across inequity and within inequity, respectively, with total inequity as their summation. Mean percentage point inequities were estimated using a Bayesian approach. RESULTS: A total of 12,045 patients (9,981 White; 1,528 Black; 536 Latinx) met study criteria. At the practice level, versus White patients, the mean percentage point difference in NGS testing total inequity was 7.49 for Black and 8.26 for Latinx. Within- and across-practice inequities contributed to total inequity in NGS testing for Black (48% v 52%) and Latinx patients (60% v 40%). At the physician level, versus White patients, the mean percentage point difference in total inequity was 7.73 for Black and 8.81 for Latinx patients. Within- versus across-physician inequities contributed to total inequity for Black and Latinx patients (77% v 23% and 67% v 33%). CONCLUSION: Within-practice, across-practice, and across-physician inequities were main contributors to total inequity in NGS testing, requiring a suite of interventions to effectively address inequities.

Online false discovery rate control for LORD++ and SAFFRON under positive, local dependence.

Online testing procedures assume that hypotheses are observed in sequence, and allow the significance thresholds for upcoming tests to depend on the test statistics observed so far. Some of the most popular online methods include alpha investing, LORD++, and SAFFRON. These three methods have been shown to provide online control of the "modified" false discovery rate (mFDR) under a condition known as CS. However, to our knowledge, LORD++ and SAFFRON have only been shown to control the traditional false discovery rate (FDR) under an independence condition on the test statistics. Our work bolsters these results by showing that SAFFRON and LORD++ additionally ensure online control of the FDR under a "local" form of nonnegative dependence. Further, FDR control is maintained under certain types of adaptive stopping rules, such as stopping after a certain number of rejections have been observed. Because alpha investing can be recovered as a special case of the SAFFRON framework, our results immediately apply to alpha investing as well. In the process of deriving these results, we also formally characterize how the conditional super-uniformity assumption implicitly limits the allowed p-value dependencies. This implicit limitation is important not only to our proposed FDR result, but also to many existing mFDR results.

Bedtime regularity predicts positive affect among veterans with posttraumatic stress disorder: an ecological momentary assessment study.

BACKGROUND: Regularizing bedtime and out-of-bed times is a core component of behavioral treatments for sleep disturbances common among patients with posttraumatic stress disorder (PTSD). Although improvements in subjective sleep complaints often accompany improvements in PTSD symptoms, the underlying mechanism for this relationship remains unclear. Given that night-to-night sleep variability is a predictor of physical and mental well-being, the present study sought to evaluate the effects of bedtime and out-of-bed time variability on daytime affect and explore the optimal window lengths of over which variability is calculated. METHODS: For about 30 days, male U.S. military veterans with PTSD (N = 64) in a residential treatment program provided ecological momentary assessment data on their affect and slept on beds equipped with mattress actigraphy. We computed bedtime and out-of-bed time variability indices with varying windows of days. We then constructed multilevel models to account for the nested structure of our data and evaluate the impact of bedtime and out-of-bed time variability on daytime affect. RESULTS: More regular bedtime across 6-9 days was associated with greater subsequent positive affect. No similar effects were observed between out-of-bed time variability and affect. CONCLUSIONS: Multiple facets of sleep have been shown to differently predict daily affect, and bedtime regularity might represent one of such indices associated with positive, but not negative, affect. A better understanding of such differential effects of facets of sleep on affect will help further elucidate the complex and intertwined relationship between sleep and psychopathology. TRIAL REGISTRATION: The trial retrospectively was registered on the Defense Technical Information Center website: Award # W81XWH-15-2-0005.

Elevated emotion network connectivity is associated with fluctuations in depression.

Elevated emotion network connectivity is thought to leave people vulnerable to become and stay depressed. The mechanism through which this arises is however unclear. Here, we test the idea that the connectivity of emotion networks is associated with more extreme fluctuations in depression over time, rather than necessarily more severe depression. We gathered data from two independent samples of N = 155 paid students and N = 194 citizen scientists who rated their positive and negative emotions on a smartphone app twice a day and completed a weekly depression questionnaire for 8 wk. We constructed thousands of personalized emotion networks for each participant and tested whether connectivity was associated with severity of depression or its variance over 8 wk. Network connectivity was positively associated with baseline depression severity in citizen scientists, but not paid students. In contrast, 8-wk variance of depression was correlated with network connectivity in both samples. When controlling for depression variance, the association between connectivity and baseline depression severity in citizen scientists was no longer significant. We replicated these findings in an independent community sample (N = 519). We conclude that elevated network connectivity is associated with greater variability in depression symptoms. This variability only translates into increased severity in samples where depression is on average low and positively skewed, causing mean and variance to be more strongly correlated. These findings, although correlational, suggest that while emotional network connectivity could predispose individuals to severe depression, it could also be leveraged to bring about therapeutic improvements.

Sleep Quality Moderates the Relationship Between Daily Mean Levels and Variability of Positive Affect.

Despite the well-established bidirectional association between sleep and daytime affect, most studies examining this relationship have focused on mean levels of affect. However, research solely focusing on mean levels of affect inherently neglects variability in affect, which has been shown to predict both psychological and physical well-being beyond mean levels. The present study assessed sleep quality and daytime affect using ecological momentary assessment in a combined sample of individuals (N = 80; 8,881 observations) with and without anxiety and mood disorders. Results from the present study partially replicated extant work on the negative association between negative affect (NA) variability and subsequent sleep quality. Furthermore, less satisfying sleep amplified the positive relationship between daily mean levels and variability of positive affect (PA). The results did not differ by clinical status. The present study offers novel evidence suggesting that previous night's sleep quality influences the stability of varying daily levels of PA. Uncovering the dynamics of sleep and affect beyond mean levels will help further elucidate mechanisms linking sleep and subsequent affective experiences.

Clinician Opinions: Perceived Utility of and Barriers to Incorporating Pretreatment Ecological Momentary Assessment Into Clinical Care.

Increasingly, clinicians have the option of including technological components into clinical care. However, little research has assessed clinicians' interest in utilizing technology in their clinical work. Here, clinicians reported their opinions related to using a mobile assessment platform (MAP) to collect ecological data from clients before providing clinical care. Practicing and training mental health clinicians (N = 221) reported demographics, characteristics of their clinical work, and confidence in their clinical skill. Participants then read a description of MAP and responded to questions about their perceived benefits of and barriers to its use. Last, participants rated their interest in using MAP in their clinical work. These perceptions were then factor-analyzed and the resulting factor scores were regressed onto clinician characteristics. Interest in using MAP was significantly lower for the group that endorsed a psychodynamic/psychoanalytic orientation and those with greater confidence in their clinical skills. Across scales, we found a pattern that participants who did not identify as male, those with a psychodynamic/psychoanalytic orientation, and those with greater confidence in their clinical skills tended to have lower ratings of the benefits of and higher ratings for the barriers to using MAP. Results revealed that significant differences in opinions about incorporating technology into clinical work exist between different groups of clinicians. This information may be useful in future work that attempts to implement technological tools into clinical settings.

Examining the Concurrent and Predictive Validity of Single Items in Ecological Momentary Assessments.

Although single items can save time and burden in psychology research, concerns about their reliability have made the use of multiple-item measures the default standard practice. Although single items cannot demonstrate internal reliability, their criterion validity can be compared with multiple-item measures. Using ecological momentary assessment data, we evaluated repeated measures correlations and constructed multilevel cross-lagged models to assess concurrent and predictive validity of single- and multiple-item measures. Correlations between the single- and multiple-item measures ranged from .24 to .61. In 27 of 29 unique single-item predictor models, single items demonstrated significant predictive validity, and in one of eight sets of comparisons, a single-item predictor exhibited a larger effect size than its multiple-item counterpart. Although multiple-item measures generally performed better than single items, the added benefit of multiple items was modest in most cases. The present data provide support for the use of single-item measures in intensive longitudinal designs.

The Hierarchical Taxonomy of Psychopathology (HiTOP) Is Not an Improvement Over the DSM.

In their response to our article (both in this issue), DeYoung and colleagues did not sufficiently address three fundamental flaws with the Hierarchical Taxonomy of Psychopathology (HiTOP). First, HiTOP was created using a simple-structure factor-analytic approach, which does not adequately represent the dimensional space of the symptoms of psychopathology. Consequently, HiTOP is not the empirical structure of psychopathology. Second, factor analysis and dimensional ratings do not fix the problems inherent to descriptive (folk) classification; self-reported symptoms are still the basis on which clinical judgments about people are made. Finally, HiTOP is not ready to use in real-world clinical settings. There is currently no empirical evidence demonstrating that clinicians who use HiTOP have better clinical outcomes than those who use the Diagnostic and Statistical Manual of Mental Disorders (DSM). In sum, HiTOP is a factor-analytic variation of the DSM that does not get the field closer to a more valid and useful taxonomy.

Identifying and predicting posttraumatic stress symptom states in adults with posttraumatic stress disorder.

Between-person heterogeneity of posttraumatic stress disorder (PTSD) is well established. Within-person analyses and the DSM-5 suggest that heterogeneity may also be evident within individuals across time as they move through social contexts and biological cycles. Modeling within-person symptom-level fluctuations may confirm such heterogeneity, elucidate mechanisms of disorder maintenance, and inform time- and person-specific interventions. The present study aimed to identify and predict discrete within-person disorder presentations, or symptom states, and explore group-level patterns of these states. Adults (N = 20, 60.0% male, M age = 38.25 years) with PTSD responded to symptom surveys four times per day for 30 days. We subjected each individual's dataset to Gaussian finite mixture modeling (GFMM) to uncover latent, within-person classes of symptom levels (i.e., states) and predicted those states with idiographic elastic net regularized regression using a set of time-based and behavioral predictors. Next, we conducted a GFMM of the within-person GFMM outputs and tested idiographic prediction models of these states. Multiple within-person states were revealed for 19 of 20 participants (Mdn = 4; 66 for the full sample). Prediction models were moderately successful, M AUC = .66 (d = 0.58), range: .50-1.00. The GFMM of the within-person model outputs revealed two states: one with above-average and one with below-average symptom levels. Prediction models were, again, moderately successful, M AUC = .66; range: .50-.89. The findings provide evidence for within-person heterogeneity of PTSD as well as between-person similarities and suggest that future work should incorporate additional contextual variables as symptom state predictors.

Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis.

BACKGROUND: The role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis. METHODS: We searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models. RESULTS: Six observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I2 = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02). CONCLUSIONS: Evidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.

Unsupervised clustering of autonomic temporal networks in clinically distressed and psychologically healthy individuals.

The present study recruited psychologically healthy individuals and individuals with clinically-severe Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnoses, including generalized anxiety disorder, major depressive disorder, social anxiety disorder, posttraumatic stress disorder, panic disorder, persistent depressive disorder, and specific phobia. During the course of a structured clinical interview, 200 individuals provided continuous electrocardiogram and impedance cardiography data. Of these N = 150 were used for exploratory analyses and N = 50 for confirmatory analyses. From these time series, we modeled heart period (i.e. interbeat interval), pre-ejection period, respiratory sinus arrhythmia, and respiration rate. The group iterative multiple model estimation (GIMME) model was used to generate group and individual-level network models which, in turn, were used to conduct unsupervised classification of individual-level models into subgroups. Four subgroups were identified, comprising N = 22, N = 25, N = 26, and N = 61 individuals, with an additional 16 individuals left unclassified. The subgroup models were then used to estimate directed network models, from which out-degree and in-degree centrality were estimated for each group. Two groups, Group 2 and Group 4 exhibited elevated symptoms of depression and anxiety relative to the remaining sample. However, only one of these, Group 2, exhibited additional physiological risk features, including a significantly elevated average heart rate, and significantly reduced parasympathetic regulation (measured via respiratory sinus arrhythmia). We discuss the implications for utilizing network models for conducting systems-level analyses of physiological systems in clinically-distressed and psychologically healthy individuals.

Folk Classification and Factor Rotations: Whales, Sharks, and the Problems With the Hierarchical Taxonomy of Psychopathology (HiTOP).

The Hierarchical Taxonomy of Psychopathology (HiTOP) uses factor analysis to group people with similar self-reported symptoms (i.e., like-goes-with-like). It is hailed as a significant improvement over other diagnostic taxonomies. However, the purported advantages and fundamental assumptions of HiTOP have received little, if any scientific scrutiny. We critically evaluated five fundamental claims about HiTOP. We conclude that HiTOP does not demonstrate a high degree of verisimilitude and has the potential to hinder progress on understanding the etiology of psychopathology. It does not lend itself to theory-building or taxonomic evolution, and it cannot account for multifinality, equifinality, or developmental and etiological processes. In its current form, HiTOP is not ready to use in clinical settings and may result in algorithmic bias against underrepresented groups. We recommend a bifurcation strategy moving forward in which the DSM is used in clinical settings while researchers focus on developing a falsifiable theory-based classification system.

Pooled and person-specific machine learning models for predicting future alcohol consumption, craving, and wanting to drink: A demonstration of parallel utility.

BACKGROUND AND AIMS: The specific factors driving alcohol consumption, craving, and wanting to drink, are likely different for different people. The present study sought to apply statistical classification methods to idiographic time series data in order to identify person-specific predictors of future drinking-relevant behavior, affect, and cognitions in a college student sample. DESIGN: Participants were sent 8 mobile phone surveys per day for 15 days. Each survey assessed the number of drinks consumed since the previous survey, as well as positive affect, negative affect, alcohol craving, drinking expectancies, perceived alcohol consumption norms, impulsivity, and social and situational context. Each individual's data were split into training and testing sets, so that trained models could be validated using person-specific out-of-sample data. Elastic net regularization was used to select a subset of a set of 40 variables to be used to predict either alcohol consumption, craving, or wanting to drink, forward in time. SETTING: A west-coast university. PARTICIPANTS: Thirty-three university students who had consumed alcohol in their lifetime. MEASUREMENTS: Mobile phone surveys. FINDINGS: Averaging across participants, accurate out-of-sample predictions of future drinking were made 76% of the time. For craving, the mean out-of-sample R² value was .27. For wanting to drink, the mean out-of-sample R² value was .27. CONCLUSION: Using a person-specific constellation of psychosocial and temporal variables, it may be possible to accurately predict drinking behavior, affect, and cognitions before they occur. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Negative Emotion Differentiation Predicts Psychotherapy Outcome: Preliminary Findings.

Emotion differentiation (ED), the extent to which same-valenced emotions are experienced as distinct, is considered a valuable ability in various contexts owing to the essential affect-related information it provides. This information can help individuals understand and regulate their emotional and motivational states. In this study, we sought to examine the extent to which ED can be beneficial in psychotherapy context and specifically for predicting treatment response. Thirty-two prospective patients with mood and anxiety disorders completed four daily assessments of negative and positive emotions for 30 days before receiving cognitive-behavioral treatment. Depression, stress, and anxiety symptoms severity were assessed pre- and post-treatment using self-reports and clinical interviews. We conducted a series of hierarchical regression models in which symptoms change scores were predicted by ED while adjusting for the mean and variability. We found that negative ED was associated with greater self-reported treatment response (except for anxiety) when negative emotional variability (EV) was included in the models. Probing negative ED and EV's interactive effects suggested that negative ED was associated with greater treatment response (except for anxiety) for individuals with lower EV levels. Results were obtained while controlling for mean negative affect. Our findings suggest that negative ED can benefit psychotherapy patients whose negative emotions are relatively less variable. We discuss the meaning of suppression and interactive effects between affect dynamics and consider possible clinical implications.

Using mixed methods to construct and analyze a participatory agent-based model of a complex Zimbabwean agro-pastoral system.

Complex social-ecological systems can be difficult to study and manage. Simulation models can facilitate exploration of system behavior under novel conditions, and participatory modeling can involve stakeholders in developing appropriate management processes. Participatory modeling already typically involves qualitative structural validation of models with stakeholders, but with increased data and more sophisticated models, quantitative behavioral validation may be possible as well. In this study, we created a novel agent-based-model applied to a specific context: Zimbabwean non-governmental organization the Muonde Trust has been collecting data on their agro-pastoral system for the last 35 years and had concerns about land-use planning and the effectiveness of management interventions in the face of climate change. We collaboratively created an agent-based model of their system using their data archive, qualitatively calibrating it to the observed behavior of the real system without tuning any parameters to match specific quantitative outputs. We then behaviorally validated the model using quantitative community-based data and conducted a sensitivity analysis to determine the relative impact of underlying parameter assumptions, Indigenous management interventions, and different rainfall variation scenarios. We found that our process resulted in a model which was successfully structurally validated and sufficiently realistic to be useful for Muonde researchers as a discussion tool. The model was inconsistently behaviorally validated, however, with some model variables matching field data better than others. We observed increased model system instability due to increasing variability in underlying drivers (rainfall), and also due to management interventions that broke feedbacks between the components of the system. Interventions that smoothed year-to-year variation rather than exaggerating it tended to improve sustainability. The Muonde trust has used the model to successfully advocate to local leaders for changes in land-use planning policy that will increase the sustainability of their system.

Time to get personal? The impact of researchers choices on the selection of treatment targets using the experience sampling methodology.

OBJECTIVE: One of the promises of the experience sampling methodology (ESM) is that a statistical analysis of an individual's emotions, cognitions and behaviors in everyday-life could be used to identify relevant treatment targets. A requisite for clinical implementation is that outcomes of such person-specific time-series analyses are not wholly contingent on the researcher performing them. METHODS: To evaluate this, we crowdsourced the analysis of one individual patient's ESM data to 12 prominent research teams, asking them what symptom(s) they would advise the treating clinician to target in subsequent treatment. RESULTS: Variation was evident at different stages of the analysis, from preprocessing steps (e.g., variable selection, clustering, handling of missing data) to the type of statistics and rationale for selecting targets. Most teams did include a type of vector autoregressive model, examining relations between symptoms over time. Although most teams were confident their selected targets would provide useful information to the clinician, not one recommendation was similar: both the number (0-16) and nature of selected targets varied widely. CONCLUSION: This study makes transparent that the selection of treatment targets based on personalized models using ESM data is currently highly conditional on subjective analytical choices and highlights key conceptual and methodological issues that need to be addressed in moving towards clinical implementation.