Developing an individualized treatment rule for Veterans with major depressive disorder using electronic health records.

Efforts to develop an individualized treatment rule (ITR) to optimize major depressive disorder (MDD) treatment with antidepressant medication (ADM), psychotherapy, or combined ADM-psychotherapy have been hampered by small samples, small predictor sets, and suboptimal analysis methods. Analyses of large administrative databases designed to approximate experiments followed iteratively by pragmatic trials hold promise for resolving these problems. The current report presents a proof-of-concept study using electronic health records (EHR) of n = 43,470 outpatients beginning MDD treatment in Veterans Health Administration Primary Care Mental Health Integration (PC-MHI) clinics, which offer access not only to ADMs but also psychotherapy and combined ADM-psychotherapy. EHR and geospatial databases were used to generate an extensive baseline predictor set (5,865 variables). The outcome was a composite measure of at least one serious negative event (suicide attempt, psychiatric emergency department visit, psychiatric hospitalization, suicide death) over the next 12 months. Best-practices methods were used to adjust for nonrandom treatment assignment and to estimate a preliminary ITR in a 70% training sample and to evaluate the ITR in the 30% test sample. Statistically significant aggregate variation was found in overall probability of the outcome related to baseline predictors (AU-ROC = 0.68, S.E. = 0.01), with test sample outcome prevalence of 32.6% among the 5% of patients having highest predicted risk compared to 7.1% in the remainder of the test sample. The ITR found that psychotherapy-only was the optimal treatment for 56.0% of patients (roughly 20% lower risk of the outcome than if receiving one of the other treatments) and that treatment type was unrelated to outcome risk among other patients. Change in aggregate treatment costs of implementing this ITR would be negligible, as 16.1% fewer patients would be prescribed ADMs and 2.9% more would receive psychotherapy. A pragmatic trial would be needed to confirm the accuracy of the ITR.

Is combined antidepressant medication (ADM) and psychotherapy better than either monotherapy at preventing suicide attempts and other psychiatric serious adverse events for depressed patients? A rare events meta-analysis.

Antidepressant medication (ADM)-only, psychotherapy-only, and their combination are the first-line treatment options for major depressive disorder (MDD). Previous meta-analyses of randomized controlled trials (RCTs) established that psychotherapy and combined treatment were superior to ADM-only for MDD treatment remission or response. The current meta-analysis extended previous ones by determining the comparative efficacy of ADM-only, psychotherapy-only, and combined treatment on suicide attempts and other serious psychiatric adverse events (i.e. psychiatric emergency department [ED] visit, psychiatric hospitalization, and/or suicide death; SAEs). Peto odds ratios (ORs) and their 95% confidence intervals were computed from the present random-effects meta-analysis. Thirty-four relevant RCTs were included. Psychotherapy-only was stronger than combined treatment (1.9% v. 3.7%; OR 1.96 [1.20-3.20], p = 0.012) and ADM-only (3.0% v. 5.6%; OR 0.45 [0.30-0.67], p = 0.001) in decreasing the likelihood of SAEs in the primary and trim-and-fill sensitivity analyses. Combined treatment was better than ADM-only in reducing the probability of SAEs (6.0% v. 8.7%; OR 0.74 [0.56-0.96], p = 0.029), but this comparative efficacy finding was non-significant in the sensitivity analyses. Subgroup analyses revealed the advantage of psychotherapy-only over combined treatment and ADM-only for reducing SAE risk among children and adolescents and the benefit of combined treatment over ADM-only among adults. Overall, psychotherapy and combined treatment outperformed ADM-only in reducing the likelihood of SAEs, perhaps by conferring strategies to enhance reasons for living. Plausibly, psychotherapy should be prioritized for high-risk youths and combined treatment for high-risk adults with MDD.

Treatment as a moderator and executive function as a mediator of the effect of a mindfulness ecological momentary intervention for generalized anxiety disorder.

BACKGROUND: Theory and research indicated that executive functioning (EF) correlated with, preceded, and stemmed from worry in generalized anxiety disorder (GAD). The present secondary analysis (Zainal & Newman, 2023b) thus determined whether EF domains mediated the effect of a 14-day (5 prompts/day) mindfulness ecological momentary intervention (MEMI) against a self-monitoring control (SM) for GAD. METHOD: Participants (N = 110) diagnosed with GAD completed self-reported (Attentional Control Scale, GAD Questionnaire, Perseverative Cognitions Questionnaire) and performance-based tests (Letter-Number Sequencing, Stroop, Trail Making Test-B, Verbal Fluency) at baseline, post-treatment, and one-month follow-up (1MFU). Causal mediation analyses determined if pre-post changes in EF domains preceded and mediated the effect of MEMI against SM on pre-1MFU changes in GAD severity and trait repetitive negative thinking (RNT). RESULTS: MEMI was more efficacious than SM in improving pre-post inhibition (ß = -2.075, 95% [-3.388, -0.762], p = .002), working memory (ß = 0.512, 95% [0.012, 1.011], p = .045), and set-shifting (ß = -2.916, 95% [-5.142, -0.691], p = .010) but not verbal fluency and attentional control. Within groups, MEMI but not SM produced improvements in all examined pre-post EF outcomes except attentional control. Only pre-post improvements in inhibition mediated the effect of MEMI against SM on pre-1MFU reductions in GAD severity (ß = -0.605, 95% [-1.357, -0.044], p = .030; proportion mediated = 7.1%) and trait RNT (ß = -0.024, 95% [-0.054, -0.001], p = .040; proportion mediated = 7.4%). These patterns remained after conducting sensitivity analyses with non-linear mediator-outcome relations. CONCLUSIONS: Optimizing MEMI for GAD might entail specifically boosting inhibition plausibly by augmenting it with dialectical behavioral therapy, encouraging high-intensity physical exercises, and targeting negative emotional contrast avoidance.

Prospective network analysis of proinflammatory proteins, lipid markers, and depression components in midlife community women.

BACKGROUND: Vulnerability theories propose that suboptimal levels of lipid markers and proinflammatory proteins predict future heightened depression. Scar models posit the reverse association. However, most studies that tested relationships between non-specific immune/endocrine markers and depression did not separate temporal inferences between people and within-person and how different immunometabolism markers related to unique depression symptoms. We thus used cross-lagged prospective network analyses (CLPN) to investigate this topic. METHODS: Community midlife women (n = 2224) completed the Center for Epidemiologic Studies-Depression scale and provided biomarker samples across five time-points spanning 9 years. CLPN identified significant relations (edges) among components (nodes) of depression (depressed mood, somatic symptoms, interpersonal issues), lipid markers [insulin, fasting glucose, triglycerides, low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL)], and proinflammatory proteins [C-reactive protein (CRP), fibrinogen], within and across time-points. All models adjusted for age, estradiol, follicle-stimulating hormone, and menopausal status. RESULTS: In within-person temporal networks, higher CRP and HDL predicted all three depression components (d = 0.131-2.112). Increased LDL preceded higher depressed mood and interpersonal issues (v. somatic symptoms) (d = 0.251-0.327). Elevated triglycerides predicted more somatic symptoms (v. depressed mood and interpersonal problems) (d = 0.131). More interpersonal problems forecasted elevated fibrinogen and LDL levels (d = 0.129-0.331), and stronger somatic symptoms preceded higher fibrinogen levels (d = 0.188). CONCLUSIONS: Results supported both vulnerability and scar models. Long-term dysregulated immunometabolism systems, social disengagement, and related patterns are possible mechanistic accounts. Cognitive-behavioral therapies that optimize nutrition and physical activity may effectively target depression.

A cross-lagged prospective network analysis of depression and anxiety and cognitive functioning components in midlife community adult women.

BACKGROUND: Scar theory proposes that heightened depression and anxiety precede and predict worse cognitive functioning outcomes, whereas the vulnerability theory posits the opposite pathway. However, most investigations on this topic have been cross-sectional, precluding causal inferences. Thus, we used cross-lagged prospective network analyses to facilitate causal inferences in understanding the relations between psychopathology and cognitive functioning components. METHODS: Racially-diverse midlife women (n = 1816) participated in the Study of Women's Health Across the Nation at two time-points, spanning one year apart. Five psychopathology (anxiety severity, depressed mood, somatic symptoms, positive affect, interpersonal problems) and four cognitive functioning nodes (working memory (WM), processing speed (PS), facial recognition (FCR), and verbal memory (VRM)) were assessed. All analyses adjusted for age, menopausal status, estradiol, and follicle-stimulating hormones. RESULTS: Contemporaneous networks yielded notable inverse between-node relations (edges) between interpersonal problems and reduced FCR and PS, and between depressed mood and lower FCR, VRM, or PS. Nodes that had the highest likelihood to bridge other constructs were positive affect, anxiety severity, WM, and VRM. Temporal networks produced edges consistent with the scar (v. vulnerability) hypotheses. Higher somatic symptoms were related to reduced PS and WM, and greater depressed mood was correlated with lower future PS and WM. Also, higher anxiety severity coincided with decreased future PS and WM. Greater positive affect was associated with stronger future PS, FCR, and WM. Also, positive affect had the strongest relations with other nodes. CONCLUSIONS: Findings suggest the importance of targeting symptoms and cognitive functioning simultaneously.

Development of a model to predict antidepressant treatment response for depression among Veterans.

BACKGROUND: Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA). METHODS: A 2018-2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample. RESULTS: In total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors. CONCLUSIONS: Although these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.

Longitudinal associations between academic competence-building and depression symptoms in early adolescence.

The longitudinal associations between academic competence-building and depression symptoms were investigated among 741 early adolescents in Singapore. Extending from past studies on academic achievement and depression, the current research tested two competing hypotheses - the academic incompetence hypothesis versus the adjustment erosion hypothesis using a 3-wave longitudinal study over an academic year. The former hypothesis suggests that prior deficits in academic competence-building lead to subsequent depression symptoms, whereas the latter posits that previous depression leads to subsequent deficits in competence-building. Longitudinal associations between a higher-order competence-building factor (operationalized using multiple constituent motivational variables) and depression were examined using a random intercept cross-lagged panel model. Results indicated that within-individual decreases in competence-building prospectively predicted subsequent within-individual increases in depression symptoms, but the opposite effect was not observed. Within-individual fluctuations in competence-building also predicted end-of-year grades and teacher-reported adjustment problems. Overall, the current findings were consistent with the academic incompetence hypothesis, suggesting that interventions aimed at sustaining academic competence-building could offer protection against the worsening of depression. These results clarified the within-individual developmental dynamics between academic competence-building and depression symptoms in adolescents over time.

Cognitive behavioral therapy (CBT) plus attention bias modification (ABM) reduces anxiety sensitivity and depressive symptoms in panic disorder: A pilot randomized trial.

BACKGROUND: Cognitive bias theories propose that reducing threat hypervigilance in mental disorders can augment cognitive behavioral therapy (CBT) outcomes. However, no studies have tested whether adding attention bias modification (ABM) can effectively enhance CBT's effects on anxiety sensitivity (AS), electromyography (EMG), and skin conductance (SC) for panic disorder (PD). This pilot randomized controlled trial (RCT) thus aimed to evaluate the efficacy of CBT + ABM (vs. CBT plus attention training placebo; PBO) on those outcomes. METHOD: This study is a secondary analysis (Baker et al., 2020). Adults with PD were randomized to receive CBT + ABM (n = 11) or CBT + PBO (n = 12). Before each of the first five CBT sessions, CBT + ABM and CBT + PBO participants completed a 15-min ABM task or attention training PBO, respectively. AS and depression severity as well as SC and EMG during habituation to a loud-tone startle paradigm were assessed. Hierarchical Bayesian analyses were conducted. RESULTS: During pre-post-treatment and pre-follow-up, CBM + ABM (vs. CBT + PBO) led to a notably greater reduction in ASI-Physical (between-group d = -1.26 to -1.25), ASI-Cognitive (d = -1.16 to -1.10), and depression severity (d = -1.23 to -0.99). However, no between-group difference was observed for ASI-Social, EMG, or SC indices. DISCUSSION: Adding a brief computerized ABM intervention to CBT for PD protocols may enhance therapeutic change.

Executive Functioning Constructs in Anxiety, Obsessive-Compulsive, Post-Traumatic Stress, and Related Disorders.

PURPOSE OF REVIEW: We synthesize theories proposing complex relations between cognitive functioning and anxiety-related concepts. We evaluate vulnerability theories suggesting that deficits in various cognitive functioning domains predict future anxiety-associated concepts. We examine scar theories asserting the opposite direction of effects (i.e., anxiety predicting cognitive dysfunction). Furthermore, we examine more novel frameworks on this topic. RECENT FINDINGS: Reliable evidence exists for the scar and vulnerability theories. This includes mounting data on diverse anxiety symptoms predicting cognitive dysfunction (and conversely) unfolding at between- and within-person levels (dynamic mutualism theory). It also includes data on the stronger effects or central influence of anxiety (versus non-anxiety) symptoms on executive functioning (EF; i.e., higher-order cognitive control governing myriad thinking and action repertoires) versus non-EF domains and vice versa (network theory). In addition, it reviews emerging evidence that enhanced cognitive control can correlate with higher anxiety among children (overgeneralized control theory). The generally inverse relations between anxiety symptoms and cognitive dysfunction are bidirectional and complex within and between persons. Plausible mediators and moderators merit more attention, including immune, metabolism, and neural markers and the social determinants of health.

Depression and worry symptoms predict future executive functioning impairment via inflammation.

BACKGROUND: Scar models posit that heightened anxiety and depression can increase the risk for subsequent reduced executive function (EF) through increased inflammation across months. However, the majority of past research on this subject used cross-sectional designs. We therefore examined if elevated generalized anxiety disorder (GAD), major depressive disorder (MDD), and panic disorder (PD) symptoms forecasted lower EF after 20 months through heightened inflammation. METHODS: Community-dwelling adults partook in this study (n = 614; MAGE = 51.80 years, 50% females). Time 1 (T1) symptom severity (Composite International Diagnostic Interview - Short Form), T2 (2 months after T1) inflammation serum levels (C-reactive protein, fibrinogen, interleukin-6), and T3 (20 months after T1) EF (Brief Test of Adult Cognition by Telephone) were assessed. Structural equation mediation modeling was performed. RESULTS: Greater T1 MDD and GAD (but not PD) severity predicted increased T2 inflammation (Cohen's d = 0.21-1.92). Moreover, heightened T2 inflammation forecasted lower T3 EF (d = -1.98 to -1.87). T2 inflammation explained 25-32% of the negative relations between T1 MDD or GAD and T3 EF. T1 GAD severity predicting T3 EF via T2 inflammation path was stronger among younger (v. older) adults. Direct effects of T1 MDD, GAD, and PD forecasting decreased T3 EF were found (d = -2.02 to -1.92). Results remained when controlling for socio-demographic, physical health, and lifestyle factors. CONCLUSIONS: Inflammation can function as a mechanism of the T1 MDD or GAD-T3 EF associations. Interventions that successfully treat depression, anxiety, and inflammation-linked disorders may avert EF decrements.

Within-person increase in pathological worry predicts future depletion of unique executive functioning domains.

BACKGROUND: Affective neuroscience and scar theories propose that increased excessive worry, the hallmark symptom of generalized anxiety disorder (GAD), predicts future declines in executive functioning (EF). However, the preponderance of cross-sectional designs used to examine between-person chronic worry-EF relationships has blocked progress on understanding their potentially causal within-person associations. Accordingly, this study used bivariate dual latent change score (LCS) models to test whether within-person increased GAD severity might relate to future reduced EF. METHODS: Community-dwelling adults (N = 2581, 46 years on average, s.d. = 11.40, 54.71% female) were assessed for GAD symptom severity (Composite International Diagnostic Interview-Short Form) across three waves, spaced about 9 years apart. Three aspects of EF [inhibition, set-shifting, and mixing costs (MCs; a measure related to common EF)], were assessed with stop-and-go switch tasks. Participants responded to 20 normal and 20 reverse single-task block trials and 32 mixed-task switch block trials. EF tests were administered at time 2 (T2) and time 3 (T3), but not at time 1 (T1). RESULTS: After controlling for T1 depression, LCS models revealed that within-person increased T1 - T2 GAD severity substantially predicted future reduced T2 - T3 inhibition and set-shifting (both indexed by accuracy and latency), and MC (indexed by latency) with moderate-to-large effect sizes (|d| = 0.51-0.96). CONCLUSIONS: Results largely support scar theories by offering preliminary within-person, naturalistic evidence that heightened excessive worry can negatively predict future distinct aspects of cognitive flexibility. Effectively targeting pathological worry might prevent difficulties arising from executive dysfunction.

Larger increase in trait negative affect is associated with greater future cognitive decline and vice versa across 23 years.

BACKGROUND: Trait negative affect (NA) is a central feature of anxiety and depression disorders. Neurocognitive and scar models propose that within-person increase in NA across one period of time relates to a decline in cognitive functioning at a future period of time and vice versa. Yet, there has been little research on whether a within-person change in trait NA across one time-lag precedes and is associated with a change in cognition across a future time lag and vice versa. Due to a growing aging population, such knowledge can inform evidence-based prevention. METHODS: Participants were 520 dementia-free community-dwelling adults (mean age = 59.76 years [standard deviation = 8.96], 58.08% females). Trait-level NA (negative emotionality scale), spatial cognition (block design and card rotations), verbal working memory (WM; digit span backward), and processing speed (symbol digit modalities) were assessed at five time points (waves) across 23 years. Bivariate dual latent change score (LCS) approaches were used to adjust for regression to the mean, lagged outcomes, and between-person variability. RESULTS: Unique bivariate LCS models showed that within-person increase in trait NA across two sequential waves was related to declines in spatial cognition, verbal WM, and processing speed across the subsequent two waves. Moreover, within-person reductions in spatial cognition, verbal WM, and processing speed across two sequential waves were associated with future increases in trait NA across the subsequent two waves. CONCLUSIONS: Findings concur with neurobiological and scar theories of psychopathology. Furthermore, results support process-based emotion regulation models that highlight the importance of verbal WM, spatial cognition, and processing speed capacities for downregulating NA.

Executive function and other cognitive deficits are distal risk factors of generalized anxiety disorder 9 years later.

OBJECTIVE: The cognitive model (Hirsch & Mathews, 2012) and attentional control theory (Eysenck & Derakshan, 2011) postulate that compromised executive function (EF) and other cognitive constructs are negatively linked to increased excessive and uncontrollable worry, the core symptom of generalized anxiety disorder (GAD). However, the prospective link between neuropsychological constructs and GAD are not well understood. METHODS: A nationally representative sample of 2605 community-dwelling adults whose average age was 55.20 (s.d. = 11.41, range 33-84; 56.31% females) participated at baseline and 9-year follow-up. Baseline neuropsychological function and symptoms were measured using the Brief Test of Adult Cognition by Telephone and Composite International Diagnostic Interview - Short Form. Multivariate Poisson and negative binomial regression analyses were conducted with 11 baseline covariates entered simultaneously: age, gender, years of formal education, perceived control, hypertension/diabetes, body mass index, exercise status, as well as GAD severity, panic disorder severity, and depression severity. Those with baseline GAD were also removed. RESULTS: Lower Time 1 composite global cognition z-score independently predicted higher Time 2 GAD severity and diagnosis [odds ratio (OR) 0.60, 95% confidence interval (CI) 0.40-0.89, p = 0.01]. Poor inhibition, set-shifting, working memory (WM) updating, inductive reasoning, and global cognition sequentially forecasted heightened GAD. However, processing speed, verbal WM, verbal fluency, and episodic memory did not predict future GAD. CONCLUSION: Global cognition, inductive reasoning, inhibition, set-shifting, and WM updating EF impairments may be distal risk factors for elevated GAD nearly a decade later.

Diffusion tensor imaging studies in late-life depression: systematic review and meta-analysis.

OBJECTIVES: Late-life depression (LLD) is the association with more cerebrovascular susceptibilities and white matter damage that can be assessed with diffusion tensor imaging (DTI). To better understand the white matter pathological alterations in LLD, we conducted a systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, PsycINFO, PubMed, and Google Scholar databases for DTI studies comparing patients with LLD and healthy controls. For each study, details regarding participants, imaging methods, and results were extracted. Fractional anisotropy, an index of white matter integrity, was the dependent variable for group comparison. Effect sizes indicating the degree of group difference were estimated by random-effects meta-analysis. RESULTS: A total of 15 eligible studies were included in the qualitative systematic review, nine of which were suitable for quantitative meta-analyses for the dorsolateral prefrontal cortex (DLPFC), corpus callosum, cingulum, and uncinate fasciculus (UF). Compared with the healthy control group, the LLD group showed lower fractional anisotropy in the DLPFC and UF with a large and a medium effect size, respectively, although heterogeneity and publication bias were found in the DLPFC. CONCLUSION: Diffusion tensor imaging studies of LLD consistently showed reduced anisotropy in the DLPFC and UF of patients with LLD. These damaged regions are located with the frontostriatal and limbic networks. Thus, our findings showed that the disruption of frontal and frontal-to-limbic white matter tracts contributes to the pathogenesis of LLD.

Examining the Effects of a Brief, Fully Self-Guided Mindfulness Ecological Momentary Intervention on Empathy and Theory-of-Mind for Generalized Anxiety Disorder: Randomized Controlled Trial.

BACKGROUND: The utility of brief mindfulness ecological momentary interventions (EMIs) to improve empathy and theory-of-mind has been underinvestigated, particularly in generalized anxiety disorder (GAD). OBJECTIVE: In this randomized controlled trial, we aimed to examine the efficacy of a 14-day, fully self-guided, mindfulness EMI on the empathy and theory-of-mind domains for GAD. METHODS: Adults (aged ≥18 y) diagnosed with GAD were randomized to a mindfulness EMI (68/110, 61.8%) or self-monitoring app (42/110, 38.2%) arm. They completed the Interpersonal Reactivity Index self-report empathy measure and theory-of-mind test (Bell-Lysaker Emotion Recognition Task) at prerandomization, postintervention, and 1-month follow-up (1MFU) time points. Hierarchical linear modeling was conducted with the intent-to-treat principle to determine prerandomization to postintervention (pre-post intervention) and prerandomization to 1MFU (pre-1MFU) changes, comparing the mindfulness EMI to self-monitoring. RESULTS: Observed effects were generally stronger from pre-1MFU than from pre-post intervention time points. From pre-post intervention time points, the mindfulness EMI was more efficacious than the self-monitoring app on fantasy (the ability to imagine being in others' shoes; between-intervention effect size: Cohen d=0.26, P=.007; within-intervention effect size: Cohen d=0.22, P=.02 for the mindfulness EMI and Cohen d=-0.16, P=.10 for the self-monitoring app). From pre-1MFU time points, the mindfulness EMI, but not the self-monitoring app, improved theory-of-mind (a window into others' thoughts and intentions through abstract, propositional knowledge about their mental states, encompassing the ability to decipher social cues) and the fantasy, personal distress (stress when witnessing others' negative experiences), and perspective-taking (understanding others' perspective) empathy domains. The effect sizes were small to moderate (Cohen d=0.15-0.36; P<.001 to P=.01) for significant between-intervention effects from pre-1MFU time points. Furthermore, the within-intervention effect sizes for these significant outcomes were stronger for the mindfulness EMI (Cohen d=0.30-0.43; P<.001 to P=.03) than the self-monitoring app (Cohen d=-0.12 to 0.21; P=.001 to P>.99) from pre-1MFU time points. No between-intervention and within-intervention effects on empathic concern (feeling affection, compassion, and care when observing others in distress, primarily attending to their emotional well-being) were observed from pre-post intervention and pre-1MFU time points. CONCLUSIONS: The brief mindfulness EMI improved specific domains of empathy (eg, fantasy, personal distress, and perspective-taking) and theory-of-mind with small to moderate effect sizes in persons with GAD. Higher-intensity, self-guided or coach-facilitated, multicomponent mindfulness EMIs targeting the optimization of social relationships are likely necessary to improve the empathic concern domain in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04846777; https://clinicaltrials.gov/study/NCT04846777.

Reliability (or lack thereof) of smartphone ecological momentary assessment of visual dot probe attention bias toward threat indices.

BACKGROUND AND OBJECTIVES: Cognitive bias theories posit that generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are entwined with attention bias toward threats, commonly indexed by faster response time (RT) on threat-congruent (vs. threat-incongruent) trials on the visual dot probe. Moreover, although smartphone ecological momentary assessment (EMA) of the visual dot probe has been developed, their psychometric properties are understudied. This study thus aimed to assess the reliability of 8 smartphone-delivered visual dot probe attention bias and related indices in persons with and without GAD and SAD. METHODS: Community-dwelling adults (n = 819; GAD: 64%; SAD: 49%; Mixed GAD and SAD: 37%; Non-GAD/SAD Controls: 24%) completed a five-trial smartphone-delivered visual dot probe for a median of 60 trials (12 sessions x 5 trials/session) and an average of 100 trials (20 sessions x 5 trials/session). RESULTS: As hypothesized, Global Attention Bias Index, Disengagement Effect, and Facilitation Bias had low-reliability estimates. However, retest-reliability and internal reliability were good for Trial-Level Bias Scores (TLBS) (Bias Toward Treat: intra-class correlation coefficients (ICCs) = 0.626-0.644; split-half r = 0.640-0.670; Attention Bias Variability: ICCs = 0.507-0.567; split-half r = 0.520-0.580) and (In)congruent RTs. Poor retest-reliability and internal reliability estimates were consistently observed for all traditional attention bias and related indices but not TLBS. LIMITATIONS: Our visual dot probe EMA should have administered ≥320 trials to match best-practice guidelines based on similar laboratory studies. CONCLUSIONS: Future research should strive to examine attention bias paradigms beyond the dot-probe task that evidenced meaningful test-retest reliability properties in laboratory and real-world naturalistic settings.

Treatment condition as a moderator and change in trait mindfulness as a mediator of a brief mindfulness ecological momentary intervention for generalized anxiety disorder.

BACKGROUND: Theories propose that judgment of and reactivity to inner experiences are mediators of the effect of mindfulness-based interventions on generalized anxiety disorder (GAD). However, no study has tested such theories using brief, mindfulness ecological momentary intervention (MEMI). We thus tested these theories using a 14-day MEMI versus self-monitoring app (SM) control for GAD. METHODS: Participants (N = 110) completed self-reports of trait mindfulness (Five Facet Mindfulness Questionnaire), GAD severity (GAD-Questionnaire-IV), and trait perseverative cognitions (Perseverative Cognitions Questionnaire) at prerandomization, posttreatment, and 1-month follow-up (1MFU). Counterfactual mediation analyses with temporal precedence were conducted. RESULTS: Improvement in pre-post mindfulness domains (acceptance of emotions, describing feelings accurately, acting with awareness, judgment of inner experience, and reactivity to inner experience) predicted pre-1MFU reduction in GAD severity and pre-1MFU reduction in trait perseverative cognitions from MEMI but not SM. MEMI reduced pre-post reactivity to inner experiences (but not other mindfulness domains) significantly more than SM. Only reduced pre-post reactivity significantly mediated stronger efficacy of MEMI over SM on pre-1MFU reductions in GAD severity (indirect effect: ß = -2.970 [-5.034, -0.904], p = .008; b path: ß = -3.313 [-6.350, -0.276], p = .033; percentage mediated: 30.5%) and trait perseverative cognitions (indirect effect: ß = -0.153 [-0.254, -0.044], p = .008; b path: ß = -0.145 [-0.260, -0.030], p = .014; percentage mediated: 42.7%). Other trait mindfulness domains were non-significant mediators. CONCLUSIONS: Reactivity to inner experience might be a mindfulness-based intervention change mechanism and should be targeted to optimize brief MEMIs for GAD.

Which client with generalized anxiety disorder benefits from a mindfulness ecological momentary intervention versus a self-monitoring app? Developing a multivariable machine learning predictive model.

Precision medicine methods (machine learning; ML) can identify which clients with generalized anxiety disorder (GAD) benefit from mindfulness ecological momentary intervention (MEMI) vs. self-monitoring app (SM). We used randomized controlled trial data of MEMI vs. SM for GAD (N = 110) and tested three ML models to predict one-month follow-up reliable improvement in GAD severity, perseverative cognitions (PC), trait mindfulness (TM), and executive function (EF). Eleven baseline predictors were tested regarding differential reliable change from MEMI vs. SM (age, sex, race, EF errors, inhibitory dyscontrol, set-shifting deficits, verbal fluency, working memory, GAD severity, TM, PC). The final top five prescriptive predictor models of all outcomes performed well (AUC = .752 .886). The following variables predicted better outcome from MEMI vs. SM: Higher GAD severity predicted more GAD improvement but less EF improvement. Elevated PC, inhibitory dyscontrol, and verbal dysfluency predicted better improvement in most outcomes. Greater set-shifting and TM predicted stronger improvements in GAD symptoms and TM. Older age predicted more alleviation of GAD and PC symptoms. Women exhibited more enhancements in trait mindfulness and EF than men. White individuals benefitted more than non-White. PC, TM, EF, and sociodemographic data might help predictive models optimize intervention selection for GAD.

Daily stress reactivity and risk appraisal mediates childhood parental abuse predicting adulthood psychopathology severity: An 18-year longitudinal mediation analysis.

Identifying mechanisms of childhood abuse-adulthood psychopathology relations could facilitate preventive efforts, but most prior studies used cross-sectional or two-wave designs and did not test the effects of childhood maternal and paternal abuse separately. Our 18-year three-wave study thus determined if Wave 2 daily stress reactivity and risk appraisal severity mediated Wave 1 retrospectively-reported childhood maternal and paternal abuse on Wave 3 generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD), alcohol (AUD), and substance use disorder (SUD) self-rated symptom severity. Longitudinal structural equation modeling was employed, adjusting for Wave 1 psychopathology severity. Higher childhood maternal and paternal abuse consistently predicted greater future daily stress reactivity and risk appraisal, and these mediators subsequently predicted increased GAD, MDD, and PD, but not AUD and SUD severity. Daily stress reactivity and risk appraisal consistently mediated the pathways between childhood maternal and paternal abuse predicting heightened adulthood GAD, MDD, and PD (Cohen's d = 0.333-0.888) but not AUD and SUD severity. Mediation effect sizes were stronger for childhood maternal (24.5-83.0%) than paternal (19.5-56.0%) abuse as the predictor. The latent interaction between Wave 1 childhood maternal and paternal abuse did not moderate the effect of Wave 1 maternal or paternal abuse on any Wave 3 adulthood psychopathology severity through Wave 2 daily stress reactivity and risk appraisal. Our research emphasizes the urgent requirement for continuous evaluation and intervention initiatives in trauma-informed care, both in inpatient and outpatient treatment settings.