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Abstract Background Paediatric Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is relatively common and disabling with a mean time out of school of more than one academic year. NICE guidelines recommend referral to specialist services immediately if severely affected, within 3 months if moderately affected and within 6 months if mildly affected. However, the median time-to-assessment by a specialist service in the UK is 18 months. This study used a mixed-methods approach to examine factors associated with time taken to access specialist services. Methods Time-to-assessment was analysed as a continuous "survival-time" variable in Cox regression models using data from self-completed assessment forms for children attending a regional specialist CFS/ME service between January 2006 and December 2009. Semi-structured interviews about barriers experienced in accessing healthcare for their child were conducted with nine parents of children aged < 17 years (8 individual and one parent couple). Interviews were digitally recorded and analysed using "thematic analysis". Results 405 children were assessed between 2006 and 2009 and information on school attendance was available on 388. Only 1/125 with severe CFS/ME and 49/263 (19%) with mild to moderate CFS/ME were seen within NICE recommended timeframe. Increased fatigue was associated with shorter time to assessment (HR = 1.15; 95% CI 1.03, 1.29 per unit increase in Chalder fatigue score; P = 0.01). Time-to-assessment was not associated with disability, mood, age or gender. Parents described difficulties accessing specialist services because of their own as well as their GP's and Paediatrician's lack of knowledge. They experienced negative attitudes and beliefs towards the child's condition when they consulted GPs, Paediatricians and Child Psychiatrists. Parents struggled to communicate an invisible illness that their child and not themselves were experiencing. Conclusions GPs, Child Psychiatrists and Paediatricians need more knowledge about CFS/ME and the appropriate referral pathways to ensure timeliness in referral to specialist services.

Abstract Background The morphological and functional differences between arteries and veins may have implications on coronary artery bypass graft (CABG) survival. Although subjective differences have been observed between radial artery (RA) and long saphenous venous (LSV) grafts, these have not been quantified. This study assessed and compared the flow characteristics and in-vivo graft flow responses of RA and LSV aorto-coronary grafts. Methods Angiograms from 52 males taken 3.7 ± 1.0 months after CABG surgery were analyzed using adjusted Thrombolysis in Myocardial Infarction (TIMI) frame count. Graft and target coronary artery dimensions were measured using quantitative coronary angiography. Estimated TIMI velocity (VE) and volume flow (FE) were then calculated. A further 7 patients underwent in-vivo graft flow responses assessments to adenosine, acetylcholine and isosorbide dinitrate (ISDN) using intravascular Doppler. Results The VE for RA grafts was significantly greater than LSV grafts (P = 0.002), however there was no difference in volume FE (P = 0.20). RA grafts showed positive endothelium-dependent and -independent vasodilatation, and LSV grafts showed no statistically significant response to adenosine and acetylcholine. There was no difference in flow velocity or volume responses. Seven RA grafts (11%) had compromised patency (4 (6%) ≥ 50% stenosis in the proximal/distal anastomoses, and 3 (5%) diffuse narrowing). Thirty-seven (95%) LSV grafts achieved perfect patency and 2 (5%) were occluded. Conclusion The flow characteristics and flow responses of the RA graft suggest that it is a more physiological conduit than the LSV graft. The clinical relevance of the balance between imperfect patency versus the more physiological vascular function in the RA graft may be revealed by the 5-year angiographic follow-up of this trial.

The purpose of this study was to examine how teachers help and hinder students who struggle academically. Thirty nurse educators from 18 different schools of nursing shared stories of how they helped and hindered their academically at-risk students. Hermeneutic analysis revealed several themes. This article addresses the pattern of attending and two themes: attending as understanding and attending as expecting. [ABSTRACT FROM AUTHOR]

Background: Depression is linked to cognitive biases towards more negative and less positive self-relevant information. Rumination, perseverative negative thinking about the past and the self, may contribute to these biases., Methods: 159 adolescents (12-18 years), with a range of depression symptoms, completed the SRET during fMRI. Multiple regressions tested associations between conventional self-report and ecological momentary assessment (EMA) measured rumination, and neural and behavioral responses during a self-referent encoding task (SRET)., Results: Higher rumination (conventional self-report and EMA) was associated with more negative and fewer positive words endorsed and recalled. Higher self-reported (but not EMA) rumination was associated with higher accuracy in recognizing negative words and greater insula and dorsal anterior cingulate activity to negative versus positive words., Limitations: The sample included mostly non-Hispanic White participants with household incomes above the national average, highlighting the need for replication in more diverse samples. Word endorsement discrepancies required fMRI analyses to model neural response to viewing negative versus positive words., Conclusions: Adolescents with higher rumination endorsed and recalled more negative and fewer positive words and recognized more negative words during the SRET. Higher insula reactivity, a key region for modulating externally-oriented attention and internally-oriented self-referential processes, may contribute to links between rumination and negative memory biases. These findings provide insight into neurocognitive mechanisms underlying depression., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cognitive behavioral therapy (CBT) is a gold-standard approach for treating major depressive disorder in adolescents. However, nearly half of adolescents receiving CBT do not improve. To personalize treatment, it is essential to identify objective markers that predict treatment responsiveness. To address this aim, we investigated neurophysiological processes related to self-referential processing that predicted CBT response among female adolescents with depression., Methods: At baseline, female adolescents ages 13 to 18 years (N = 80) completed a comprehensive clinical assessment, and a self-referential encoding task was administered while electroencephalographic data were recorded. Baseline electroencephalographic data were utilized to identify oscillatory differences between healthy adolescents (n = 42) and adolescents with depression (n = 38). Following the baseline assessment, adolescents with depression received up to 12 weeks of CBT. Baseline differences in electroencephalographic oscillations between healthy adolescents and those with depression were used to guide CBT prediction analysis. Cluster-based event-related spectral perturbation analysis was used to probe theta and alpha event-related synchronization (ERS)/event-related desynchronization (ERD) response to negative and positive words., Results: Baseline analyses showed that, relative to the healthy adolescents, adolescents with depression exhibited higher levels of frontal theta ERS and greater posterior alpha ERD. Multilevel modeling identified primary neural pretreatment predictors of treatment response: greater theta ERS in the right prefrontal cortex after the onset of negative words and lower alpha ERD in both the right prefrontal cortex and posterior cingulate cortex. ERS and ERD associations with treatment response remained significant, with baseline depressive and anxiety symptoms included as covariates in all analyses., Conclusions: Consistent with prior research, results highlighted that relative to healthy adolescents, adolescents with depression are characterized by prominent theta synchronization and alpha desynchronization over the prefrontal cortex and posterior cingulate cortex, respectively. Cluster-based event-related spectral perturbation analysis also identified key mechanisms underlying depression-related self-referential processing that predicted improved symptoms during the course of CBT. Ultimately, a better characterization of the neural underpinnings of adolescent depression and its treatment may lead to more personalized interventions., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Meditation practice and psychedelic use have attracted increasing attention in the public sphere and scientific research. Both methods induce non-ordinary states of consciousness that may have significant therapeutic benefits. Thus, there is growing scientific interest in potential synergies between psychedelic use and meditation practice with some research suggesting that psychedelics may benefit meditation practice. The present study examined individual, psychedelic-related, and meditation-related factors to determine under what conditions meditators perceive psychedelic use as beneficial for their meditation practice., Method: Participants ( N = 863) who had reported psychedelic use and a regular meditation practice (at least 3 times per week during the last 12 months) were included in the study. To accommodate a large number of variables, machine learning (i.e., elastic net, random forest) was used to analyze the data., Results: Most participants ( n = 634, 73.5%) found psychedelic use to have a positive influence on their quality of meditation. Twenty-eight variables showed significant zero-order associations with perceived benefits even following a correction. Elastic net had the best performance (R 2 = .266) and was used to identify the most important features. Across 53 variables, the model found that greater use of psychedelics, intention setting during psychedelic use, agreeableness, and exposure to N,N-Dimethyltryptamine (N,N-DMT) were most likely to be associated with the perception that psychedelics benefit meditation practice. The results were consistent across several different approaches used to identify the most important variables (i.e., Shapley values, feature ablation)., Discussion: Results suggest that most meditators found psychedelic use to have a positive influence on their meditation practice, with: 1) regularity of psychedelic use, 2) the setting of intentions for psychedelic use, 3) having an agreeable personality, and 4) reported use of N,N-DMT being the most likely predictors of perceiving psychedelic use as beneficial. Longitudinal designs and randomized trials manipulating psychedelic use are needed to establish causality.

Objective: Behavioral activation (BA) is a brief intervention for depression encouraging gradual and systematic re-engagement with rewarding activities and behaviors. Given this treatment focus, BA may be particularly beneficial for adolescents with prominent anhedonia, a predictor of poor treatment response and common residual symptom. We applied group iterative multiple model estimation (GIMME) to ecological momentary assessment (EMA) treatment data to investigate common and person-specific processes during BA for anhedonic adolescents., Method: Thirty-nine adolescents ( M age = 15.7 years old, 67% female, 81% White) with elevated anhedonia (Snaith-Hamilton Pleasure Scale) were enrolled in a 12-week BA trial, with weekly anhedonia assessments. EMA surveys were triggered every other week (2-3 surveys per day) throughout treatment assessing current positive affect (PA) and negative affect (NA), engagement in pleasurable activities and social interactions, anticipatory pleasure, rumination, and recent pleasurable and stressful experiences., Results: A multilevel model revealed significant decreases in anhedonia, t (25.5) = -4.76, p < .001, over the 12-week trial. GIMME results indicated substantial heterogeneity in variable networks across patients. PA was the variable with the greatest number (22% of all paths vs. 11% for NA) of predictive paths to other symptoms (i.e., highest out-degree). Higher PA (but not NA) out-degree was associated with greater anhedonia improvement, t (25.8) = -2.22, p = .035., Conclusions: Results revealed substantial heterogeneity in variable relations across patients, which may obscure the search for common processes of change in BA. PA may be a particularly important treatment target for anhedonic adolescents in BA. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Poor inhibitory control contributes to deficits in emotion regulation, which are often targeted by treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT). Brain regions that contribute to inhibitory control and emotion regulation overlap; thus, inhibitory control might relate to response to CBT. In this study, we examined whether baseline inhibitory control and resting state functional connectivity (rsFC) within overlapping emotion regulation-inhibitory control regions predicted treatment response to internet-based CBT (iCBT). Participants with MDD were randomly assigned to iCBT (N = 30) or a monitored attention control (MAC) condition (N = 30). Elastic net regression was used to predict post-treatment Patient Health Questionnaire-9 (PHQ-9) scores from baseline variables, including demographic variables, PHQ-9 scores, Flanker effects (interference, sequential dependency, post-error slowing), and rsFC between the dorsal anterior cingulate cortex, bilateral anterior insula (AI), and right temporoparietal junction (TPJ). Essential prognostic predictor variables retained in the elastic net regression included treatment group, gender, Flanker interference response time (RT), right AI-TPJ rsFC, and left AI-right AI rsFC. Prescriptive predictor variables retained included interactions between treatment group and baseline PHQ-9 scores, age, gender, Flanker RT, sequential dependency effects on accuracy, post-error accuracy, right AI-TPJ rsFC, and left AI-right AI rsFC. Inhibitory control and rsFC within inhibitory control-emotion regulation regions predicted reduced symptom severity following iCBT, and these effects were stronger in the iCBT group than in the MAC group. These findings contribute to a growing literature indicating that stronger inhibitory control at baseline predicts better outcomes to psychotherapy, including iCBT., (© 2024. The Author(s).)

Objective: A recent randomized controlled trial (RCT) indicated that individuals with higher levels of attachment anxiety exhibited better treatment outcomes in supportive-expressive therapy (SET) relative to supportive therapy (ST). But to gain insight into within-patient therapeutic changes, a within-individual design is required. The present study contrasts previous findings based on theory-driven between-patient moderators with data-driven moderators of within-patient processes to investigate whether findings converge or diverge across these two approaches., Method: We used data of 118 patients from the pilot and active phases of a recent RCT for patients with major depressive disorder, comparing ST with SET, a time-limited psychodynamic therapy. The predefined primary outcome measure was the Hamilton Rating Scale for Depression. Supportive versus expressive techniques were rated based on patients' end-of-session perspective. We compared previous findings based on moderators of between-patient effects with a data-driven approach for identifying moderators of within-patient effects of techniques on subsequent outcome., Results: After false discovery rate corrections, of 10 preselected moderators, patients' attachment anxiety and domineering style remained significant. Of these, bootstrap resampling revealed significant differences between ST and SET techniques for the attachment anxiety moderator: Those with higher attachment anxiety benefited more from greater use of ST than SET techniques in a particular session, as evidenced by lower levels of symptoms at the subsequent session., Conclusions: Our within-individual findings diverge from previously published between-individual analyses. This proof-of-concept study demonstrates the importance of complementing between-individuals with within-individual analyses to achieve better understanding of who benefits most from specific treatment techniques. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Obsessive-compulsive and related disorders (OCRDs) are associated with increased risk of suicidal thoughts and behaviors (STBs), yet research characterizing suicidality in OCRDs remains limited. A major challenge in assessing STBs is the reliance on explicit self-report. This study utilized multi-method assessment to examine changes in both implicit and explicit STBs in 31 adults receiving partial/residential treatment for OCRDs. Assessments were administered at admission and weekly during treatment. Approximately three-quarters of participants reported lifetime suicidal thoughts, with 16 % reporting a prior suicide attempt. OCD severity was significantly correlated with lifetime suicidal thoughts, and was significantly higher for those with lifetime suicidal thoughts and prior attempts compared to those without. Implicit biases towards death were not associated with OCD severity, and did not predict explicitly endorsed STBs. This is the first study to measure both explicit and implicit STBs in adults with OCRDs. Limitations included small sample size and lack of racial/ethnic diversity. Given the majority had recent suicidal thoughts and one in six had a prior attempt, we emphasize the importance of STB assessment in OCD treatment settings., Competing Interests: Declaration of competing interest For the manuscript, “Multi-method assessment of suicidal thoughts and behaviors among patients in treatment for OCD and related disorders” re-submitted on 1/11/2024, there are no interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Effective psychosocial interventions exist for numerous mental health conditions. However, despite decades of research, limited progress has been made in clarifying the mechanisms that account for their beneficial effects. We know that many treatments work, but we know relatively little about why they work. Mechanisms of change may be obscured due to prior research collapsing across heterogeneous subgroups of patients with differing underlying mechanisms of response. Studies identifying baseline individual characteristics that predict differential response (i.e., moderation) may inform research on why (i.e., mediation) a particular subgroup has better outcomes to an intervention via tests of moderated mediation., Method: In a recent randomized controlled trial comparing a 4-week meditation app with a control condition in school system employees ( N = 662), we previously developed a "Personalized Advantage Index" (PAI) using baseline characteristics, which identified a subgroup of individuals who derived relatively greater benefit from meditation training. Here, we tested whether the effect of mindfulness acquisition in mediating group differences in outcome was moderated by PAI scores., Results: A significant index of moderated mediation (IMM = 1.22, 95% CI [0.30, 2.33]) revealed that the effect of mindfulness acquisition in mediating group differences in outcome was only significant among those individuals with PAI scores predicting relatively greater benefit from the meditation app., Conclusions: Subgroups of individuals may differ meaningfully in the mechanisms that mediate their response to an intervention. Considering subgroup-specific mediators may accelerate progress on clarifying mechanisms of change underlying psychosocial interventions and may help inform which specific interventions are most beneficial for whom. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Competing Interests: Declaration of competing interest Michael Barkham has co-produced outcome measures used in routine outcome monitoring and also jointly published a text on routine outcome monitoring but receives no financial payment for these activities. Christopher G. Beevers has received funding for his research from the National Institutes of Health, Brain and Behavior Foundation, Aiberry Inc., and other private, not-for-profit foundations. He has received income from the Association for Psychological Science for his editorial work and from Orexo, Inc. for serving on a Scientific Advisory Board related to digital therapeutics. Dr. Beevers' financial disclosures have been reviewed and approved by the University of Texas at Austin in accordance with its conflict-of-interest policies. Tim Dalgleish has received payment for consultancy work with Princeton Biopartners, Boehringer Ingelheim and Felix Inc. He delivers paid workshops on psychological therapies. He receives royalties for books on affect and psychological disorders. Nicholas C. Jacobson declares the following conflicts of interest. He has edited a book that includes discussion of this topic from which he receives royalties. Additionally, he has accepted paid speaking invitations from various organizations. Dr. Jacobson confirms that these interests do not influence the research, interpretation, or conclusions presented in this manuscript. Daniel R. Karlin is an employee, officer, and shareholder of MindMed; shareholder and director at Sonara Health; trustee at Trudeau Institute; shareholder and consultant to NightWare; consultant to Otsuka, Tempus, Limitless Ventures, Recovery Delivered, and 4YouandMe. Cheri A. Levinson has a financial interest in BeWell and Awaken Digital Solutions. Lorenzo Lorenzo-Luaces has received consulting fees from Syra Health who had no involvement in the current research. Stephen M. Schueller serves on the Scientific Advisory Board for Headspace for which he receives compensation and has received consulting payments from Boehringer Ingelheim, K Health (Trusst), and Otsuka Pharmaceuticals for unrelated work. Greg J. Siegle receives royalty payments on a patent regarding a vibroacoustic intervention for psychiatric conditions, licensed to Apollo Neurosciences. Wolfgang Lutz and Eva-Lotta Brakemeier initiated and chair the Interest Group "Evidence-Based Personalized Psychotherapy Research (ePePsy)" of the German Psychological Association.

Background: Adolescence is characterized by profound change, including increases in negative emotions. Approximately 84% of American adolescents own a smartphone, which can continuously and unobtrusively track variables potentially predictive of heightened negative emotions (e.g. activity levels, location, pattern of phone usage). The extent to which built-in smartphone sensors can reliably predict states of elevated negative affect in adolescents is an open question., Methods: Adolescent participants ( n = 22; ages 13-18) with low to high levels of depressive symptoms were followed for 15 weeks using a combination of ecological momentary assessments (EMAs) and continuously collected passive smartphone sensor data. EMAs probed negative emotional states (i.e. anger, sadness and anxiety) 2-3 times per day every other week throughout the study (total: 1145 EMA measurements). Smartphone accelerometer, location and device state data were collected to derive 14 discrete estimates of behavior, including activity level, percentage of time spent at home, sleep onset and duration, and phone usage., Results: A personalized ensemble machine learning model derived from smartphone sensor data outperformed other statistical approaches (e.g. linear mixed model) and predicted states of elevated anger and anxiety with acceptable discrimination ability (area under the curve (AUC) = 74% and 71%, respectively), but demonstrated more modest discrimination ability for predicting states of high sadness (AUC = 66%)., Conclusions: To the extent that smartphone data could provide reasonably accurate real-time predictions of states of high negative affect in teens, brief 'just-in-time' interventions could be immediately deployed via smartphone notifications or mental health apps to alleviate these states.

Fear extinction is the basis of exposure therapies for posttraumatic stress disorder (PTSD), but half of patients do not improve. Predicting fear extinction in individuals with PTSD may inform personalized exposure therapy development. The participants were 125 trauma-exposed adults (96 female) with a range of PTSD symptoms. Electromyography, electrocardiogram, and skin conductance were recorded at baseline, during dark-enhanced startle, and during fear conditioning and extinction. Using a cross-validated, hold-out sample prediction approach, three penalized regressions and conventional ordinary least squares were trained to predict fear-potentiated startle during extinction using 50 predictor variables (5 clinical, 24 self-reported, and 21 physiological). The predictors, selected by penalized regression algorithms, were included in multivariable regression analyses, while univariate regressions assessed individual predictors. All the penalized regressions outperformed OLS in prediction accuracy and generalizability, as indexed by the lower mean squared error in the training and holdout subsamples. During early extinction, the consistent predictors across all the modeling approaches included dark-enhanced startle, the depersonalization and derealization subscale of the dissociative experiences scale, and the PTSD hyperarousal symptom score. These findings offer novel insights into the modeling approaches and patient characteristics that may reliably predict fear extinction in PTSD. Penalized regression shows promise for identifying symptom-related variables to enhance the predictive modeling accuracy in clinical research.

The probabilistic reward task (PRT) has identified reward learning impairments in those with major depressive disorder (MDD), as well as anhedonia-specific reward learning impairments. However, attempts to validate the anhedonia-specific impairments have produced inconsistent findings. Thus, we seek to determine whether the Reward Behavior Disengagement (RBD), our proposed economic augmentation of PRT, differs between MDD participants and controls, and whether there is a level at which RBD is high enough for depressed participants to be considered objectively disengaged. Data were gathered as part of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a double-blind, placebo-controlled clinical trial of antidepressant response. Participants included 195 individuals with moderate to severe MDD (Quick Inventory of Depressive Symptomatology (QIDS-SR) score ≥ 15), not in treatment for depression, and with complete PRT data. Healthy controls ( n = 40) had no history of psychiatric illness, a QIDS-SR score < 8, and complete PRT data. Participants with MDD were treated with sertraline or placebo for 8 weeks (stage I of the EMBARC trial). RBD was applied to PRT data using discriminant analysis, and classified MDD participants as reward task engaged ( n = 137) or reward task disengaged ( n = 58), relative to controls. Reward task engaged/disengaged groups were compared on sociodemographic features, reward-behavior, and sertraline/placebo response (Hamilton Depression Rating Scale scores). Reward task disengaged MDD participants responded only to sertraline, whereas those who were reward task engaged responded to sertraline and placebo ( F (1293) = 4.33, p = 0.038). Reward task engaged/disengaged groups did not differ otherwise. RBD was predictive of reward impairment in depressed patients and may have clinical utility in identifying patients who will benefit from antidepressants.

Background: Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear., Methods: We recruited a sample of adolescents ( n = 82; ages 12-18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life., Results: Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome., Conclusions: Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.

Background: Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined., Methods: Fifty-two MDD patients were randomly assigned to either 10-week iCBT ( n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants ( n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart., Results: Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment., Conclusions: These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.

Anhedonia is a cardinal characteristic of depression which predicts worse treatment outcome and is among the most common residual symptoms following treatment. Behavioral Activation (BA) has been shown to be an effective treatment for depressed adults, and more recently, depressed adolescents. Given its emphasis on systematically and gradually increasing exposure to and engagement with rewarding activities and experiences, BA may be a particularly effective intervention for adolescents experiencing anhedonia and associated reward system dysfunction. In the present study, anhedonic adolescents (AA; n = 39) received 12 weekly sessions of BA and completed a multimodal (i.e., neural, behavioral, and self-report [ecological momentary assessment]) assessment of reward function at pre-treatment and post-treatment (as well as weekly self-report assessments of anhedonia). Typically developing adolescents (TDA; n = 41) completed the same measures at corresponding timepoints. Multilevel models tested pre-treatment reward-related predictors of anhedonia improvement, as well as change in reward measures over the course of BA. Analyses revealed significant reductions in anhedonia following BA treatment. Enhanced pre-treatment neural (striatal) reward responsiveness predicted greater anhedonia improvement. In contrast, baseline self-report and behavioral reward measures did not predict treatment outcome. A group x time interaction revealed greater increases in both reward- and loss-related neural responsiveness among AA relative to TDA adolescents. Consistent with a capitalization (rather than compensatory) model, pre-treatment neural - but not self-report or behavioral - measures of relatively enhanced reward responsiveness predicted better BA outcome. In addition to alleviating anhedonia, successful BA may also increase neural sensitivity to affectively salient (e.g., reward- and loss-related) stimuli among anhedonic youth., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Classic theories of stress and health are largely based on assumptions regarding how different psychosocial stressors influence biological processes that, in turn, affect human health and behavior. Although theoretically rich, this work has yielded little consensus and led to numerous conceptual, measurement, and reproducibility issues. Social Safety Theory aims to address these issues by using the primary goal and regulatory logic of the human brain and immune system as the basis for specifying the social-environmental situations to which these systems should respond most strongly to maximize reproductive success and survival. This analysis gave rise to the integrated, multi-level formulation described herein, which transforms thinking about stress biology and provides a biologically based, evolutionary account for how and why experiences of social safety and social threat are strongly related to health, well-being, aging, and longevity. In doing so, the theory advances a testable framework for investigating the biopsychosocial roots of health disparities as well as how health-relevant biopsychosocial processes crystalize over time and how perceptions of the social environment interact with childhood microbial environment, birth cohort, culture, air pollution, genetics, sleep, diet, personality, and self-harm to affect health. The theory also highlights several interventions for reducing social threat and promoting resilience.

Introduction: Patient populations differ for elective vs urgent and emergent surgery. The effect of this difference on surgical outcome is not well understood and may be important for improving surgical safety. Our primary hypothesis was that there is an association of surgical acuity with risk of postoperative cardiac events. Secondarily, we examined elective vs urgent and emergent patients separately to understand patient characteristics that are associated with postoperative cardiac events., Methods: We performed a retrospective cohort study of patients ≥65 years undergoing noncardiac elective or urgent/emergent surgery. Logistic regression estimated the association of surgical acuity with a postoperative cardiac event, which was defined as myocardial infarction or cardiac arrest within 30 days of surgery. For the secondary analysis, we modeled the outcome after stratifying by acuity., Results: The study included 161,177 patients with 1014 cardiac events. The unadjusted risk of a postoperative cardiac event was 3.2 per 1000 among elective patients and 28.7 per 1000 among urgent and emergent patients (adjusted odds ratio 4.10, 95% confidence interval 3.56-4.72). After adjustment, increased age, higher baseline cardiac risk, peripheral vascular disease, hypertension, worse American Society of Anesthesiologist (ASA) physical classification, and longer operative time were associated with a postoperative cardiac event. Higher baseline cardiac risk was more strongly associated with postoperative cardiac events in elective patients. In contrast, worse ASA physical classification was more strongly associated with postoperative cardiac events in urgent and emergent patients. Black patients had higher odds of a postoperative cardiac event only in urgent and emergent patients compared to White patients., Conclusions: Quality measurement and improvement to address postoperative cardiac risk should consider patients based on surgical acuity., Competing Interests: Declaration of Competing Interest The authors are employees of the Permanente Medical Group and have no other disclosures to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Rumination is a risk factor for the development of internalizing psychopathology that often emerges during adolescence. The goal of the present study was to test a mindfulness mobile app intervention designed to reduce rumination., Method: Ruminative adolescents ( N  = 152; 59% girls, 18% racial/ethnic minority, M age = 13.72, SD  = .89) were randomly assigned to use a mobile app 3 times per day for 3 weeks that delivered brief mindfulness exercises or a mood monitoring-only control. Participants reported on rumination, depressive symptoms and anxiety symptoms at baseline, post-intervention and at 3 follow-up timepoints: 6 weeks, 12 weeks, and 6 months post-intervention. Parents reported on internalizing symptoms., Results: There was a significant Time X Condition effect at post-intervention for rumination, depressive symptoms, and anxiety symptoms, such that participants in the mindfulness intervention showed improvements relative to those in the control condition. The effect for rumination lasted through the 6-week follow-up period; however, group differences were generally not observed throughout the follow-up period, which may indicate that continued practice is needed for gains to be maintained., Conclusions: This intervention may have the potential to prevent the development of psychopathology and should be tested in a longitudinal study assessing affective disorder onset, especially in populations with limited access to conventional, in person mental health care.This study was registered with Clinicaltrials.gov (Identifier NCT03900416).

Background: Mind-wandering has been linked to negative affect and depressive symptoms in adolescents. However, mind-wandering is an extremely broad and heterogenous cognitive construct. Some features of spontaneous thought may be related to increased negative affect, whereas others may improve affect, or have no emotional influence. We used ecological momentary assessment (EMA) to investigate the characteristics of spontaneous thoughts in adolescents and their differential relations with moment-to-moment affect., Method: One-hundred and sixteen adolescents (ages 13-18; Typical Mood (TM) = 58; Low Mood (LM) = 58) completed 5 days (2-3 times/day) of EMA (total 1,037 surveys) assessing current positive and negative affect (PA and NA) and dimensions of spontaneous thought. Multilevel models tested the relation between thought characteristics and affect., Results: Relative to the TM group, LM adolescents had a higher frequency of mind-wandering (38% vs. 56%) and negatively-valanced thoughts during episodes of mind-wandering (21% vs. 37%). Negatively-valenced, self-referential and past-oriented thoughts were each associated with higher NA, even when controlling for plausible confounds (e.g., engagement in an unpleasant activity or social interaction, depressive symptom severity). In contrast, task-focused and positively-valenced thoughts were uniquely linked to higher PA., Conclusion: Characteristics of spontaneous thought - including temporal orientation, self-referential quality, and task-relatedness - were differentially related to NA vs. PA in adolescents. If replicated, these findings could inform more nuanced assessments of and targeted interventions for specific dimensions of mind-wandering contributing to high NA vs. blunted PA in teens.

Background: Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line treatment but fails to control SE in about one-third of patients. Levetiracetam may be used for SE that is refractory to benzodiazepine therapy., Objective: To examine, by means of a systematic review, the role of IV levetiracetam for the treatment of SE in adults., Data Sources: MEDLINE, Embase, CENTRAL, and CINAHL databases were searched, from inception to August 18, 2020., Study Selection and Data Extraction: Included in this review were prospective randomized controlled trials comparing levetiracetam with another antiepileptic drug, given with or after a benzodiazepine, in adult patients with SE. The primary outcome was cessation of SE. Quality of evidence was assessed with the Cochrane risk-of-bias tool. Characteristics of the included studies were reported using descriptive statistics., Data Synthesis: Five studies compared IV levetiracetam with valproic acid, phenytoin (or its prodrug fosphenytoin), or both. All 5 studies found no statistically significant differences in efficacy or safety end points. There were numerically more cases of hypotension and respiratory failure with phenytoin, and more cases of psychiatric adverse effects (e.g., post-ictal psychosis) with levetiracetam., Conclusions: Available evidence suggests that levetiracetam is as effective as valproic acid or phenytoin for the cessation of SE in adults. Other factors should therefore dictate the choice of antiepileptic drug for patients with SE, such as adverse effect profile, logistics of administration, drug cost, inclusion on hospital formularies, and drug availability., Competing Interests: Competing interests: None declared., (2022 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Background: Meditation apps have surged in popularity in recent years, with an increasing number of individuals turning to these apps to cope with stress, including during the COVID-19 pandemic. Meditation apps are the most commonly used mental health apps for depression and anxiety. However, little is known about who is well suited to these apps., Objective: This study aimed to develop and test a data-driven algorithm to predict which individuals are most likely to benefit from app-based meditation training., Methods: Using randomized controlled trial data comparing a 4-week meditation app (Healthy Minds Program [HMP]) with an assessment-only control condition in school system employees (n=662), we developed an algorithm to predict who is most likely to benefit from HMP. Baseline clinical and demographic characteristics were submitted to a machine learning model to develop a "Personalized Advantage Index" (PAI) reflecting an individual's expected reduction in distress (primary outcome) from HMP versus control., Results: A significant group × PAI interaction emerged (t 658 =3.30; P=.001), indicating that PAI scores moderated group differences in outcomes. A regression model that included repetitive negative thinking as the sole baseline predictor performed comparably well. Finally, we demonstrate the translation of a predictive model into personalized recommendations of expected benefit., Conclusions: Overall, the results revealed the potential of a data-driven algorithm to inform which individuals are most likely to benefit from a meditation app. Such an algorithm could be used to objectively communicate expected benefits to individuals, allowing them to make more informed decisions about whether a meditation app is appropriate for them., Trial Registration: ClinicalTrials.gov NCT04426318; https://clinicaltrials.gov/ct2/show/NCT04426318., (©Christian A Webb, Matthew J Hirshberg, Richard J Davidson, Simon B Goldberg. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.11.2022.)

Background: Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner., Methods: In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16., Results: Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline., Conclusion: These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

Objective: Rumination heightens risk for depression and anxiety, which increase substantially during adolescence. Smartphone apps offer a convenient and cost-effective means for adolescents to access mindfulness training, which may reduce rumination. Despite their increasing popularity, it is unclear which adolescents benefit from mindfulness apps., Method: Adolescents (n = 152) with elevated trait rumination were randomly assigned to 3 weeks of app-based mindfulness training or a mood-monitoring control. Multilevel models tested group differences in state rumination change, assessed via ecological momentary assessment. Baseline adolescent characteristics were submitted to elastic net regularization models to develop a "Personalized Advantage Index" indicating an individual's expected outcome from the mindfulness app relative to the mood-monitoring control. Finally, we translated a predictive model (developed in an external sample) for personalized recommendations of expected benefit from the mindfulness app., Results: Adolescents in the mindfulness app condition reported significantly greater reductions in rumination than adolescents in the control condition. Individuals predicted to have better outcomes from the mindfulness app relative to mood monitoring had significantly greater reductions in rumination if randomly assigned to the mindfulness condition. In contrast, between-condition differences in outcome were not significant for adolescents predicted to have better outcomes in the mood-monitoring condition., Conclusions: Findings support the efficacy of a mindfulness app to reduce state rumination in adolescents, particularly among adolescents high in trait rumination. A predictive model is put forth, which could be used to objectively communicate expected mindfulness app outcomes to adolescents prior to engagement in app-based mindfulness training. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: The brain circuitry of depression and anxiety/fear is well-established, involving regions such as the limbic system and prefrontal cortex. We expand prior literature by examining the extent to which four discrete factors of anxiety (immediate state anxiety, physiological/panic, neuroticism/worry, and agitation/restlessness) among depressed outpatients are associated with differential responses during reactivity to and regulation of emotional conflict., Methods: A total of 172 subjects diagnosed with major depressive disorder underwent functional magnetic resonance imaging while performing an Emotional Stroop Task. Two main contrasts were examined using whole brain voxel wise analyses: emotional reactivity and emotion regulation. We also evaluated the association of these contrasts with the four aforementioned anxiety factors., Results: During emotional reactivity, participants with higher immediate state anxiety showed potentiated activation in the rolandic operculum and insula, while individuals with higher levels of physiological/panic demonstrated decreased activation in the posterior cingulate. No significant results emerged for any of the four factors on emotion regulation. When re-analyzing these statistically-significant brain regions through analyses of a subsample with (n = 92) and without (n = 80) a current anxiety disorder, no significant associations occurred among those without an anxiety disorder. Among those with an anxiety disorder, results were similar to the full sample, except the posterior cingulate was associated with the neuroticism/worry factor., Conclusions: Divergent patterns of task-related brain activation across four discrete anxiety factors could be used to inform treatment decisions and target specific aspects of anxiety that involve intrinsic processing to attenuate overactive responses to emotional stimuli., (Copyright © 2022. Published by Elsevier Ltd.)

Cognitive models implicate interpretation bias in the development and maintenance of obsessive compulsive and related disorders (OCRDs), and research supports Cognitive Bias Modification for Interpretation (CBM-I) in targeting this mechanism. However, prior studies in OCRDs have been limited to nonclinical populations, adolescents, and adults in a laboratory setting. This study evaluated the feasibility and acceptability of CBM-I as an adjunctive intervention during intensive/residential treatment (IRT) for adults with OCRDs. We modified a lab-based CBM-I training for adults seeking IRT for OCRDs, and conducted a feasibility trial (N = 4) and subsequent pilot RCT; participants (N = 31) were randomized to receive CBM-I or psychoeducation. Benchmarks were met for feasibility, acceptability, and target engagement. From pre- to post-intervention, the CBM-I group showed a large effect for change in interpretation bias (d = .90), whereas this effect was trivial (d = .06) for psychoeducation. This was the first study to evaluate CBM-I in naturalistic treatment for adults seeking IRT for OCRDs. Findings support the feasibility and acceptability of CBM-I in this novel sample and setting. A larger scale RCT is needed to determine whether CBM-I can enhance OCRD treatment response., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Rather than relying on a single psychotherapeutic orientation, most clinicians draw from a range of therapeutic approaches to treat their clients. To date, no data-driven approach exists for personalized predictions of which skill domain would be most therapeutically beneficial for a given patient. The present study combined ecological momentary assessment (EMA) and machine learning to test a data-driven approach for predicting patient-specific skill-outcome associations., Method: Fifty ( M age = 37 years old, 54% female, 84% White) adults received training in behavioral therapy (BT) and dialectical behavior therapy (DBT) skills within a behavioral health partial hospital program (PHP). Following discharge, patients received four EMA surveys per day for 2 weeks (total observations = 2,036) assessing the use of therapeutic skills and positive/negative affect (PA/NA). Clinical and demographic characteristics were submitted to elastic net regularization to predict, via cross-validation, patient-specific associations between the use of BT versus DBT skills and level of PA/NA., Results: Cross-validated accuracy was 81% (sensitivity = 93% and specificity = 63%) in predicting whether a patient would exhibit a stronger association between the use of BT versus DBT skills and PA level. Predictors of positive DBT skills-PA associations included higher levels of nonsuicidal self-injury (NSSI) and sleep disturbance, whereas predictors of positive BT skills-PA relations included higher emotional lability and anxiety disorder comorbidity, and lower psychomotor retardation/agitation and worthlessness/guilt. Corresponding models with NA yielded no predictors., Conclusions: Findings from this initial proof-of-concept study highlight the potential of data-driven approaches to inform personalized prescriptions of which skill domains may be most therapeutically beneficial for a given patient. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objectives: Rumination is a transdiagnostic risk factor for depression and anxiety, which surge during the adolescent years. Mindfulness training - with its emphasis on metacognitive awareness and present-moment attention - may be effective at reducing rumination. Mindfulness apps offer a convenient, engaging, and cost-effective means for accessing mindfulness training for teens. Despite their increasing popularity among adolescents, no study to date has investigated which teens are well-suited to app-based mindfulness training., Methods: Eighty adolescents ( M age = 14.01 years, 45% girls) with elevated rumination were enrolled in a 3-week trial of app-based mindfulness training. Repeated daily ecological momentary assessment (EMA) surveys assessed problem-focused and emotion-focused rumination immediately prior to and following each mindfulness exercise. Elastic net regularization (ENR) models tested baseline predictors of "immediate" (post-mindfulness exercise) and "cumulative" (post-3-week intervention) benefit from app-based mindfulness training., Results: Ninety percent (72/80) of adolescents completed the 3-week trial, and the mean number of mindfulness exercises completed was 28.7. Baseline adolescent characteristics accounted for 14%-25% of the variance in outcomes (i.e., reduction in problem-focused or emotion-focused rumination). Higher baseline rumination, and lower emotional suppression, predicted better immediate and cumulative outcomes. In contrast, female gender and older age predicted better immediate, but not cumulative, outcomes. Differences in results across outcome timeframes (immediate vs. cumulative) are discussed., Conclusions: Findings from this study highlight the potential of data-driven approaches to inform which adolescent characteristics may predict benefit from engaging with an app-based mindfulness training program. Additional research is needed to test these predictive models against a comparison (non-mindfulness) condition., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Sociotropy and autonomy are cognitive-personality styles that have been hypothesized to confer vulnerability to different presentations of major depressive disorder (MDD), which may respond differentially to treatment. Specifically, the profile of low sociotropy and high autonomy is hypothesized to indicate a positive response to antidepressant medication. The current study examines sociotropy and autonomy in relation to sertraline treatment response in individuals with MDD. As part of an ancillary study to the larger Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) project, individuals with MDD participated in an 8-week trial of sertraline and completed a self-report questionnaire of sociotropy and autonomy. Discriminant function analyses were used to examine whether sociotropy and autonomy scores could distinguish antidepressant treatment responders (determined by a 50% or greater reduction in depressive symptoms) from non-responders. The sociotropy scale successfully discriminated sertraline treatment responders from non-responders. Further, lower sociotropy was associated with greater improvements in depressive symptomology following sertraline treatment. The current findings suggest individuals with MDD characterized by low sociotropy are more likely to benefit from sertraline. Given the promising results of the Sociotropy-Autonomy Scale in discriminating treatment responders from non-responders, the low resources necessary for administration, and the ease of translation into routine clinical care, the scale warrants further research attention., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: Understanding the fluctuating emotional and cognitive states of adolescents with depressive symptoms requires fine-grained and naturalistic measurements. This study used ecological momentary assessment (EMA) to investigate the affective correlates and consequences of mind-wandering in adolescents with anhedonia (AH) and typically developing (TD) controls. In addition, we examined the association between mind-wandering and resting state functional connectivity between the medial prefrontal cortex (mPFC), a core hub of the default mode network (DMN) linked to internally oriented mentation, and networks linked to attentional control (dorsal attention network [DAN]) and affect/salience detection (salience network [SN])., Method: A total of 65 adolescents, aged 12 to 18 years (TD = 36; AH = 29), completed a resting state functional magnetic resonance imaging scan and subsequently used a smartphone application for ecological momentary assessment (EMA) data collection (2-3 times/d for 5 days). Each survey (N = 678) prompted adolescents to report on their current positive and negative affect (PA and NA), cognition, and activity., Results: The frequency of mind-wandering was higher for AH (70.0% of EMA samples) relative to TD (59.2%) participants, and the participants with AH were more likely to mind-wander to unpleasant content. Mind-wandering was associated with higher concurrent NA, even when controlling for plausible confounds (eg, current activity, social companion, rumination). Time-lagged analyses revealed a bidirectional association between mind-wandering and PA. Greater levels of mind-wandering within the AH group were associated with stronger mPFC-SN/DAN connectivity., Conclusion: Rates of mind-wandering were high, especially among adolescents with anhedonia, and predicted worse affect. The relation between mind-wandering and enhanced mPFC-SN coupling may reflect heightened bottom-up influence of affective and sensory salience on DMN-mediated internally oriented thought., (Copyright © 2020 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Hofmann et al. argued that "[w]hile the clinical field has produced a dizzying number of treatment models and treatment protocols for virtually every psychiatric and psychological problem imaginable, increases in understanding of the processes of change in psychotherapy has been slow to arrive." We propose that one of the reasons for the slow progress is that prior psychotherapy research conflates trait-like and state-like components of mechanisms of change. Trait-like components can serve as prescriptive or prognostic variables, whereas state-like components reflect within-client processes of change, and may highlight active ingredients of successful treatment. Distinguishing between the two is essential for clarifying the underlying processes of change in psychotherapy, and ultimately identifying empirically-derived individualized treatment targets. We review studies that implement methodological and statistical approaches for disentangling the two. These studies clarified particular mechanisms of change that may operate in a given treatment, highlighted differences in the processes of change between different treatments, and explored the within-individual interplay between different mechanisms of change during treatment. Examples include studies investigating the therapeutic role of behavioral, cognitive, and interpersonal skills, as well as emotional processing. We conclude with suggestions for future research, including attention to diversity, improved measurement to facilitate a reliable and valid estimation of trait-like and state-like components, the use of appropriate statistical approaches to adequately disentangle the two components, integration of theory-driven and data-driven methods of analysis, and the need to experimentally manipulate the state-like changes in a given mechanism of change to strengthen causal inferences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zilcha-Mano and Webb.)

Background: Approximately half of depressed adolescents fail to respond to cognitive behavioral therapy (CBT). Given the variability in response, it is important to identify pretreatment characteristics that predict prognosis. Knowledge of which depressed adolescents are likely to exhibit a positive versus poor outcome to CBT may have important clinical implications (e.g., informing treatment recommendations). Emerging evidence suggests that neural reward responsiveness represents one promising predictor., Methods: Adolescents with major depressive disorder (n = 36) received CBT and completed a reward task at 3 time points (pretreatment, midtreatment and posttreatment) while 128-channel electroencephalographic data were acquired. Healthy control participants (n = 29) completed the same task at 3 corresponding time points. Analyses focused on event-related potentials linked to 2 stages of neural processing: initial response to rewards (reward positivity) and later, elaborative processing (late positive potential). Moreover, time-frequency analyses decomposed the reward positivity into 2 constituent components: reward-related delta and loss-related theta activity., Results: Multilevel modeling revealed that greater pretreatment reward responsiveness, as measured by the late positive potential to rewards, predicted greater depressive symptom change. In addition, a group × condition × time interaction emerged for theta activity to losses, reflecting normalization of theta power in the group with major depressive disorder from baseline to posttreatment., Conclusions: An event-related potential measure of sustained (late positive potential)-but not initial (reward positivity)-reward responsiveness predicted symptom improvement, which may help inform which depressed adolescents are most likely to benefit from CBT. In addition to alleviating depression, successful CBT may attenuate underlying neural (theta) hypersensitivity to negative outcomes in depressed youths., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Although many studies have examined potential moderators of the relation between nightmares and suicide, few have examined emotion regulation, particularly utilizing severe populations such as psychiatric inpatients. The present study sought to investigate whether emotion regulation difficulties are associated with nightmares and suicide attempts in an inpatient sample. We included 2,683 psychiatric inpatients ranging from 18 to 81 years (M = 34.35, SD = 14.70). Nightmare frequency, emotion regulation difficulties, and their interaction predicted previous suicide attempts. Limitations include the homogeneity and cross-sectional nature of the sample. Suggestions for future study are discussed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Standard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non-selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse., Methods: In a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1. Individuals who responded continued on another 8-week course of the same intervention in stage 2, while sertraline and placebo nonresponders crossed over to bupropion and sertraline, respectively. Data from 241 participants were analyzed. The stage 2 sample comprised 87 patients with major depressive disorder who switched medication and 38 healthy control subjects. A total of 116 participants with major depressive disorder treated with sertraline in stage 1 served as an independent replication sample. The probabilistic reward task and resting-state functional magnetic resonance imaging were administered at baseline., Results: Greater pretreatment reward sensitivity and higher resting-state functional connectivity between bilateral nucleus accumbens and rostral anterior cingulate cortex were associated with positive response to bupropion but not sertraline. Null findings for sertraline were replicated in the stage 1 sample., Conclusions: Pretreatment reward sensitivity and frontostriatal connectivity may identify patients likely to benefit from bupropion following selective serotonin reuptake inhibitor failures. Results call for a prospective replication based on these biomarkers to advance clinical care., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Even though the early alliance has been shown to robustly predict posttreatment outcomes, the question whether alliance leads to symptom reduction or symptom reduction leads to a better alliance remains unresolved. To better understand the relation between alliance and symptoms early in therapy, we meta-analyzed the lagged session-by-session within-patient effects of alliance and symptoms from Sessions 1 to 7., Method: We applied a 2-stage individual participant data meta-analytic approach. Based on the data sets of 17 primary studies from 9 countries that comprised 5,350 participants, we first calculated standardized session-by-session within-patient coefficients. Second, we meta-analyzed these coefficients by using random-effects models to calculate omnibus effects across the studies., Results: In line with previous meta-analyses, we found that early alliance predicted posttreatment outcome. We identified significant reciprocal within-patient effects between alliance and symptoms within the first 7 sessions. Cross-level interactions indicated that higher alliances and lower symptoms positively impacted the relation between alliance and symptoms in the subsequent session., Conclusion: The findings provide empirical evidence that in the early phase of therapy, symptoms and alliance were reciprocally related to one other, often resulting in a positive upward spiral of higher alliance/lower symptoms that predicted higher alliances/lower symptoms in the subsequent sessions. Two-stage individual participant data meta-analyses have the potential to move the field forward by generating and interlinking well-replicable process-based knowledge. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Cognitive deficits in depressed adults may reflect impaired decision-making. To investigate this possibility, we analyzed data from unmedicated adults with Major Depressive Disorder (MDD) and healthy controls as they performed a probabilistic reward task. The Hierarchical Drift Diffusion Model (HDDM) was used to quantify decision-making mechanisms recruited by the task, to determine if any such mechanism was disrupted by depression., Methods: Data came from two samples (Study 1: 258 MDD, 36 controls; Study 2: 23 MDD, 25 controls). On each trial, participants indicated which of two similar stimuli was presented; correct identifications were rewarded. Quantile-probability plots and the HDDM quantified the impact of MDD on response times (RT), speed of evidence accumulation (drift rate), and the width of decision thresholds, among other parameters., Results: RTs were more positively skewed in depressed v. healthy adults, and the HDDM revealed that drift rates were reduced-and decision thresholds were wider-in the MDD groups. This pattern suggests that depressed adults accumulated the evidence needed to make decisions more slowly than controls did., Conclusions: Depressed adults responded slower than controls in both studies, and poorer performance led the MDD group to receive fewer rewards than controls in Study 1. These results did not reflect a sensorimotor deficit but were instead due to sluggish evidence accumulation. Thus, slowed decision-making-not slowed perception or response execution-caused the performance deficit in MDD. If these results generalize to other tasks, they may help explain the broad cognitive deficits seen in depression.

Despite advancements in medical and interventional therapy, patients with cardiovascular disease (CVD) continue to have residual risk for recurrent cardiovascular events. Colchicine has a unique antiinflammatory mechanism that has generated interest in its potential use as a secondary cardiovascular preventive therapy. The objective of this systematic review was to evaluate the evidence for long-term (6 months or more) colchicine therapy in patients with established CVD. A search of Medline and Embase from inception to February 2020 was performed. Included were randomized controlled trials (RCTs) or propensity score-matched observational studies that compared colchicine (at any dose) with placebo or no treatment. Outcomes of interest included any major adverse cardiovascular event, cardiovascular hospitalization, coronary artery restenosis, cardiovascular death, or all-cause death. Five RCTs were included. The dose of colchicine ranged from 0.5 mg/day to 0.6 mg twice/day, and follow-up ranged from ~6-36 months. Two trials (one double blind and one single blind) showed a reduction in composite outcomes of major adverse cardiovascular events. One study failed to demonstrate a benefit with colchicine in restenosis or recurrent ischemia after angioplasty; however, it was conducted before the routine use of modern percutaneous coronary intervention and medical therapies. In contrast, a more recent trial found that colchicine reduced the rate of in-stent restenosis in patients who received a bare metal stent. Finally, one trial in patients with heart failure with reduced ejection fraction did not observe a benefit in death or heart failure hospitalization with colchicine despite a reduction in inflammatory markers. No trial demonstrated a reduction in cardiovascular or all-cause death, and most trials showed an increase in the rate of diarrhea with colchicine. Overall, colchicine has demonstrated promising results for the secondary prevention of CVD; however, further studies are required to confirm these findings before colchicine can be routinely recommended in practice., (© 2020 Pharmacotherapy Publications, Inc.)

Objective: Research on predictors of treatment outcome in depression has largely derived from randomized clinical trials involving strict standardization of treatments, stringent patient exclusion criteria, and careful selection and supervision of study clinicians. The extent to which findings from such studies generalize to naturalistic psychiatric settings is unclear. This study sought to predict depression outcomes for patients seeking treatment within an intensive psychiatric hospital setting and while comparing the performance of a range of machine learning approaches., Method: Depressed patients (N = 484; ages 18-72; 89% White) receiving treatment within a psychiatric partial hospital program delivering pharmacotherapy and cognitive behavioral therapy were split into a training sample and holdout sample. First, within the training sample, 51 pretreatment variables were submitted to 13 machine learning algorithms to predict, via cross-validation, posttreatment Patient Health Questionnaire-9 depression scores. Second, the best performing modeling approach (lowest mean squared error; MSE) from the training sample was selected to predict outcome in the holdout sample., Results: The best performing model in the training sample was elastic net regularization (ENR; MSE = 20.49, R2 = .28), which had comparable performance in the holdout sample (MSE = 11.26; R2 = .38). There were 14 pretreatment variables that predicted outcome. To demonstrate the translation of an ENR model to personalized prediction of treatment outcome, a patient-specific prognosis calculator is presented., Conclusions: Informed by pretreatment patient characteristics, such predictive models could be used to communicate prognosis to clinicians and to guide treatment planning. Identified predictors of poor prognosis may suggest important targets for intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Outpatient total joint home recovery (HR) is a rapidly growing initiative being developed and employed at high volume orthopedic centers. Minimally invasive surgery, improved pain control and home health services have made HR possible. Multidisciplinary teams with members ranging from surgeons and anesthesiologists to hospital administrators, physical therapists, nurses and research analysts are necessary for success. Eligibility criteria for outpatient total joint arthroplasty will vary between medical centers. Surgeon preference in addition to medical comorbidities, social support, preoperative patient mobility and safety of the HR location are all factors to consider when selecting patients for outpatient total joint HR. As additional knowledge is gained, the next steps will be to establish 'best practices' and speciality society-endorsed guidelines for patients undergoing outpatient total joint arthroplasty.

A major goal for the revision of the International Classification of Diseases and Related Health Problems, Tenth Edition (ICD-10) is to increase the clinical utility of the diagnostic system. Schizoaffective disorder has a history of poor diagnostic reliability due to the similarities and overlap in symptoms that it shares with other disorders, especially primary psychotic and mood disorders. The present study was part of the case-controlled field trials for ICD-11 and examines how the proposed changes for schizoaffective disorder may improve differential diagnosis and diagnostic accuracy. Clinicians from around the globe (n = 873) were provided with either ICD-10 or ICD-11 diagnostic guidelines and asked to apply them to case vignettes comparing schizoaffective disorder to schizophrenia and mood disorders with psychotic symptoms. Participants were asked to respond to follow-up diagnostic questions to determine which components of the diagnostic guidelines affected diagnostic accuracy. Overall, clinicians showed small improvements in accurately diagnosing vignettes using ICD-11 over ICD-10. Results suggest the discrepancy in diagnosing schizoaffective disorder is related primarily to the presence of mood symptoms and discrepancies about whether those symptoms are more consistent with schizoaffective disorder or a mood disorder diagnosis. Continuing to identify ways to more accurately capture this symptom picture will be important in the future as well as systematic efforts to educate clinicians about differential diagnosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)