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This study examines the relationship between self-reported and physiologically measured sleep quality and their impact on neurocognitive performance in individuals with depression. Using data from 249 participants with medium to severe depression monitored over 13 weeks, sleep quality was assessed via retrospective self-report and physiological measures from consumer smartphones and smartwatches. Correlations between self-reported and physiological sleep measures were generally weak. Machine learning models revealed that self-reported sleep quality could detect all depression symptoms measured using the Patient Health Questionnaire-14, whereas physiological sleep measures detected "sleeping too much" and low libido. Notably, only self-reported sleep disturbances correlated significantly with neurocognitive performance, specifically with processing speed. Physiological sleep was able to detect changes in self-reported sleep, medication use, and sleep latency. These findings emphasize that self-reported and physiological sleep quality are not measuring the same construct, and both are important to monitor when studying sleep quality in relation to depression., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Passive smartphone measures hold significant potential and are increasingly employed in psychological and biomedical research to capture an individual's behavior. These measures involve the near-continuous and unobtrusive collection of data from smartphones without requiring active input from participants. For example, GPS sensors are used to determine the (social) context of a person, and accelerometers to measure movement. However, utilizing passive smartphone measures presents methodological challenges during data collection and analysis. Researchers must make multiple decisions when working with such measures, which can result in different conclusions. Unfortunately, the transparency of these decision-making processes is often lacking. The implementation of open science practices is only beginning to emerge in digital phenotyping studies and varies widely across studies. Well-intentioned researchers may fail to report on some decisions due to the variety of choices that must be made. To address this issue and enhance reproducibility in digital phenotyping studies, we propose the adoption of preregistration as a way forward. Although there have been some attempts to preregister digital phenotyping studies, a template for registering such studies is currently missing. This could be problematic due to the high level of complexity that requires a well-structured template. Therefore, our objective was to develop a preregistration template that is easy to use and understandable for researchers. Additionally, we explain this template and provide resources to assist researchers in making informed decisions regarding data collection, cleaning, and analysis. Overall, we aim to make researchers' choices explicit, enhance transparency, and elevate the standards for studies utilizing passive smartphone measures., (© 2024. The Author(s).)

Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified ( N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression ( d = 0.088, p = 0.103, N = 1530) and social functioning ( d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology ( d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes ( d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v . antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.

Researchers at the Department of Veterans Affairs (VA) have studied interventions for posttraumatic stress disorder and co-occurring conditions in both traditional and digital formats. One such empirically supported intervention is web skills training in affective and interpersonal regulation (webSTAIR), a coached, 10-module web program based on STAIR. To understand which patient characteristics were predictive of webSTAIR outcomes in a sample of trauma-exposed veterans ( N = 189), we used machine learning (ML) to develop a prognostic index from among 18 baseline characteristics (i.e., demographic, military, trauma history, and clinical) to predict posttreatment posttraumatic stress disorder severity, depression severity, and psychosocial functioning impairment. We compared the ML models to a benchmark of linear regression models in which the only predictor was the baseline severity score of the outcome measure. The ML and "severity-only" models performed similarly, explaining 39%-45% of the variance in outcomes. This suggests that baseline symptom severity and functioning are strong indicators for webSTAIR outcomes in veterans, with higher severity indicating worse prognosis, and that the other variables examined did not contribute significant added predictive signal. Findings also highlight the importance of comparing ML models to an appropriate benchmark. Future research with larger samples could potentially detect smaller patient-level effects as well as effects driven by other types of variables (e.g., therapeutic process variables). As a transdiagnostic, digital intervention, webSTAIR can potentially serve a diverse veteran population with varying trauma histories and may be best conceptualized as a beneficial first step of a stepped care model for those with heightened symptoms or impairment. (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.

Understanding how and for whom cognitive-behavioral therapies work is central to the development and improvement of mental health interventions. Suboptimal quantification of the active elements of cognitive-behavioral therapies has hampered progress in elucidating mechanisms of change. To advance process research on cognitive-behavioral therapies, we describe a theoretical measurement framework that focuses on the delivery, receipt, and application of the active elements of these interventions. We then provide recommendations for measuring the active elements of cognitive-behavioral therapies aligned with this framework. Finally, to support measurement harmonization and improve study comparability, we propose the development of a publicly available repository of assessment tools: the Active Elements of Cognitive-Behavioral Therapies Measurement Kit., Competing Interests: Declaration of competing interest To the best of our knowledge, no author has a conflict of interest, financial or otherwise., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Depression is highly recurrent, even following successful pharmacological and/or psychological intervention. We aimed to develop clinical prediction models to inform adults with recurrent depression choosing between antidepressant medication (ADM) maintenance or switching to Mindfulness-Based Cognitive Therapy (MBCT). Using data from the PREVENT trial ( N =424), we constructed prognostic models using elastic net regression that combined demographic, clinical and psychological factors to predict relapse at 24 months under ADM or MBCT. Only the ADM model (discrimination performance: AUC=.68) predicted relapse better than baseline depression severity (AUC=.54; one-tailed DeLong's test: z =2.8, p =.003). Individuals with the poorest ADM prognoses who switched to MBCT had better outcomes compared to those who maintained ADM (48% vs. 70% relapse, respectively; superior survival times [ z =-2.7, p =.008]). For individuals with moderate-to-good ADM prognosis, both treatments resulted in similar likelihood of relapse. If replicated, the results suggest that predictive modeling can inform clinical decision-making around relapse prevention in recurrent depression.

Background: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data., Methods: Individual patient data from all six eligible randomised controlled trials were used to develop ( k = 3, n = 1722) and test ( k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months., Results: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact., Conclusions: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.

Background: Cognitive therapy and behavioural activation are both widely applied and effective psychotherapies for depression, but it is unclear which works best for whom. Individual participant data (IPD) meta-analysis allows for examining moderators at the participant level and can provide more precise effect estimates than conventional meta-analysis, which is based on study-level data., Aims: This article describes the protocol for a systematic review and IPD meta-analysis that aims to compare the efficacy of cognitive therapy and behavioural activation for adults with depression, and to explore moderators of treatment effect. (PROSPERO: CRD42022341602)., Method: Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library, to identify randomised clinical trials comparing cognitive therapy and behavioural activation for adult acute-phase depression. Investigators of these trials will be invited to share their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to assess treatment effects and to examine various available demographic, clinical and psychological participant characteristics as potential moderators. The primary outcome measure will be depressive symptom level at treatment completion. Secondary outcomes will include post-treatment anxiety, interpersonal functioning and quality of life, as well as follow-up outcomes., Conclusions: To the best of our knowledge, this will be the first IPD meta-analysis concerning cognitive therapy versus behavioural activation for adult depression. This study has the potential to enhance our knowledge of depression treatment by using state-of-the-art statistical techniques to compare the efficacy of two widely used psychotherapies, and by shedding more light on which of these treatments might work best for whom.

Importance: Socioeconomic factors are associated with the prevalence of depression, but their associations with prognosis are unknown. Understanding this association would aid in the clinical management of depression., Objective: To determine whether employment status, financial strain, housing status, and educational attainment inform prognosis for adults treated for depression in primary care, independent of treatment and after accounting for clinical prognostic factors., Data Sources: The Embase, International Pharmaceutical Abstracts, MEDLINE, PsycINFO, and Cochrane (CENTRAL) databases were searched from database inception to October 8, 2021., Study Selection: Inclusion criteria were as follows: randomized clinical trials that used the Revised Clinical Interview Schedule (CIS-R; the most common comprehensive screening and diagnostic measure of depressive and anxiety symptoms in primary care randomized clinical trials), measured socioeconomic factors at baseline, and sampled patients with unipolar depression who sought treatment for depression from general physicians/practitioners or who scored 12 or more points on the CIS-R. Exclusion criteria included patients with depression secondary to a personality or psychotic disorder or neurologic condition, studies of bipolar or psychotic depression, studies that included children or adolescents, and feasibility studies. Studies were independently assessed against inclusion and exclusion criteria by 2 reviewers., Data Extraction and Synthesis: Data were extracted and cleaned by data managers for each included study, further cleaned by multiple reviewers, and cross-checked by study chief investigators. Risk of bias and quality were assessed using the Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools, respectively. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses-Individual Participant Data (PRISMA-IPD) reporting guidelines., Main Outcomes and Measures: Depressive symptoms at 3 to 4 months after baseline., Results: This systematic review and individual patient data meta-analysis identified 9 eligible studies that provided individual patient data for 4864 patients (mean [SD] age, 42.5 (14.0) years; 3279 women [67.4%]). The 2-stage random-effects meta-analysis end point depressive symptom scale scores were 28% (95% CI, 20%-36%) higher for unemployed patients than for employed patients and 18% (95% CI, 6%-30%) lower for patients who were homeowners than for patients living with family or friends, in hostels, or homeless, which were equivalent to 4.2 points (95% CI, 3.6-6.2 points) and 2.9 points (95% CI, 1.1-4.9 points) on the Beck Depression Inventory II, respectively. Financial strain and educational attainment were associated with prognosis independent of treatment, but unlike employment and housing status, there was little evidence of associations after adjusting for clinical prognostic factors., Conclusions and Relevance: Results of this systematic review and meta-analysis revealed that unemployment was associated with a poor prognosis whereas home ownership was associated with improved prognosis. These differences were clinically important and independent of the type of treatment received. Interventions that address employment or housing difficulties could improve outcomes for patients with depression.

Objective: To investigate associations between major life events and prognosis independent of treatment type: (1) after adjusting for clinical prognostic factors and socio-demographics; (2) amongst patients with depressive episodes at least six-months long; and (3) patients with a first life-time depressive episode., Methods: Six RCTs of adults seeking treatment for depression in primary care met eligibility criteria, individual patient data (IPD) were collated from all six (n = 2858). Participants were randomized to any treatment and completed the same baseline assessment of life events, demographics and clinical prognostic factors. Two-stage random effects meta-analyses were conducted., Results: Reporting any major life events was associated with poorer prognosis regardless of treatment type. Controlling for baseline clinical factors, socio-demographics and social support resulted in minimal residual evidence of associations between life events and treatment prognosis. However, removing factors that might mediate the relationships between life events and outcomes reporting: arguments/disputes, problem debt, violent crime, losing one's job, and three or more life events were associated with considerably worse prognoses (percentage difference in 3-4 months depressive symptoms compared to no reported life events =30.3%(95%CI: 18.4-43.3))., Conclusions: Assessing for clinical prognostic factors, social support, and socio-demographics is likely to be more informative for prognosis than assessing self-reported recent major life events. However, clinicians might find it useful to ask about such events, and if they are still affecting the patient, consider interventions to tackle problems related to those events (e.g. employment support, mediation, or debt advice). Further investigations of the efficacy of such interventions will be important., (Copyright © 2021. Published by Elsevier B.V.)

Importance: Depression is a major cause of disability worldwide. Although empirically supported treatments are available, there is scarce evidence on how to effectively personalize psychological treatment selection., Objective: To compare the clinical effectiveness and cost-effectiveness of 2 treatment selection strategies: stepped care and stratified care., Design, Setting, and Participants: This multisite, cluster randomized clinical trial recruited participants from the English National Health Service from July 5, 2018, to February 1, 2019. Thirty clinicians working across 4 psychological therapy services were randomly assigned to provide stratified (n = 15) or stepped (n = 15) care. In stepped care, patients sequentially access low-intensity guided self-help followed by high-intensity psychotherapy. In stratified care, patients are matched with either low- or high-intensity treatments at initial assessment. Data were analyzed from May 18, 2020, to October 13, 2021, using intention-to-treat principles., Interventions: All clinicians used the same interview schedule to conduct initial assessments with patients seeking psychological treatment for common mental disorders, but those in the stratified care group received a personalized treatment recommendation for each patient generated by a machine learning algorithm. Eligible patients received either stratified or stepped care (ie, treatment as usual)., Main Outcomes and Measures: The preregistered outcome was posttreatment reliable and clinically significant improvement (RCSI) of depression symptoms (measured using the 9-item Patient Health Questionnaire). The RCSI outcome was compared between groups using logistic regression adjusted for baseline severity. Cost-effectiveness analyses compared incremental costs and health outcomes of the 2 treatment pathways., Results: A total of 951 patients were included (618 women among 950 with data available [65.1%]; mean [SD] age, 38.27 [14.53] years). The proportion of cases of RCSI was significantly higher in the stratified care arm compared with the stepped care arm (264 of 505 [52.3%] vs 134 of 297 [45.1%]; odds ratio, 1.40 [95% CI, 1.04-1.87]; P = .03). Stratified care was associated with a higher mean additional cost per patient (£104.5 [95% CI, £67.5-£141.6] [$139.83 (95% CI, $90.32-$189.48)]; P < .001) because more patients accessed high-intensity treatments (332 of 583 [56.9%] vs 107 of 368 [29.1%]; χ2 = 70.51; P < .001), but this additional cost resulted in an approximately 7% increase in the probability of RCSI., Conclusions and Relevance: In this cluster randomized clinical trial of adults with common mental disorders, stratified care was efficacious and cost-effective for the treatment of depression symptoms compared with stepped care. Stratified care can improve depression treatment outcomes at a modest additional cost., Trial Registration: isrctn.org Identifier: ISRCTN11106183.

Many individuals in need of mental health services do not currently receive care. Scalable programs are needed to reduce the burden of mental illness among those without access to existing providers. Digital interventions present an avenue for increasing the reach of mental health services. These interventions often rely on paraprofessionals, or coaches, to support the treatment. Although existing programs hold immense promise, providers must ensure that treatments are delivered with high fidelity and adherence to the treatment model. In this paper, we first highlight the tension between the scalability and fidelity of mental health services. We then describe the design and implementation of a peer-to-peer coach training program to support a digital mental health intervention for undergraduate students within a university setting. We specifically note strategies for emphasizing fidelity within our scalable framework, including principles of learning theory and competency-based supervision. Finally, we discuss future applications of this work, including the potential adaptability of our model for use within other contexts., (©Benjamin M Rosenberg, Tamar Kodish, Zachary D Cohen, Elizabeth Gong-Guy, Michelle G Craske. Originally published in JMIR Mental Health (https://mental.jmir.org), 26.01.2022.)

Background: Subgrouping methods have the potential to support treatment decision making for patients with depression. Such approaches have not been used to study the continued course of depression or likelihood of relapse following treatment., Method: Data from individual participants of seven randomised controlled trials were analysed. Latent profile analysis was used to identify subgroups based on baseline characteristics. Associations between profiles and odds of both continued chronic depression and relapse up to one year post-treatment were explored. Differences in outcomes were investigated within profiles for those treated with antidepressants, psychological therapy, and usual care., Results: Seven profiles were identified; profiles with higher symptom severity and long durations of both anxiety and depression at baseline were at higher risk of relapse and of chronic depression. Members of profile five (likely long durations of depression and anxiety, moderately-severe symptoms, and past antidepressant use) appeared to have better outcomes with psychological therapies: antidepressants vs. psychological therapies (OR (95% CI) for relapse = 2.92 (1.24-6.87), chronic course = 2.27 (1.27-4.06)) and usual care vs. psychological therapies (relapse = 2.51 (1.16-5.40), chronic course = 1.98 (1.16-3.37))., Conclusions: Profiles at greater risk of poor outcomes could benefit from more intensive treatment and frequent monitoring. Patients in profile five may benefit more from psychological therapies than other treatments.

Dropout from psychotherapy is common and can have negative effects for patients, providers, and researchers. A better understanding of when and why patients stop treatment early, as well as actionable factors contributing to dropout, has the potential to prevent it. Here, we examined dropout from a large randomized controlled trial of transdiagnostic versus single-diagnosis cognitive-behavioral treatment (CBT) for patients with anxiety disorders (n = 179; Barlow et al., 2017). We aimed to characterize the timing of and reasons for dropout and test whether participants who dropped out had different symptom trajectories than those who completed treatment. Results indicated that overall, the greatest risk of dropout was prior to the first treatment session. In single-diagnosis CBT, dropout risk was particularly elevated before the first session and after other early sessions, whereas in transdiagnostic CBT, dropout risk was low and stable before and during treatment. Participants most often dropped out due to failure to comply with study procedures or dissatisfaction with or desiring alternative treatment. Results from multilevel models showed that trajectories of anxiety symptoms did not significantly differ between dropouts and completers. These findings suggest that there may be specific time windows for targeted and timely interventions to prevent dropout from CBT., (Copyright © 2021. Published by Elsevier Ltd.)

PTSD treatment guidelines recommend several treatments with extensive empirical support, including Prolonged Exposure (PE), a trauma-focused treatment and Present-Centered Therapy (PCT), a non-trauma-focused therapy. Research to inform treatment selection has yielded inconsistent findings with single prognostic variables that are difficult to integrate into clinical decision-making. We examined whether a combination of prognostic factors can predict different benefits in a trauma-focused vs. a non-trauma-focused psychotherapy. We applied a multi-method variable selection procedure and developed a prognostic index (PI) with a sample of 267 female veterans and active-duty service members (mean age 45; SD = 9.37; 53% White) with current PTSD who began treatment in a randomized clinical trial comparing PE and PCT. We conducted linear regressions predicting outcomes (Clinician-Administered PTSD Scale score) with treatment condition, the PI, and the interaction between the PI and treatment condition. The interaction between treatment type and PI moderated treatment response, moderated post-treatment symptom severity, b = 0.30, SE b  = 0.15 [95% CI: 0.01, 0.60], p = .049. For the 64% of participants with the best prognoses, PE resulted in better post-treatment outcomes; for the remainder, there was no difference. Use of a PI may lead to optimized patient outcomes and greater confidence when selecting trauma-focused treatments., (Copyright © 2021. Published by Elsevier Ltd.)

Aims: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care., Methods: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/., Results: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders., Conclusion: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.

We present methodological advances in understanding the effectiveness of personalized medicine models and supply easy-to-use open-source software. Personalized medicine involves the systematic use of individual patient characteristics to determine which treatment option is most likely to result in a better average outcome for the patient. Why is personalized medicine not done more in practice? One of many reasons is because practitioners do not have any easy way to holistically evaluate whether their personalization procedure does better than the standard of care, termed improvement . Our software, "Personalized Treatment Evaluator" (the R package PTE), provides inference for improvement out-of-sample in many clinical scenarios. We also extend current methodology by allowing evaluation of improvement in the case where the endpoint is binary or survival. In the software, the practitioner inputs 1) data from a single-stage randomized trial with one continuous, incidence or survival endpoint and 2) an educated guess of a functional form of a model for the endpoint constructed from domain knowledge. The bootstrap is then employed on data unseen during model fitting to provide confidence intervals for the improvement for the average future patient (assuming future patients are similar to the patients in the trial). One may also test against a null scenario where the hypothesized personalization are not more useful than a standard of care. We demonstrate our method's promise on simulated data as well as on data from a randomized comparative trial investigating two treatments for depression., 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 Kapelner, Bleich, Levine, Cohen, DeRubeis and Berk.)

Background: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes., Method: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators., Results: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms., Conclusion: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

In light of the well-established relationship between posttraumatic stress disorder (PTSD) and suicidal ideation (SI), there has been a push for treatments that simultaneously improve symptoms of PTSD and decrease SI. Using data from a randomized controlled hybrid implementation-effectiveness trial, the current study investigated the effectiveness of Cognitive Processing Therapy (CPT; Resick, Monson, & Chard, 2016) on PTSD and SI. The patient sample (N = 188) was diverse in military and veteran status, gender, and comorbidity, and 73% of the sample endorsed SI at one or more points during CPT. Participants demonstrated significant improvement in SI over the course of CPT. Multilevel growth curve modeling revealed a significant association between PTSD symptom change and change in SI. Results from cross-lagged multilevel regressions indicated that PTSD symptoms predicted SI in the next session, yet SI in a given session did not predict PTSD symptoms in the next session. Potentially relevant clinical factors (i.e., military status, gender, depression diagnosis, baseline SI, study consultation condition) were not associated with the relationship between PTSD symptoms and SI. These results add to the burgeoning literature suggesting that evidence-based treatments for PTSD, like CPT, reduce suicidality in a range of individuals with PTSD, and that this reduction is predicted by improvements in PTSD symptoms., (Copyright © 2021 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Objective: Depressed patients rate social support as important for prognosis, but evidence for a prognostic effect is lacking. We aimed to test the association between social support and prognosis independent of treatment type, and the severity of depression, and other clinical features indicating a more severe illness., Methods: Individual patient data were collated from all six eligible RCTs (n = 2858) of adults seeking treatment for depression in primary care. Participants were randomized to any treatment and completed the same baseline assessment of social support and clinical severity factors. Two-stage random effects meta-analyses were conducted., Results: Social support was associated with prognosis independent of randomized treatment but effects were smaller when adjusting for depressive symptoms and durations of depression and anxiety, history of antidepressant treatment, and comorbid panic disorder: percentage decrease in depressive symptoms at 3-4 months per z-score increase in social support = -4.14(95%CI: -6.91 to -1.29). Those with a severe lack of social support had considerably worse prognoses than those with no lack of social support: increase in depressive symptoms at 3-4 months = 14.64%(4.25% to 26.06%)., Conclusions: Overall, large differences in social support pre-treatment were associated with differences in prognostic outcomes. Adding the Social Support scale to clinical assessments may be informative, but after adjusting for routinely assessed clinical prognostic factors the differences in prognosis are unlikely to be of a clinically important magnitude. Future studies might investigate more intensive treatments and more regular clinical reviews to mitigate risks of poor prognosis for those reporting a severe lack of social support., (© 2021 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care., Methods: We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted., Results: Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3-4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3-4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions., Conclusions: When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.

Background: Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, 'conventional' meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis., Aims: We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891)., Method: We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies., Conclusions: This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.

Objective: This study aims at developing a treatment selection algorithm using a combination of machine learning and statistical inference to recommend patients' optimal treatment based on their pre-treatment characteristics. Methods: A disorder-heterogeneous, naturalistic sample of N  = 1,379 outpatients treated with either cognitive behavioral therapy or psychodynamic therapy was analyzed. Based on a combination of random forest and linear regression, differential treatment response was modeled in the training data ( n  = 966) to indicate each individual's optimal treatment. A separate holdout dataset ( n  = 413) was used to evaluate personalized recommendations. Results: The difference in outcomes between patients treated with their optimal vs. non-optimal treatment was significant in the training data, but non-significant in the holdout data ( b  = -0.043, p  = .280). However, for the 50% of patients with the largest predicted benefit of receiving their optimal treatment, the average percentage of change on the BSI in the holdout data was 52.6% for their optimal and 38.4% for their non-optimal treatment ( p  = .017; d  = 0.33 [0.06, 0.61]). Conclusion: A treatment selection algorithm based on a combination of ML and statistical inference might improve treatment outcome for some, but not all outpatients and could support therapists' clinical decision-making.

Background: Psychotherapies for depression are equally effective on average, but individual responses vary widely. Outcomes can be improved by optimizing treatment selection using multivariate prediction models. A promising approach is the Personalized Advantage Index (PAI) that predicts the optimal treatment for a given individual and the magnitude of the advantage. The current study aimed to extend the PAI to long-term depression outcomes after acute-phase psychotherapy., Methods: Data come from a randomized trial comparing cognitive therapy (CT, n = 76) and interpersonal psychotherapy (IPT, n = 75) for major depressive disorder (MDD). Primary outcome was depression severity, as assessed by the BDI-II, during 17-month follow-up. First, predictors and moderators were selected from 38 pre-treatment variables using a two-step machine learning approach. Second, predictors and moderators were combined into a final model, from which PAI predictions were computed with cross-validation. Long-term PAI predictions were then compared to actual follow-up outcomes and post-treatment PAI predictions., Results: One predictor (parental alcohol abuse) and two moderators (recent life events; childhood maltreatment) were identified. Individuals assigned to their PAI-indicated treatment had lower follow-up depression severity compared to those assigned to their PAI-non-indicated treatment. This difference was significant in two subsets of the overall sample: those whose PAI score was in the upper 60%, and those whose PAI indicated CT, irrespective of magnitude. Long-term predictions did not overlap substantially with predictions for acute benefit., Conclusions: If replicated, long-term PAI predictions could enhance precision medicine by selecting the optimal treatment for a given depressed individual over the long term.

Background : Pre-treatment severity is a key indicator of prognosis for those with depression. Knowledge is limited on how best to encompass severity of disorders. A number of non-severity related factors such as social support and life events are also indicators of prognosis. It is not clear whether this holds true after adjusting for pre-treatment severity as a) a depressive symptom scale score, and b) a broader construct encompassing symptom severity and related indicators: "disorder severity". In order to investigate this, data from the individual participants of clinical trials which have measured a breadth of "disorder severity" related factors are needed. Aims : 1) To assess the association between outcomes for adults seeking treatment for depression and the severity of depression pre-treatment, considered both as i) depressive symptom severity only and ii) "disorder severity" which includes depressive symptom severity and comorbid anxiety, chronicity, history of depression, history of previous treatment, functional impairment and health-related quality of life. 2) To determine whether i) social support, ii) life events, iii) alcohol misuse, and iv) demographic factors (sex, age, ethnicity, marital status, employment status, level of educational attainment, and financial wellbeing) are prognostic indicators of outcomes, independent of baseline "disorder severity" and the type of treatment received. Methods : Databases were searched for randomised clinical trials (RCTs) that recruited adults seeking treatment for depression from their general practitioners and used the same diagnostic and screening instrument to measure severity at baseline - the Revised Clinical Interview Schedule; outcome measures could differ between studies. Chief investigators of all studies meeting inclusion criteria were contacted and individual patient data (IPD) were requested. Conclusions : In total 15 RCTs met inclusion criteria. The Dep-GP database will include the 6271 participants from the 13 studies that provided IPD. This protocol outlines how these data will be analysed. Registration : PROSPERO CRD42019129512 (01/04/2019)., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Buckman JEJ et al.)

Two core features of depression include depressed mood (heightened distress) and anhedonia (reduced pleasure). Despite their centrality to depression, studies have not examined their contribution to treatment outcomes in a randomized clinical trial providing mainstream treatments like antidepressant medications (ADM) and cognitive therapy (CT). We used baseline distress and anhedonia derived from a factor analysis of the Mood and Anxiety Symptom Questionnaire to predict remission and recovery in 433 individuals with recurrent/chronic major depressive disorder. Patients were provided with only ADM or both ADM and CT. Overall, higher baseline distress and anhedonia predicted longer times to remission within one year and recovery within three years. When controlling for treatment condition, distress improved prediction of outcomes over and above anhedonia, while anhedonia did not improve prediction of outcomes over and above distress. Interactions with treatment condition demonstrated that individuals with higher distress and anhedonia benefited from receiving CT in addition to ADM, whereas there was no added benefit of CT for individuals with lower distress and anhedonia. Assessing distress and anhedonia prior to treatment may help select patients who will benefit most from CT in addition to ADM. For the treatments and outcome measures tested, utilizing distress to guide treatment planning may yield the greatest benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00057577., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective : We use a new variable selection procedure for treatment selection which generates treatment recommendations based on pre-treatment characteristics for adults with mild-to-moderate depression deciding between cognitive behavioral (CBT) versus psychodynamic therapy (PDT). Method : Data are drawn from a randomized comparison of CBT versus PDT for depression ( N  = 167, 71% female, mean-age = 39.6). The approach combines four different statistical techniques to identify patient characteristics associated consistently with differential treatment response. Variables are combined to generate predictions indicating each individual's optimal-treatment. The average outcomes for patients who received their indicated treatment versus those who did not were compared retrospectively to estimate model utility. Results : Of 49 predictors examined, depression severity, anxiety sensitivity, extraversion, and psychological treatment-needs were included in the final model. The average post-treatment Hamilton-Depression-Rating-Scale score was 1.6 points lower (95%CI = [0.5:2.8]; d  = 0.21) for those who received their indicated-treatment compared to non-indicated. Among the 60% of patients with the strongest treatment recommendations, that advantage grew to 2.6 (95%CI = [1.4:3.7]; d  = 0.37). Conclusions : Variable selection procedures differ in their characterization of the importance of predictive variables. Attending to consistently-indicated predictors may be sensible when constructing treatment selection models. The small N and lack of separate validation sample indicate a need for prospective tests before this model is used.

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).

Background : Pre-treatment severity is a key indicator of prognosis for those with depression. Knowledge is limited on how best to encompass severity of disorders. A number of non-severity related factors such as social support and life events are also indicators of prognosis. It is not clear whether this holds true after adjusting for pre-treatment severity as a) a depressive symptom scale score, and b) a broader construct encompassing symptom severity and related indicators: "disorder severity". In order to investigate this, data from the individual participants of clinical trials which have measured a breadth of "disorder severity" related factors are needed. Aims : 1) To assess the association between outcomes for adults seeking treatment for depression and the severity of depression pre-treatment, considered both as i) depressive symptom severity only and ii) "disorder severity" which includes depressive symptom severity and comorbid anxiety, chronicity, history of depression, history of previous treatment, functional impairment and health-related quality of life. 2) To determine whether i) social support, ii) life events, iii) alcohol misuse, and iv) demographic factors (sex, age, ethnicity, marital status, employment status, level of educational attainment, and financial wellbeing) are prognostic indicators of outcomes, independent of baseline "disorder severity" and the type of treatment received. Methods : Databases were searched for randomised clinical trials (RCTs) that recruited adults seeking treatment for depression from their general practitioners and used the same diagnostic and screening instrument to measure severity at baseline - the Revised Clinical Interview Schedule; outcome measures could differ between studies. Chief investigators of all studies meeting inclusion criteria were contacted and individual patient data (IPD) were requested. Conclusions : In total 15 RCTs met inclusion criteria. The Dep-GP database will include the 6271 participants from the 13 studies that provided IPD. This protocol outlines how these data will be analysed. Registration : PROSPERO CRD42019129512 (01/04/2019)., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Buckman JEJ et al.)

Objectives: Lithium and quetiapine are known to be effective treatments for bipolar disorder. However, little information is available to inform prediction of response to these medications. Machine-learning methods can identify predictors of response by examining variables simultaneously. Further evaluation of models on a test sample can estimate how well these models would generalize to other samples., Methods: Data (N = 482) were drawn from a randomized clinical trial of outpatients with bipolar I or II disorder who received adjunctive personalized treatment plus either lithium or quetiapine. Elastic net regularization (ENR) was used to generate models for lithium and quetiapine; these models were evaluated on a test set., Results: Predictions from the lithium model explained 17.4% of the variance in actual observed scores of patients who received lithium in the test set, while predictions from the quetiapine model explained 32.1% of the variance of patients that received quetiapine. Of the baseline variables selected, those with the largest parameter estimates were: severity of mania; attention-deficit/hyperactivity disorder (ADHD) comorbidity; nonsuicidal self-injurious behavior; employment; and comorbidity with each of two anxiety disorders (social phobia/society anxiety and agoraphobia). Predictive accuracy of the ENR model outperformed the simple and basic theoretical models., Conclusion: ENR is an effective approach for building optimal and generalizable models. Variables identified through this methodology can inform future research on predictors of response to lithium and quetiapine, as well as future modeling efforts of treatment choice in bipolar disorder., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits., Methods: Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics., Results: Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58)., Conclusions: A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.

The cognitive and behavioral interventions can be as efficacious as antidepressant medications and more enduring, but some patients will be more likely to respond to one than the other. Recent work has focused on developing sophisticated selection algorithms using machine-learning approaches that answer the question, "What works best for whom?" Moreover, the vast majority of people suffering from depression reside in low- and middle-income countries where access to either psychotherapy or medications is virtually nonexistent. Great strides have been made in training nonspecialist providers (known as task sharing) to overcome this gap. Finally, recent work growing out of evolutionary psychology suggests that antidepressant medications may suppress symptoms at the expense of prolonging the underlying episode so as to increase the risk of relapse whenever someone tries to stop. We address each of these developments and their cumulative implications., (Copyright © 2019. Published by Elsevier Ltd.)

Mental health researchers and clinicians have long sought answers to the question "What works for whom?" The goal of precision medicine is to provide evidence-based answers to this question. Treatment selection in depression aims to help each individual receive the treatment, among the available options, that is most likely to lead to a positive outcome for them. Although patient variables that are predictive of response to treatment have been identified, this knowledge has not yet translated into real-world treatment recommendations. The Personalized Advantage Index (PAI) and related approaches combine information obtained prior to the initiation of treatment into multivariable prediction models that can generate individualized predictions to help clinicians and patients select the right treatment. With increasing availability of advanced statistical modeling approaches, as well as novel predictive variables and big data, treatment selection models promise to contribute to improved outcomes in depression.

Background: Dropout rates for effective therapies for posttraumatic stress disorder (PTSD) can be high, especially in practice settings. Although clinicians have intuitions regarding what treatment patients may complete, there are few systematic data to drive those judgments., Methods: A multivariable model of dropout risk was constructed with randomized clinical trial data (n = 160) comparing prolonged exposure (PE) and cognitive processing therapy (CPT) for rape-induced PTSD. A two-step bootstrapped variable selection algorithm was applied to identify moderators of dropout as a function of treatment condition. Employing identified moderators in a model, fivefold cross-validation yielded estimates of dropout probability for each patient in each condition. Dropout rates between patients who did and did not receive their model-indicated treatment were compared., Results: Despite equivalent dropout rates across treatments, patients assigned to their model-indicated treatment were significantly less likely to drop out relative to patients who did not (relative risk = 0.49 [95% CI: 0.29-0.82]). Moderators included in the model were: childhood physical abuse, current relationship conflict, anger, and being a racial minority, all of which were associated with higher likelihood of dropout in PE than CPT., Conclusions: Individual differences among patients affect the likelihood they will complete a particular treatment, and clinicians can consider these moderators in treatment planning. In the future, treatment selection models could be used to increase the percentage of patients who will receive a full course of treatment, but replication and extension of such models, and consideration of how best to integrate them into routine practice, are needed., (© 2018 Wiley Periodicals, Inc.)

Introduction: Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works best for the depressed individual. In this paper, we aim to replicate a recently developed treatment selection method, using data from an RCT comparing the effects of cognitive therapy (CT) and interpersonal psychotherapy (IPT)., Methods: 134 depressed patients completed the pre- and post-treatment BDI-II assessment. First, we identified baseline predictors and moderators. Second, individual treatment recommendations were generated by combining the identified predictors and moderators in an algorithm that produces the Personalized Advantage Index (PAI), a measure of the predicted advantage in one therapy compared to the other, using standard regression analyses and the leave-one-out cross-validation approach., Results: We found five predictors (gender, employment status, anxiety, personality disorder and quality of life) and six moderators (somatic complaints, cognitive problems, paranoid symptoms, interpersonal self-sacrificing, attributional style and number of life events) of treatment outcome. The mean average PAI value was 8.9 BDI points, and 63% of the sample was predicted to have a clinically meaningful advantage in one of the therapies. Those who were randomized to their predicted optimal treatment (either CT or IPT) had an observed mean end-BDI of 11.8, while those who received their predicted non-optimal treatment had an end-BDI of 17.8 (effect size for the difference = 0.51)., Discussion: Depressed patients who were randomized to their predicted optimal treatment fared much better than those randomized to their predicted non-optimal treatment. The PAI provides a great opportunity for formal decision-making to improve individual patient outcomes in depression. Although the utility of the PAI approach will need to be evaluated in prospective research, this study promotes the development of a treatment selection approach that can be used in regular mental health care, advancing the goals of personalized medicine.

Background: Advances in personalized medicine require the identification of variables that predict differential response to treatments as well as the development and refinement of methods to transform predictive information into actionable recommendations., Objective: To illustrate and test a new method for integrating predictive information to aid in treatment selection, using data from a randomized treatment comparison., Method: Data from a trial of antidepressant medications (N = 104) versus cognitive behavioral therapy (N = 50) for Major Depressive Disorder were used to produce predictions of post-treatment scores on the Hamilton Rating Scale for Depression (HRSD) in each of the two treatments for each of the 154 patients. The patient's own data were not used in the models that yielded these predictions. Five pre-randomization variables that predicted differential response (marital status, employment status, life events, comorbid personality disorder, and prior medication trials) were included in regression models, permitting the calculation of each patient's Personalized Advantage Index (PAI), in HRSD units., Results: For 60% of the sample a clinically meaningful advantage (PAI≥3) was predicted for one of the treatments, relative to the other. When these patients were divided into those randomly assigned to their "Optimal" treatment versus those assigned to their "Non-optimal" treatment, outcomes in the former group were superior (d = 0.58, 95% CI .17-1.01)., Conclusions: This approach to treatment selection, implemented in the context of two equally effective treatments, yielded effects that, if obtained prospectively, would rival those routinely observed in comparisons of active versus control treatments.

Multivariate pattern analysis (MVPA) is a powerful tool for relating theories of cognitive function to the neural dynamics observed while people engage in cognitive tasks. Here, we use the Context Maintenance and Retrieval model of free recall (CMR; Polyn et al., 2009a) to interpret variability in the strength of task-specific patterns of distributed neural activity as participants study and recall lists of words. The CMR model describes how temporal and source-related (here, encoding task) information combine in a contextual representation that is responsible for guiding memory search. Each studied word in the free-recall paradigm is associated with one of two encoding tasks (size and animacy) that have distinct neural representations during encoding. We find evidence for the context retrieval hypothesis central to the CMR model: Task-specific patterns of neural activity are reactivated during memory search, as the participant recalls an item previously associated with a particular task. Furthermore, we find that the fidelity of these task representations during study is related to task-shifting, the serial position of the studied item, and variability in the magnitude of the recency effect across participants. The CMR model suggests that these effects may be related to a central parameter of the model that controls the rate that an internal contextual representation integrates information from the surrounding environment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)