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Joseph M Trombello,1 Alexandra Kulikova,2 Taryn L Mayes,1 Karabi Nandy,1,3 Thomas Carmody,1,3 Gavin Bart,4 Edward V Nunes,5 Joy Schmitz,6 Mariah Kalmin,7 Steven Shoptaw,7 Madhukar H Trivedi1 1Center for Depression Research and Clinical Care, Peter O’Donnell Jr. Brain Institute and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Department of Educational Psychology, University of North Texas, Denton, TX, USA; 3Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Department of Medicine, University of Minnesota, Hennepin County Medical Center, Minneapolis, MN, USA; 5Department of Psychiatry, Columbia University Irving Medical Center and New York State Psychiatric Institute, New York, NY, USA; 6Faillace Department of Psychiatry and Behavioral Sciences, University of Texas (UT Health) at Houston, Houston, TX, USA; 7Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USACorrespondence: Madhukar H Trivedi, Center for Depression Research and Clinical Care, Peter O’Donnell Jr. Brain Institute and Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9119, USA, Tel +214-648-0188, Fax +214-648-0167, Email Madhukar.Trivedi@utsouthwestern.eduBackground: The co-occurrence of suicidality and substance use disorders has been well established, but rating scales to examine suicidal behavior and risk are sparse among participants with substance use disorders. We examined the psychometric properties of the 16-item Concise Health Risk Tracking Scale – Self Report (CHRT-SR16) to measure suicidality among adults with moderate-to-severe methamphetamine use disorder.Methods: Participants (n = 403) with moderate-to-severe methamphetamine use disorder completed the CHRT-SR16 as part of a randomized, double-blind, placebo-controlled pharmacotherapy trial. The CHRT-SR16 factor structure was assessed using confirmatory factor analysis (CFA). Internal consistency was estimated with coefficients alpha (α) and omega (ω), test-retest reliability with intraclass correlation coefficient (ICC) and standard error of measurement, and convergent validity using Spearman’s ρ rank order correlation coefficient test between CHRT-SR16 factors and the Patient Health Questionnaire (PHQ-9). The analyses utilized baseline and week 1 data (for test-retest reliability only).Results: CFA revealed a seven-factor model of Pessimism, Helplessness, Social Support, Despair, Impulsivity, Irritability, and Suicidal Thoughts as the best-fitting model. The CHRT-SR16 also exhibited strong internal consistency (α = 0.89; ω = 0.89), test-retest reliability (ICC = 0.78) and convergent validity with the PHQ-9 total score (ρ = 0.62).Conclusion: The CHRT-SR16 showed strong psychometric properties in a sample of participants with primary methamphetamine use disorder.Clinicaltrials.gov Identifier: NCT03078075.Keywords: stimulant use disorder, confirmatory factor analysis, irritability, impulsivity, propensity, PHQ-9

Background: Physical activity has the potential to improve physical and mental health outcomes of persons with depression. However, feasible and acceptable strategies to integrate physical activity interventions into real-world settings are needed., Objective: To assess the feasibility and acceptability of a manualized Behavioral Activation intervention aimed to increase physical activity in persons with depression (defined as a PHQ-9 score ≥ 10)., Methods: A single-arm pilot study was conducted. The intervention consisted of 8 tele-therapy sessions delivered over a 10-week period. Measures of feasibility included screening, enrollment, intervention adherence, outcome data availability, and intervention fidelity. Acceptability was assessed with a post-intervention survey and qualitatively through focus groups and interviews. Preliminary efficacy of the intervention was assessed by evaluating pre-to-post changes in physical activity and depressive symptoms., Results: All feasibility metrics exceeded predetermined feasibility goal metrics with the exception of Fitbit wear and screening rate, which was due to a greater than anticipated enrollment rate. Participants (n = 15) reported perceived benefits from the intervention and convenience in attending tele-therapy sessions. Depressive symptoms, as measured by the PHQ-9 improved (16.8 at enrollment to 10.1 post intervention, Cohen's d = 1.13). Self-reported moderate-to-vigorous physical activity (MVPA) increased from 22.0 min/week at baseline to 36.67 min/week post-intervention (d = 0.58). Physical activity as measured by the Fitbit showed little change (daily step 5543.29 during Week 1 to 6177.48 during Week 10, (d = 0.14); MVPA 21.23 min/week during Week 1 to 19.22 at Week 10 (d = 0.0.06)., Conclusions: Results of the pilot study suggest the intervention is feasible to deliver and acceptable to participants. Preliminary results suggest the intervention may be effective in improving depressive symptoms and increasing self-reported physical activity., Trial Registration: ClinicalTrials.gov NCT04990401, Registered July 21, 2021., (© 2024. The Author(s).)

Introduction: The ability for people living with stimulant use disorder to live meaningful lives requires not only abstinence from addictive substances, but also healthy engagement with their community, lifestyle practices, and overall health. The Treatment Effectiveness Assessment (TEA) assesses components of recovery consisting of four functional domains: substance use, health, lifestyle, and community. This secondary data analysis of 403 participants with severe methamphetamine use disorder tested the reliability and validity of the TEA., Methods: Participants were enrolled in the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for methamphetamine use disorder. The study used total TEA and domain scores at baseline to assess factor structure and internal consistency, as well as construct validity related to substance cravings (visual analog scale [VAS]), quality of life (quality-of-life assessment [QoL]), mental health (Patient Health Questionnaire-9 [PHQ-9], Concise Health Risk Tracking Scale Self-Report [CHRT-SR 16 ]), and social support (CHRT-SR 16 )., Results: Individual TEA items showed moderate to large correlations with each other (r = 0.27-0.51; p < .001), and strong correlations to the total score (r = 0.69-0.78; p < .001). Internal consistency was strong (coefficient α = 0.73 [0.68-0.77]; coefficient ω = 0.73 [0.69-0.78]). Construct validity was acceptable, with the strongest correlation between the TEA Health item and the general health status item on the QoL (r = 0.53, p < .001)., Conclusions: TEA has acceptable levels of reliability and validity supporting prior similar findings in a sample of participants with moderate to severe methamphetamine use disorder. Results from this study provide support for its use in assessing clinically meaningful changes beyond simply reduced substance use., Competing Interests: Declaration of competing interest In the last 36 months, Dr. Carmody has served as a consultant for Alkermes. Dr. Trombello was a paid consultant for Alto Neuroscience; and currently owns stock in Merck. Dr. Shoptaw has served as a consultant or advisor for Alkermes, Inc., Gilead Services, Inc., and Indivior, Inc. Dr. Trivedi has served as a consultant or advisor for Acadia Pharmaceuticals Inc., Akili Interactive, Alkermes Inc., Allergan Sales LLC, Alto Neuroscience, Inc., Applied Clinical Intelligence, LLC (ACI), Axome Therapeutics, Boehringer Ingelheim, Engage Health Media, Gh Research, GreenLight VitalSign6, Inc., Heading Health, Inc., Health Care Global Village, Janssen – Cilag.SA, Janssen Research and Development, LLC (Adv Committee Esketamine), Janssen Research and Development, LLC (panel for study design for MDD relapse), Janssen - ORBIT, Legion Health, Jazz Pharmaceuticals, LUNDBECK RESEARCH U.S.A, Medscape, LLC, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc., Myriad Neuroscience, Neurocrine Biosciences Inc., Navitor, Pharmaceuticals, Inc., Noema Pharma AG, Orexo US Inc., Otsuka Pharmaceutical Development & Commercialization, Inc. (PsychU, MDD Section Advisor), Otsuka America Pharmaceutical, Inc. (MDD expert), Pax Neuroscience, Perception Neuroscience Holdings, Inc., Pharmerit International, LP, Policy Analysis Inc., Sage, Therapeutics, Rexahn Pharmaceuticals, Inc., Sage Therapeutics, Signant Health, SK Life Science, Inc., Takeda Development Center Americas, Inc., The Baldwin Group, Inc., and Titan Pharmaceuticals, Inc. Dr. Trivedi also received editorial compensation from Oxford University Press. Other authors have no conflicts to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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: The co-occurrence of suicidality and substance use disorders has been well established, but rating scales to examine suicidal behavior and risk are sparse among participants with substance use disorders. We examined the psychometric properties of the 16-item Concise Health Risk Tracking Scale - Self Report (CHRT-SR 16 ) to measure suicidality among adults with moderate-to-severe methamphetamine use disorder., Methods: Participants (n = 403) with moderate-to-severe methamphetamine use disorder completed the CHRT-SR 16 as part of a randomized, double-blind, placebo-controlled pharmacotherapy trial. The CHRT-SR 16 factor structure was assessed using confirmatory factor analysis (CFA). Internal consistency was estimated with coefficients alpha (α) and omega (ω), test-retest reliability with intraclass correlation coefficient (ICC) and standard error of measurement, and convergent validity using Spearman's ρ rank order correlation coefficient test between CHRT-SR 16 factors and the Patient Health Questionnaire (PHQ-9). The analyses utilized baseline and week 1 data (for test-retest reliability only)., Results: CFA revealed a seven-factor model of Pessimism, Helplessness, Social Support, Despair, Impulsivity, Irritability, and Suicidal Thoughts as the best-fitting model. The CHRT-SR 16 also exhibited strong internal consistency (α = 0.89; ω = 0.89), test-retest reliability (ICC = 0.78) and convergent validity with the PHQ-9 total score ( ρ = 0.62)., Conclusion: The CHRT-SR 16 showed strong psychometric properties in a sample of participants with primary methamphetamine use disorder., Clinicaltrialsgov Identifier: NCT03078075., Competing Interests: Dr. Trombello reports owning stock in Merck and has served as a paid consultant for Alto Neuroscience LLC. He is currently a Clinical Assistant Professor of Psychiatry at UT Southwestern Medicine and was employed as an Assistant Professor of Psychiatry when the study was conducted. He is now employed by Janssen Research and Development. Dr. Carmody has served as a consultant for Alkermes, Inc. Dr. Bart reported receiving grants from the National Institute on Drug Abuse and National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study, and personal fees from the American Academy of Addiction Psychiatry in honoraria for content expertise for ongoing participation in PCSS (Providers Clinical Support System) Exchange, an educational webinar series for opioid use disorder education. Dr. Nunes has served as a consultant without compensation for Alkermes, Pear Therapeutics, and Camurus. He has been/currently serves as an investigator on NIH funded studies that received in-kind donation of medication from Alkermes, Indivior, and Braeburn, and in-kind donations of digital therapeutics from Pear Therapeutics and CHESS Health. Dr. Shoptaw has received clinical research supplies from Gilead Sciences, Inc., Alkermes, Inc., and Indivior, Inc., and has consulted for Aelis Farma, Inc., and Sparian Biosciences, Inc. Dr. Trivedi has served as a consultant or advisor for Acadia Pharmaceuticals, Inc., Akili Interactive, Alkermes, Inc. (Pub Steering Comm-ALKS5461), Allergan Sales LLC, Alto Neuroscience, Inc., Applied Clinical Intelligence, LLC (ACI), Axome Therapeutics, Boehringer Ingelheim, Engage Health Media, Gh Research, GreenLight VitalSign6, Inc., Heading Health, Inc., Health Care Global Village, Janssen – Cilag.SA, Janssen Research and Development, LLC (Adv Committee Esketamine), Janssen Research and Development, LLC (panel for study design for MDD relapse), Janssen - ORBIT, Legion Health, Jazz Pharmaceuticals, Lundbeck Research U.S.A, Medscape, LLC, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc., Myriad Neuroscience, Neurocrine Biosciences Inc, Navitor, Pharmaceuticals, Inc., Noema Pharma AG, Orexo US Inc., Otsuka Pharmaceutical Development & Commercialization, Inc. (PsychU, MDD Section Advisor), Otsuka America Pharmaceutical, Inc. (MDD expert), Pax Neuroscience, Perception Neuroscience Holdings, Inc., Pharmerit International, LP, Policy Analysis Inc., Sage, Therapeutics, Rexahn Pharmaceuticals, Inc., Sage Therapeutics, Signant Health, SK Life Science, Inc., Takeda Development Center Americas, Inc., The Baldwin Group, Inc., and Titan Pharmaceuticals, Inc. Dr. Trivedi also received editorial compensation from Oxford University Press. The other authors report no conflicts of interest in this work., (© 2023 Trombello et al.)

Introduction: Suicide prevention research is a national priority, and national guidance includes the development of suicide risk management protocols (SRMPs) for the assessment and management of suicidal ideation and behavior in research trials. Few published studies describe how researchers develop and implement SRMPs or articulate what constitutes an acceptable and effective SRMP., Methods: The Texas Youth Depression and Suicide Research Network (TX-YDSRN) was developed with the goal of evaluating screening and measurement-based care in Texas youth with depression or suicidality (i.e., suicidal ideation and/or suicidal behavior). The SRMP was developed for TX-YDSRN through a collaborative, iterative process, consistent with a Learning Healthcare System model., Results: The final SMRP included training, educational resources for research staff, educational resources for research participants, risk assessment and management strategies, and clinical and research oversight., Conclusion: The TX-YDSRN SRMP is one methodology for addressing youth participant suicide risk. The development and testing of standard methodologies with a focus on participant safety is an important next step to further the field of suicide prevention research., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Within the past 12 months, Dr. Trivedi has provided consulting services to Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc, Compass Pathfinder Limited, Daiichi Sankyo Inc, GH Research Limited, Heading Health Inc, Janssen, Legion Health Inc, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc, Merck Sharp & Dhome LLC, Naki Health, Ltd., Neurocrine Biosciences Inc, Otsuka American Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Praxis Precision Medicines Inc, Relmada Therapeutics, Inc, SAGE Therapeutics, Signant Health, Sparian Biosciences Inc, Takeda Pharmaceutical Company Ltd, and WebMD. He sits on the Scientific Advisory Board of Alto Neuroscience Inc, Cerebral Inc., Compass Pathfinder Limited, Heading Health, GreenLight VitalSign6 Inc, Legion Health Inc, and Merck Sharp & Dohme Corp. He holds stock in Alto Neuroscience Inc, Cerebral Inc, Circular Genomics Inc, GreenLight VitalSign6 Inc, Legion Health Inc. Additionally, he has received editorial compensation from American Psychiatric Association, and Oxford University Press., (© 2023 The Authors. Published by Elsevier Inc.)

Background: Poor treatment outcomes, disease recurrence, and medical co-morbidities contribute to the significant burden caused by depressive disorders. Increasing physical activity in persons with depression has the potential to improve both depression treatment outcomes and physical health. However, evidence for physical activity interventions that can be delivered as part of depression treatment remains limited. This study will examine a Behavioral Activation teletherapy intervention adapted to include a specific focus on increasing physical activity., Methods: The two-phase study will include a preliminary pilot study (n = 15) to evaluate and refine the manualized intervention using a mixed-methods approach followed by a single-arm study to evaluate feasibility and preliminary efficacy of the adapted BA teletherapy. Participants will be adults, age 18-64, with moderate to severe depressive symptoms (defined as a PHQ-9 score ≥10) and who currently engage in 90 min or less of moderate-to-vigorous physical activity. Individuals will be excluded if they have a current or past manic or hypomanic episode, psychosis, schizophrenia or schizophreniform disorder, or active suicidal ideation, or if not medically-cleared to exercise. The BA intervention will consist of 8 weekly sessions, followed by 2 bi-weekly booster sessions. Feasibility outcomes will include metrics of screening, enrollment, intervention adherence and fidelity, and participant retention. Intervention preliminary efficacy will be evaluated through assessment of changes in depressive symptoms and moderate-to-vigorous physical activity., Conclusion: Data from this trial will be used to support the conduct of a randomized controlled trial to evaluate the efficacy of the adapted BA intervention., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph Trombello is a shareholder in Merck, unrelated to the current project. Within the past 36 months, Dr. Trivedi has provided consulting services to ACADIA Pharmaceuticals, Allergan, Alkermes Inc., Alto Neuroscience Inc, Applied Clinical Intelligence, LLC, Axsome Therapeutics, Biogen MA Inc, Boegringer Ingelheim, Cerebral Inc., Circular Genomics Inc., Compass Pathfinder Limited, GH Research, GreenLight VitalSign6 Inc, Heading Health, Health Care Global Village, Janssen Pharmaceutical, Jazz Pharmaceutical, Legion Health, Lundbeck Research USA, Merck Sharp & Dohme Corp., Mind Medicine Inc., Myriad Neuroscience, Naki Health Ltd, Navitor, Neurocrine Biosciences Inc., Noema Pharma AG, Orexo US Inc., Otsuka America Pharmaceutical Inc, Perception Neuroscience Holdings, Pharmerit International, Policy Analysis Inc., Praxis Precision Medicines Inc, Rexahn Pharmaceuticals, Inc., SAGE Therapeutics, Signant Health, Sparian Biosciences, Titan Pharmaceuticals, Takeda Pharmaceuticals Inc, WebMD. He has received grant/research funding from 10.13039/100000025NIMH, NIDA, 10.13039/100006108NCATS, 10.13039/100001455American Foundation for Suicide Prevention, 10.13039/100006093Patient-Centered Outcomes Research Institute (PCORI), and Blue Cross Blue Shield of Texas. Additionally, he has received editorial compensation from Engage Health Media, and Oxford University Press. All other authors have no competing interests to report., (© 2023 Published by Elsevier Inc.)

Objective: Burnout in academic medicine has been widely studied, but most work has been conducted among physicians. Psychologists in academic medicine have unique burnout factors. Therefore, investigating the prevalence and predictors of burnout among psychologists in academic medicine during the COVID-19 pandemic represents an important addition to the literature., Methods: Sixty-two psychologists responded to burnout-related items in a larger, 40-item Psychiatry Department climate survey conducted from October to November 2020. Five items from the MINI-Z survey were administered to examine control over workload and sufficiency of documentation time as predictors of both continuous and dichotomously defined burnout. Linear and logistic regression was employed with years as a faculty member entered as a covariate., Results: Slightly less than half (48.4%) of respondents met dichotomous criteria for burnout. Faculty with fewer years of experience scored higher on their level of continuous burnout. Both control over workload and sufficiency of time for documentation were independent predictors of continuous burnout, but only control over workload remained a statistically significant predictor in a simultaneous model. Control over workload was a significant predictor in dichotomous models but did not remain so once sufficiency of documentation time was also added., Conclusion: Burnout prevalence among psychologists was comparable to rates among physicians at other institutions, even when examined during the COVID-19 pandemic. Academic medicine administrators and organizational leaders should consider policies and programming to increase control over workload, especially among junior psychologist faculty., (© 2021. Academic Psychiatry.)

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.)

Background: Anxiety disorders in youth are frequently underdiagnosed and untreated, partly due to a lack of screening in primary care. The Generalized Anxiety Disorder 7-item (GAD-7) scale is a brief self-report measure designed to screen for anxiety in primary care settings. However, little is known about the psychometrics of this scale with adolescents., Methods: Participants included 579 youth age 11 to 17 years who received screening for depression in a primary care setting through a web-based application, VitalSign 6 , over a 4-year period. Psychometric analyses were completed based on classical test theory (CTT) and item response theory (IRT)., Results: Using CTT and IRT methods, the GAD-7 has a unidimensional structure with good psychometric properties. In addition, the IRT analysis demonstrates that items 1 and 2 are strongly associated with the total score, and thus are good choices as a 2-item screening tool. Convergent validity was demonstrated, with high correlations between the GAD-7 and other measures of anxiety, and discriminant validity was also demonstrated, with low correlations to measures of other psychological states., Conclusions: This psychometric evaluation of the GAD-7 provides support for the utility of this measure with adolescents. The GAD-2 is a good estimate of GAD-7 total score.

Depression disproportionately affects patients with kidney disease, including those with nondialysis chronic kidney disease, end-stage kidney disease requiring dialysis, and kidney transplant recipients. Patients across the spectrum of kidney disease should be screened for depression every 6 to 12 months using self-report questionnaires, followed by an interview with a clinician to confirm the presence of sadness or anhedonia when depressive symptoms are identified. Pharmacologic treatment with selective serotonin reuptake inhibitors has not consistently shown benefit compared with placebo and may be associated with serious adverse outcomes including cardiovascular events, bleeding, and fractures. However, based on the availability of alternative therapies, a watchful trial with close monitoring for therapeutic and adverse effects is reasonable. Several clinical trials have suggested that cognitive behavioral therapy and physical activity improve depressive symptoms when compared with a control group. Given the low risk associated with these therapies, they should be recommended to patients who have access and are amenable to such interventions. Future trials are needed to study therapeutic options for depression in nondialysis chronic kidney disease, peritoneal dialysis, or kidney transplant recipients, as well as alternative pharmacologic therapy and combination therapies. Given improvement in depressive symptoms with placebo in existing trials, inclusion of a control group is paramount., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.)

Background: This report tests the association of self-reported symptoms of irritability with overt behavior of anger attacks (uncharacteristic sudden bouts of anger that are disproportionate to situation and associated with autonomic activation)., Methods: Participants of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care study who completed Massachusetts General Hospital Anger Attacks questionnaire were included ( n = 293). At each visit, the 17-item Hamilton Depression Rating Scale and the 16-item Concise Associated Symptom Tracking scale were used to measure depression, anxiety, and irritability. In those with anger attacks present v. those without anger attacks, separate t tests and mixed model analyses compared afore-mentioned symptoms at baseline and changes with treatment respectively. As anger attacks may occur without aggressive behaviors, analyses were repeated based only on the presence of aggressive behaviors., Results: At baseline, those with anger attacks ( n = 109) v. those without anger attacks ( n = 184) had similar levels of depression but higher levels of irritability [effect size ( d ) = 0.80] and anxiety ( d = 0.32). With acute-phase treatment, participants with anger attacks experienced a greater reduction in irritability ( p < 0.001) but not in depression ( p = 0.813) or anxiety ( p = 0.771) as compared to those without anger attacks. Yet, irritability levels at week-8 were higher in those with anger attacks ( d = 0.32) than those without anger attacks. Similar results were found in participants with aggressive behaviors., Conclusions: The presence of anger attacks in outpatients with major depressive disorder may identify a sub-group of patients with persistently elevated irritability.

Understanding the correlates of depression in HIV patients can help identify groups whose members are at increased risk for depression. We conducted a cross-sectional retrospective study among racially diverse, indigent patients living with HIV (PLWH) who were obtaining care in an urban safety-net hospital system and had completed a Patient Health Questionnaire-9 (PHQ-9) in 2014 or 2015. We collected demographics, HIV risk factors, HIV viral loads, CD4 counts, missed visits, and emergency department (ED) visits. Data from the Substance Abuse and Mental Illness Symptoms Screener (SAMISS) were abstracted. Missing data on substance use and CD4 cell counts were imputed to examine the odds of depression (PHQ-9 ≥ 10) by multivariable analysis for a complete case and sensitivity analysis. Stratified analysis by HIV viral suppression (VS) was used to determine the odds of depression among subgroups. Of the 5126 HIV patients (70.8% male,56.3% Black, 44.6% MSM, 6.0% IDU), 1271 (24.8%) experienced depression (PHQ ≥ 10). In a multivariable logistic model female gender, White race, injection drug use (IDU) or men who have sex with men (MSM) as an HIV risk factor, making ≥1 ED visit, having missed any HIV visit, having AIDS, and having a positive drug screen by SAMISS increased the odds for depression. Those who had achieved HIV VS or received efavirenz had lower odds of depression. Even among those with AIDS, those failing to achieve VS were at increased odds for depression, whereas those achieving VS were not. Moderate to severe depression is prevalent among PLWH. Among those with AIDS, HIV VS modifies the odds of depression.

Objective: To identify data-driven subgroups in Major Depressive Disorder (MDD) in order to elucidate underlying neural correlates and determine if these subgroups have utility in predicting response to antidepressant versus placebo., Methods: Using 27 clinical measures at baseline of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study, participants with MDD (n=244) were sub grouped using principal component (PC) analysis. Baseline-to-week-8 changes in depression severity with sertraline versus placebo were compared in these subgroups. Resting-state functional connectivity of these subgroups were compared to those of healthy controls (n=38)., Results: Eight subgroups were identified from four PCs: (PC1) severity of depression-associated symptoms, (PC2) sub-threshold mania and anhedonia, (PC3) childhood trauma, medical comorbidities, and sexual dysfunction, and (PC4) personality traits of openness and agreeableness. Participants with high childhood trauma experienced greater improvement with sertraline (Cohen's d=0.87), whereas those with either higher levels of subthreshold hypomanic symptoms (Cohen's d=0.67) or with lower levels of agreeableness and openness experienced greater improvement with placebo (Cohen's d=0.71). Participants with high childhood trauma had greater connectivity between salience and dorsal attention networks, whereas those with higher levels of subthreshold hypomanic symptoms and lower levels of agreeableness and openness had greater connectivity within limbic network and that of visual network with hippocampus and dorsal attention network., Conclusion: Assessing history of childhood trauma, presence of subthreshold hypomanic symptoms and personality traits may help to identify subgroups of patients with MDD who respond differentially to sertraline or placebo and have distinct neural signatures., (Copyright © 2020. Published by Elsevier B.V.)

While prior research has investigated trajectories of depressive symptom change throughout psychotherapy, such work has not been conducted exclusively among underserved patients receiving brief Behavioral Activation (BA) teletherapy, intervention modifications that should reduce barriers to therapy initiation and engagement. The current project used cluster analysis to determine discrete groups of symptom change among patients receiving an 8-session BA teletherapy intervention, and analyzed whether demographic and clinical characteristics were associated with group membership. Data from 105 patients referred from charity primary care clinics and receiving at least two therapy sessions were analyzed. Patients were predominantly female and Latina. The 9-item Patient Health Questionnaire (PHQ-9) was the outcome. Two categories were determined: a larger group (N = 61) demonstrating initially less severe symptoms and experiencing a gradual recovery, and a smaller group beginning with more severe symptoms, and experiencing a steeper recovery. In both groups, a majority of participants experienced at least a 5-point drop in depressive symptoms, while in the latter group, a majority of patients achieved depressive symptom remission (PHQ-9 < 5). Monolingual Spanish speakers were more likely to be in the former group, but no other demographic or clinical characteristics were associated with group membership. In both groups, a majority of the symptom reduction occurred by sessions 4-6. Therefore, two categories of depressive symptom change, slow responders and rapid responders, occur among patients receiving a brief BA teletherapy intervention. No demographic differences aside from primary language, nor any clinical characteristics, distinguish group membership, suggesting similar patterns of symptom reduction among a primarily underserved sample., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Heterogeneity in major depressive disorder (MDD) is well recognized but not well understood. Core depressive features are reward and emotional symptoms, which reflect dysfunctions in the positive valence (PV) and negative valence (NV) systems, respectively. This study assessed whether PV and NV systems (based on selected symptoms) were associated with different clinical features, antidepressant response, and levels of immunomarkers in adults with MDD., Methods: These analyses used data from combining medications to enhance depression outcomes study (N = 665; n = 166 for immunomarkers). PV and NV symptom scores were extracted from the clinician-rated 30-item Inventory of Depressive Symptomatology. Correlational analyses were conducted., Results: PV and NV symptom scores were substantially associated with different clinical features. PV symptoms (impaired motivation, impaired energy, and anhedonia) were independently associated with female gender (p < .001), older age (p = .012), and higher cognitive and physical impairment (p < .001) according to the 7-item Cognitive and Physical Functioning Questionnaire. Conversely, NV symptoms (anxiety and interpersonal sensitivity) were independently associated with younger age (p = .013), more anxious comorbidities (p = .001 for generalized anxiety disorder and p = .002 for social phobia) and other commonly associated noncriterion symptoms (p < .001). Overall, PV symptoms were more responsive to antidepressants than NV symptoms (p < .0001; Cohen's d = .455). A PV symptom score was positively correlated with the concentration of three proinflammatory and one anti-inflammatory factor. In contrast, an NV symptom score was negatively associated with only one proinflammatory immunomarker., Conclusions: PV and NV system functions appear to be reflected in selected clinical symptoms that differentially relate to other clinical features, treatment outcomes, and immunological function., (© 2020 Wiley Periodicals, Inc.)

Importance: Despite the widespread awareness of functional magnetic resonance imaging findings suggesting a role for cortical connectivity networks in treatment selection for major depressive disorder, its clinical utility remains limited. Recent methodological advances have revealed functional magnetic resonance imaging-like connectivity networks using electroencephalography (EEG), a tool more easily implemented in clinical practice., Objective: To determine whether EEG connectivity could reveal neural moderators of antidepressant treatment., Design, Setting, and Participants: In this nonprespecified secondary analysis, data were analyzed from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinic Care study, a placebo-controlled, double-blinded randomized clinical trial. Recruitment began July 29, 2011, and was completed December 15, 2015. A random sample of 221 outpatients with depression aged 18 to 65 years who were not taking medication for depression was recruited and assessed at 4 clinical sites. Analysis was performed on an intent-to-treat basis. Statistical analysis was performed from November 16, 2018, to May 23, 2019., Interventions: Patients received either the selective serotonin reuptake inhibitor sertraline hydrochloride or placebo for 8 weeks., Main Outcomes and Measures: Electroencephalographic orthogonalized power envelope connectivity analyses were applied to resting-state EEG data. Intent-to-treat prediction linear mixed models were used to determine which pretreatment connectivity patterns were associated with response to sertraline vs placebo. The primary clinical outcome was the total score on the 17-item Hamilton Rating Scale for Depression, administered at each study visit., Results: Of the participants recruited, 9 withdrew after first dose owing to reported adverse effects, and 221 participants (150 women; mean [SD] age, 37.8 [12.7] years) underwent EEG recordings and had high-quality pretreatment EEG data. After correction for multiple comparisons, connectome-wide analyses revealed moderation by connections within and between widespread cortical regions-most prominently parietal-for both the antidepressant and placebo groups. Greater alpha-band and lower gamma-band connectivity predicted better placebo outcomes and worse antidepressant outcomes. Lower connectivity levels in these moderating connections were associated with higher levels of anhedonia. Connectivity features that moderate treatment response differentially by treatment group were distinct from connectivity features that change from baseline to 1 week into treatment. The group mean (SD) score on the 17-item Hamilton Rating Scale for Depression was 18.35 (4.58) at baseline and 26.14 (30.37) across all time points., Conclusions and Relevance: These findings establish the utility of EEG-based network functional connectivity analyses for differentiating between responses to an antidepressant vs placebo. A role emerged for parietal cortical regions in predicting placebo outcome. From a treatment perspective, capitalizing on the therapeutic components leading to placebo response differentially from antidepressant response should provide an alternative direction toward establishing a placebo signature in clinical trials, thereby enhancing the signal detection in randomized clinical trials., Trial Registration: ClinicalTrials.gov identifier: NCT01407094.

Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space machine-learning algorithm tailored for resting-state electroencephalography (EEG) and applied it to data from the largest imaging-coupled, placebo-controlled antidepressant study (n = 309). Symptom improvement was robustly predicted in a manner both specific for the antidepressant sertraline (versus placebo) and generalizable across different study sites and EEG equipment. This sertraline-predictive EEG signature generalized to two depression samples, wherein it reflected general antidepressant medication responsivity and related differentially to a repetitive transcranial magnetic stimulation treatment outcome. Furthermore, we found that the sertraline resting-state EEG signature indexed prefrontal neural responsivity, as measured by concurrent transcranial magnetic stimulation and EEG. Our findings advance the neurobiological understanding of antidepressant treatment through an EEG-tailored computational model and provide a clinical avenue for personalized treatment of depression.

Depression has a chronic and recurrent course often with early onset and is the leading cause of disability worldwide. In contrast to diagnoses for other conditions which rely on precise medical tests, the diagnosis of depression still focuses exclusively on symptom reports. As a result, heterogeneous patient groups are included under broad categories. Furthermore, in the absence of companion diagnostic tests, choosing specific treatments for patients remains imprecise with only one-third of patients entering remission with initial treatment, with others requiring multiple intervention steps to achieve remission. In addition to improving treatment outcomes, disease prevention is essential to reduce overall disease burden. Adolescence is a critical window where complex emotional, social, familial, and biological shifts may predispose to lifelong depression. Thus, personalized medicine, integrating individual variability in genes, brain function, and clinical phenotypes, can offer a comprehensive approach to provide precise diagnosis, novel drug development, optimal treatment assignment, and prevention of illness and its associated burden. Texas Resilience Against Depression study (T-RAD) encompasses two natural history, longitudinal (10 + years), prospective studies (D2K and RAD), each enrolling 2500 participants. The D2K study follows participants (ages 10 years and older) who have a current or past diagnosis of depression or bipolar disorder. The RAD study follows participants aged 10-24 years who are at risk for depression but not yet suffering from the disease. The T-RAD study will help to uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to mood disorder onset, recurrence, progression, and differential treatment response., Competing Interests: Declaration of competing interest Dr. Trivedi has received funding from Agency for Healthcare Research and Quality (AHRQ), Cyberonics Inc., National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Johnson & Johnson. He has also served as an advisor or consultant for Abbott Laboratories Inc., Akzo (Organon Pharmaceuticals Inc.), Allergan Sales LLC, Alkermes, Arcadia Pharmaceuticals Inc., AstraZeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb Company, Cephalon Inc., Cerecor, Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals Inc., Forest Pharmaceuticals, GlaxoSmithKline, Global Medical Education Inc., Health Research Associates, Johnson & Johnson, Lundbeck, MedAvante, Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America Inc., MSI Methylation Sciences Inc., Nestle Health Science-PamLab Inc., Naurex, Neuronetics, One Carbon Therapeutics Ltd., Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd., Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. Dr. Jha has received contract research funding from Acadia Pharmaceutical and Janssen Research. Dr. Trombello currently owns stock in Merck and Gilead Sciences. Dr. Hughes has served as Youth Aware of Mental Health (YAM) trainer, consulting for Mental Health in Mind International. Dr. Hughes also receives royalties from Guilford Press. Dr. Greer has received contract research support from Janssen Research and Development, grant funding from NARSAD, and consultant/honoraria for Lundbeck and Takeda. Drs. Chin Fatt, Cooper, Mason, Toll, Gadad, Czysz, Minhajuddin, Fuller, Carmody, Ms. Sethuram, Mrs. Mayes have no disclosures to report., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: This report describes outcomes of an ongoing quality-improvement project (VitalSign6) in a large US metropolitan area to improve recognition, treatment, and outcomes of depressed patients in 16 primary care clinics (6 charity clinics, 6 federally qualified health care centers, 2 private clinics serving low-income populations, and 2 private clinics serving patients with either Medicare or private insurance)., Methods: Inclusion in this retrospective analysis was restricted to the first 25,000 patients (aged ≥12 years) screened with the 2-item Patient Health Questionnaire (PHQ-2) in the aforementioned quality-improvement project. Further evaluations with self-reports and clinician assessments were recorded for those with positive screen (PHQ-2 >2). Data collected from August 2014 though November 2016 were available at 3 levels: (1) initial PHQ-2 (n = 25,000), (2) positive screen (n = 4,325), and (3) clinician-diagnosed depressive disorder with 18 or more weeks of enrollment (n = 2,160)., Results: Overall, 17.3% (4,325/25,000) of patients screened positive for depression. Of positive screens, 56.1% (2,426/4,325) had clinician-diagnosed depressive disorder. Of those enrolled for 18 or more weeks, 64.8% were started on measurement-based pharmacotherapy and 8.9% referred externally. Of the 1,400 patients started on pharmacotherapy, 45.5%, 30.2%, 12.6%, and 11.6% had 0, 1, 2, and 3 or more follow-up visits, respectively. Remission rates were 20.3% (86/423), 31.6% (56/177), and 41.7% (68/163) for those with 1, 2, and 3 or more follow-up visits, respectively. Baseline characteristics associated with higher attrition were: non-white, positive drug-abuse screen, lower depression/anxiety symptom severity, and younger age., Conclusion: Although remission rates are high in those with 3 or more follow-up visits after routine screening and treatment of depression, attrition from care is a significant issue adversely affecting outcomes., (© 2019 Annals of Family Medicine, Inc.)

Major depressive disorder (MDD) and relationship discord between cohabiting partners frequently co-occur, with bidirectional effects established. As relationship quality influences understanding and treatment of MDD, the current analyses clarified the relations of pretreatment dyadic discord with outcomes during and at the end of acute phase cognitive therapy (CT) for adults with recurrent MDD. Married or cohabiting patients (n = 219) completed the Dyadic Adjustment Scale (DYS) before and after a 16-20 session, 12-14 week CT protocol. Lower levels of dyadic adjustment indicated higher levels of dyadic discord. Response to CT was defined as the absence of a major depressive episode and ≤ 12 on the 17-item Hamilton Rating Scale for Depression. Pretreatment dyadic discord, whether defined as a continuous or categorical variable (using DYS cutoff score of 97), was not associated with treatment completion or response but was positively associated with levels of depressive symptoms at the end of acute phase CT. Furthermore, CT was associated with declines in dyadic discord, with 23.3% of initially discordant couples moving to nondiscordant status at the end of CT. Depressive symptoms did not significantly mediate changes in dyadic discord. Finally, pre- (but not mid-) treatment dyadic discord was associated with subsequent changes in depressive symptoms, suggesting limited mediation. These findings replicate prior research indicating that individual CT is associated with reductions in depressive symptoms and dyadic discord while clarifying that lower pre-treatment dyadic discord may predict initial improvement in depressive symptoms., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Baseline rostral anterior cingulate cortex (rACC) activity is a well-replicated nonspecific predictor of depression improvement. The rACC is a key hub of the default mode network, which prior studies indicate is hyperactive in major depressive disorder. Because default mode network downregulation is reliant on input from the salience network and frontoparietal network, an important question is whether rACC connectivity with these systems contributes to depression improvement., Methods: Our study evaluated this hypothesis in outpatients (N = 238; 151 female) enrolled in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) 8-week randomized clinical trial of sertraline versus placebo for major depressive disorder. Depression severity was measured using the Hamilton Rating Scale for Depression, and electroencephalography was recorded at baseline and week 1. Exact low-resolution electromagnetic tomography was used to compute activity from the rACC, and key regions within the default mode network (posterior cingulate cortex), frontoparietal network (left dorsolateral prefrontal cortex), and salience network (right anterior insula [rAI]). Connectivity in the theta band (4.5-7 Hz) and beta band (12.5-21 Hz) was computed using lagged phase synchronization., Results: Stronger baseline theta-band rACC-rAI (salience network hub) connectivity predicted greater depression improvement across 8 weeks of treatment for both treatment arms (B = -0.57, 95% confidence interval = -1.07, -0.08, p = .03). Early increases in theta-band rACC-rAI connectivity predicted greater likelihood of achieving remission at week 8 (odds ratio = 2.90, p = .03)., Conclusions: Among patients undergoing treatment, theta-band rACC-rAI connectivity is a prognostic, albeit treatment-nonspecific, indicator of depression improvement, and early connectivity changes may predict clinically meaningful outcomes., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Major depressive disorder affects one in five adults in the United States. While practice guidelines recommend universal screening for depression in primary care settings, clinical outcomes suffer in the absence of optimal models to manage those who screen positive for depression. The current practice of employing additional mental health professionals perpetuates the assumption that primary care providers (PCP) cannot effectively manage depression, which is not feasible, due to the added costs and shortage of mental health professionals. We have extended our previous work, which demonstrated similar treatment outcomes for depression in primary care and psychiatric settings, using measurement-based care (MBC) by developing a model, called Primary Care First (PCP-First), that empowers PCPs to effectively manage depression in their patients. This model incorporates health information technology tools, through an electronic health records (EHR) integrated web-application and facilitates the following five components: (1) Screening (2) diagnosis (3) treatment selection (4) treatment implementation and (5) treatment revision. We have implemented this model as part of a quality improvement project, called VitalSign 6 , and will measure its success using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework. In this report, we provide the background and rationale of the PCP-First model and the operationalization of VitalSign 6 project.

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.

Although people with depressive symptoms face criticism, hostility, and rejection in their close relationships, we do not know how they respond. Following interpersonal theories of depression, it might be expected that depressive symptoms would be associated with a tendency to receive and also to express criticism toward one's spouse, and that at least some of this criticism would be a contingent response to criticism received (i.e., "counter-criticism"). However, other research has determined that depressive symptoms/behaviors suppress partner criticism, suggesting that depressed people might respond to partner criticism similarly, by subsequently expressing less criticism. In a sample of 112 married couples, partial correlations, regressions, and Actor-Partner Interdependence Modeling indicated that lower criticism and counter-criticism expression during a laboratory marital interaction task was associated with higher depressive symptoms, especially when such individuals were clinically depressed. Furthermore, during a separate and private Five-Minute Speech Sample, lower criticism by partners was associated with higher depressive symptoms, especially when those who chose the interaction topic were also clinically depressed. All analyses controlled for relationship adjustment. These results suggest that spouses with higher depressive symptoms and clinical depression diagnoses may be suppressing otherwise ordinary criticism expression toward their nondepressed partners; furthermore, nondepressed partners of depressed people are especially likely to display less criticism toward their spouse in a private task., (© 2018 Family Process Institute.)

Background/aims: While substantial prior research has evaluated the psychometric properties of the 12-item Concise Health Risk Tracking-Self Report (CHRT-SR 12 ), a measure of suicide propensity and suicidal thoughts, no prior research has investigated its factor structure, sensitivity to change over time, and other psychometric properties in a placebo-controlled trial of antidepressant medication, nor determined whether symptoms change throughout treatment., Methods: Participants in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study ( n=278) provided data to evaluate the factor structure and sensitivity to change over time of the CHRT-SR 12 through eight weeks of a clinical trial in which participants received either placebo or antidepressant medication (sertraline)., Results/outcomes: Factor analysis confirmed two factors: propensity (comprised of first-order factors including pessimism, helplessness, social support, and despair) and suicidal thoughts. Internal consistency (α's ranged from 0.69-0.92) and external validity were both acceptable, with the total score and propensity factor scores significantly correlated with total scores and single-item suicidal-thoughts scores on the self-report Quick Inventory of Depressive Symptoms and the clinician-rated 17-item Hamilton Rating Scale for Depression. Through analyzing CHRT-SR 12 changes over eight treatment weeks, the total score and both the factors decreased regardless of baseline suicidal thoughts. Change in clinician-rated suicidal thoughts was reflected by change in both the total score and propensity factor score., Conclusions/interpretation: These results confirm the reliability, validity, and applicability of the CHRT-SR 12 to a placebo-controlled clinical trial of depressed outpatients receiving antidepressant medication.

To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.

Stimulant use disorders are both common and associated with suicidal ideation and attempts. The psychometric properties of the 12-item Concise Health Risk Tracking Scale Self-Report (CHRT-SR), a measure that was created to assess suicidal thinking and several factors associated with a propensity to act, has been established in persons with mood disorders. This is a secondary analysis to assess the CHRT-SR in 302 stimulant abusing patients that had participated in a clinical trial. A confirmatory factor analysis (CFA) was conducted to assess the factor validity of the 12-item CHRT-SR model with a second-order Propensity factor. The CHRT-SR total score and 2 factor scores (Propensity and Suicidal Thoughts) demonstrated acceptable internal consistency and test-retest reliabilities. These two subscales and the total score were modestly but significantly associated with measures of depression and life satisfaction, demonstrating construct validity. Two additional items assessing Impulsivity were also analyzed, and demonstrated acceptable internal consistency, test-retest reliability, and construct validity. The CHRT-SR appears to be a reliable and valid tool to assess suicidality in persons with stimulant use disorder., (Copyright © 2018. Published by Elsevier Ltd.)

The current study aimed to characterize the multifaceted nature of anxiety in patients with major depression by evaluating distinct anxiety factors. We then related these derived anxiety factors to performance on a Flanker Task of cognitive control, in order to further validate these factors. Data were collected from 195 patients with nonpsychotic chronic or recurrent major depression or dysthymic disorder. At baseline, participants completed self-report measures of anxiety, depression, and other related symptoms (mania, suicidality) and clinicians administered a structured diagnostic interview and the Hamilton Rating Scale for Depression, including anxiety/somatization items. Four discrete factors (State Anxiety, Panic, Neuroticism/Worry, and Restlessness/Agitation) emerged, with high degrees of internal consistency. Discriminant and convergent validity analyses also yielded findings in the expected direction. Furthermore, the neuroticism/worry factor was associated with Flanker Task interference, such that individuals higher on neuroticism/worry responded more incorrectly (yet faster) to incongruent vs. congruent trials whereas individuals higher on the fear/panic factor responded more slowly, with no accuracy effect, to the Flanker Task stimuli. These results parse anxiety into four distinct factors that encompass physiological, psychological, and cognitive components of anxiety. While state anxiety, panic and neuroticism/worry are related to existing measures of anxiety, the Restlessness/Agitation factor appears to be a unique measure of general anxious arousal. Furthermore, two factors were independently validated through the Flanker Task. These results suggest that these anxiety domains have distinct behavioral profiles and could have differential responses to distinct treatments., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The self-report Concise Associated Symptoms Tracking Scale (CAST-SR) was developed to track mania, irritability, anxiety, panic, and insomnia symptoms among depressed outpatients receiving antidepressant medication. Given the overlap between these domains, depression, and stimulant use disorders, we reexamined CAST-SR psychometrics in a novel sample: individuals with stimulant use disorder receiving aerobic exercise or health education interventions., Methods: Using the subsample of stimulant-dependent (following DSM-IV criteria) individuals prescribed antidepressants (N = 124) from the multisite Stimulant Reduction Intervention Using Dosed Exercise (CTN-0037) trial (total sample N = 302), conducted July 2010 to February 2013, we analyzed CAST-SR data collected at the first assessment after participant's discharge from residential treatment. We also evaluated the convergent/discriminant validity of the CAST-SR with several self-report questionnaires., Results: Confirmatory factor analysis revealed a 12-item measure composed of 4 factors: irritability, anxiety, panic, and insomnia. This factor structure loaded only in participants prescribed antidepressant medication, not in those who were not prescribed antidepressants. These results replicate the original CAST-SR factor structure, except for the mania factor, which failed to load. Internal consistency was high (α = 0.92 for total scale and α = 0.78-0.89 for the 4 factors), and convergent validity was established, especially for the insomnia and irritability factors, alongside the total score with depressive symptoms, insomnia, quality of life, suicide risk, and physical health measures., Conclusions: These results demonstrate the factor structure, reliability, and validity of the CAST-SR in a novel population of only individuals with stimulant use disorders receiving both exercise/health education interventions and antidepressant medication., Trial Registration: ClinicalTrials.gov identifier: NCT01141608., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Background: One in three clinical trial patients with major depressive disorder report symptomatic improvement with placebo. Strategies to mitigate the effect of placebo responses have focused on modifying study design with variable success. Identifying and excluding or controlling for individuals with a high likelihood of responding to placebo may improve clinical trial efficiency and avoid unnecessary medication trials., Methods: Participants included those assigned to the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological variables to identify the most robust yet parsimonious features that predicted depression severity at the end of the double-blind 8-week trial. Variables retained in at least 50% of the 100 imputed data sets were used in a Bayesian multiple linear regression model to simultaneously predict the probabilities of response and remission., Results: Lower baseline depression severity, younger age, absence of melancholic features or history of physical abuse, less anxious arousal, less anhedonia, less neuroticism, and higher average theta current density in the rostral anterior cingulate predicted a higher likelihood of improvement with placebo. The Bayesian model predicted remission and response with an actionable degree of accuracy (both AUC > 0.73). An interactive calculator was developed predicting the likelihood of placebo response at the individual level., Conclusion: Easy-to-measure clinical, behavioral, and electrophysiological assessments can be used to identify placebo responders with a high degree of accuracy. Development of this calculator based on these findings can be used to identify potential placebo responders., (© 2018 S. Karger AG, Basel.)

Objective: Research analyzing behavioral activation (BA) teletherapy outcomes is limited. Among low-income real-world primary care patients receiving a brief BA teletherapy program for depression and anxiety, we analyzed descriptive statistics and changes in depression and anxiety scores throughout treatment., Methods: One hundred thirty patients completed an intake assessment from June 2015 to August 2016; outcomes included the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7). Data from 74 low-income, primary care patients completing at least one therapy session were analyzed to characterize the demographics of therapy patients, to describe their depression and anxiety symptoms throughout treatment, and to examine whether patients who completed 4 or more sessions had statistically lower exit scores than those completing fewer than 4., Results: Patients were moderately depressed (PHQ-9 score: mean = 14.46) and anxious (GAD-7 score: mean = 11.91) at intake. Patients were predominantly Latino/Latina (68.9%), Spanish-speaking (54.0%), and female (79.7%). The majority of patients who received at least one therapy session achieved and sustained depression remission. Patients who completed ≥ 4 therapy sessions demonstrated lower final session depression (PHQ-9: mean = 5.13, SD = 4.75) and anxiety (GAD-7: mean = 4.77, SD = 4.21) scores compared to those completing < 4 sessions (PHQ-9: mean = 8.04, SD = 6.20, P = .029; GAD-7: mean = 8.00, SD = 6.02, P = .011)., Conclusions: Primary care patients demonstrated improvements in depressive and anxious symptoms throughout BA-based teletherapy. BA teletherapy is feasible and associated with improved outcomes as an adjunct or alternative intervention for primary care providers and in low-income, charity populations.​., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Social/intimate relationship status and quality are associated with health-promoting behaviors, while living alone or being isolated are adversely associated with physical and mental health outcomes. Limited work has investigated how particular components of one's social environment - usual living arrangements, satisfaction with those arrangements, and global social and family discord - are related to substance use reduction and intervention adherence. We investigated these questions in 270 individuals receiving study intervention for stimulant abuse/dependence through the multi-site Stimulant Reduction Intervention using Dosed Exercise (CTN-0037) trial. Using mixed effects modeling, results indicated that individuals with baseline social discord used stimulants on more days throughout the intervention period than those without social discord (d=0.39). An interaction between gender, usual living arrangements, and satisfaction with those arrangements indicated that women who lived alone and were dissatisfied with that arrangement reported greater days of stimulant use compared to several other groups (d≥1.46). Finally, individuals who reported usually living with a non-partner over the past three years attended a greater percentage of intervention sessions compared to those usually living with a partner (d=0.34). These results identify sample subgroups with adverse stimulant use and intervention adherence outcomes and suggest areas for future inquiry/intervention., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Functional impairments often remain despite symptomatic improvement with antidepressant treatment, supporting the need for novel treatment approaches. The present study examined the extent to which exercise augmentation improved several domains of psychosocial functioning and quality of life (QoL) among depressed participants., Methods: Data were collected from 122 partial responders to antidepressant medication. Participants were randomized to either high- (16 kcal/kg of weight/week [KKW]) or low-dose (4-KKW) exercise. Participants completed a combination of supervised and home-based exercise for 12 weeks. The Short-Form Health Survey, Work and Social Adjustment Scale, Social Adjustment Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and Satisfaction with Life Scale were collected at 6 and 12 weeks. Participants with data for at least one of the two follow-up time points (n = 106) were analyzed using a linear mixed model to assess change from baseline within groups and the difference between groups for each psychosocial outcome measure. All analyses controlled for covariates, including baseline depressive symptomatology., Results: Participants experienced significant improvements in functioning across tested domains, and generally fell within a healthy range of functioning on all measures at Weeks 6 and 12. Although no differences were found between exercise groups, improvements were observed across a variety of psychosocial and QoL domains, even in the low-dose exercise group., Conclusions: These findings support exercise augmentation of antidepressant treatment as a viable intervention for treatment-resistant depression to improve function in addition to symptoms., (© 2016 Wiley Periodicals, Inc.)

Major depressive disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria initiative, we used source localization of scalp-recorded EEG resting data to examine the neural correlates of three emerging endophenotypes of depression: neuroticism, blunted reward learning, and cognitive control deficits. Data were drawn from the ongoing multi-site EMBARC study. We estimated intracranial current density for standard EEG frequency bands in 82 unmedicated adults with MDD, using Low-Resolution Brain Electromagnetic Tomography. Region-of-interest and whole-brain analyses tested associations between resting state EEG current density and endophenotypes of interest. Neuroticism was associated with increased resting gamma (36.5-44 Hz) current density in the ventral (subgenual) anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). In contrast, reduced cognitive control correlated with decreased gamma activity in the left dorsolateral prefrontal cortex (dlPFC), decreased theta (6.5-8 Hz) and alpha2 (10.5-12 Hz) activity in the dorsal ACC, and increased alpha2 activity in the right dlPFC. Finally, blunted reward learning correlated with lower OFC and left dlPFC gamma activity. Computational modeling of trial-by-trial reinforcement learning further indicated that lower OFC gamma activity was linked to reduced reward sensitivity. Three putative endophenotypes of depression were found to have partially dissociable resting intracranial EEG correlates, reflecting different underlying neural dysfunctions. Overall, these findings highlight the need to parse the heterogeneity of MDD by focusing on promising endophenotypes linked to specific pathophysiological abnormalities.

Assortative-mating theories propose that individuals select romantic relationship partners who are similar to them on positive and negative qualities. Furthermore, stress-generation and intergenerational transmission of divorce models argue that one's depression history or family-of-origin relationship problems predict qualities of a marital partner that predispose them to relationship distress. We analyzed data from 172 newlywed couples to examine predictors and mediators of a marital partner's risk index. First, an index of one's own and one's partner risk was created through factor analysis and was comprised of measures that indicate insecurity about oneself. This index was significantly correlated with baseline marital satisfaction and, among men, steps toward divorce at follow-up. Then, structural equation modeling tested direct and indirect pathways predicting partner's risk index, analyzing prior depression history and family-of-origin relational impairment as predictors and one's own risk index as the mediator. Results demonstrated that own risk index reliably predicted partner's risk, while own risk index also mediated the relationship between own family-of-origin relational dysfunction/depression history and partner's risk index. These results support assortative mating theories and suggest that the association between adverse family-of-origin relationships or depression history and the risk profile in one's marital partner is explained by one's own risk profile.

This meta-analysis reviewed 126 published empirical articles over the past 50 years describing associations between marital relationship quality and physical health in more than 72,000 individuals. Health outcomes included clinical endpoints (objective assessments of function, disease severity, and mortality; subjective health assessments) and surrogate endpoints (biological markers that substitute for clinical endpoints, such as blood pressure). Biological mediators included cardiovascular reactivity and hypothalamic-pituitary-adrenal axis activity. Greater marital quality was related to better health, with mean effect sizes from r = .07 to .21, including lower risk of mortality (r = .11) and lower cardiovascular reactivity during marital conflict (r = -.13), but not daily cortisol slopes or cortisol reactivity during conflict. The small effect sizes were similar in magnitude to previously found associations between health behaviors (e.g., diet) and health outcomes. Effect sizes for a small subset of clinical outcomes were susceptible to publication bias. In some studies, effect sizes remained significant after accounting for confounds such as age and socioeconomic status. Studies with a higher proportion of women in the sample demonstrated larger effect sizes, but we found little evidence for gender differences in studies that explicitly tested gender moderation, with the exception of surrogate endpoint studies. Our conclusions are limited by small numbers of studies for specific health outcomes, unexplained heterogeneity, and designs that limit causal inferences. These findings highlight the need to explicitly test affective, health behavior, and biological mechanisms in future research, and focus on moderating factors that may alter the relationship between marital quality and health., ((PsycINFO Database Record (c) 2013 APA, all rights reserved).)

Data from 172 newlywed couples were collected over the first 4 years of marriage to test how behaviors demonstrated during marital interactions moderate associations between depressive symptoms and subsequent life stressors. Depressive symptoms and behaviors coded from problem-solving and social support interactions were analyzed as predictors of nonmarital stressors that were interpersonal and dependent on the participant's actions. Behavioral codes were found to moderate 3 of 16 symptom-to-life event associations for husbands. Husbands' reports of more depressive symptoms predicted greater levels of stress when husbands' positive affect and hard negative affect during problem-solving were relatively infrequent and when wives made frequent displays of positive behaviors during husbands' support topics. These effects remained after controlling for marital satisfaction. For wives, behavioral moderators did not interact with depressive symptoms to predict changes in stress, but marital satisfaction consistently interacted with depressive symptoms to predict future stressors beyond interpersonal behaviors. Specifically, for wives, stress generation was more evident when relationship satisfaction was low than when it was high. Our results, though different for men and women, suggest that relationship functioning can alter associations between depressive symptoms and life stress in the early years of marriage. (PsycINFO Database Record (c) 2011 APA, all rights reserved)., (PsycINFO Database Record (c) 2011 APA, all rights reserved.)