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Charles South,1–3 A John Rush,4,* Thomas J Carmody,1–3 Manish K Jha,1,2 Madhukar H Trivedi1,2,*1Center for Depression Research and Clinical Care, 2Department of Psychiatry, 3Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Department of Psychiatry and Behavioral Sciences, Duke-National University of Singapore, Singapore; Duke Medical School, Durham, NC, USA*These authors contributed equally to this work Objective: The objective of the study was to determine whether a unique analytic approach – as a proof of concept – could identify individual depressed outpatients (using 30 baseline clinical and demographic variables) who are very likely (75% certain) to not benefit (NB) or to remit (R), accepting that without sufficient certainty, no prediction (NP) would be made.Methods: Patients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT) + placebo (n=212) or S-CIT + bupropion-SR (n=206) were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient.Results: The two treatment cells had comparable rates of remission (40%) and no benefit (22%). In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R – 85% correct (169 had NP). For S-CIT + placebo, 13 were predicted NB – 69% correct; 44 were predicted R – 75% correct (155 were NP). Overall, 94/418 (22%) patients were identified with a meaningful degree of certainty (69%–85% correct). Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes.Conclusion: In two separate analyses with two different treatments, this analytic approach – which is also applicable to pretreatment laboratory tests – identified a meaningful proportion (over 20%) of depressed patients for whom a treatment outcome was predicted with sufficient certainty that the clinician can elect to strongly recommend for or choose to avoid a particular treatment. Different persons seem to be remitting or not benefiting with these two different treatments.Keywords: patient selection, depression, elastic net, analytic approach, treatment response

Objective: This study evaluated the concordance between the self-report and the clinician-rated versions of the Inventory of Depressive Symptomatology (IDS-30) and between the two versions of the briefer 16-item Quick Inventory of Depressive Symptomatology (QIDS-16).Methods: Data were gathered for 544 adult outpatients with psychotic (N = 106) or nonpsychotic (N = 438) major depressive disorder at 14 public sector mental health clinics in the Texas Medication Algorithm Project. Data for the QIDS-16 were extracted from the IDS-30. Baseline scores and scores from the final study visit at or before month 12 were analyzed. The clinician-rated and the self-report versions of each scale were compared in their identification of response to treatment and remission.Results: The average baseline IDS-SR-30 total score was 2.2 points higher (indicating greater severity) than the IDS-C-30 score; the average QIDS-SR-16 total score was only .3 points higher than the QIDS-C-16 score. The IDS-SR-30 and the IDS-C-30, as well as the QIDS-C-16 and QIDS-SR-16, agreed substantially in classifying response and remission for patients, regardless of whether the patients had psychotic features. None of a large number of clinical and demographic features accounted for differences between the QIDS-SR-16 and QIDS-C-16 total scores.Conclusions: Either the IDS-30 or the QIDS-16 self-report adequately assesses depressive symptom severity among public-sector outpatients with major depressive disorder. The briefer QIDS-16 may be preferred to save time and cost. [ABSTRACT FROM AUTHOR]

Background. Despite increasing adoption of clinical practice guidelines in psychiatry, there is little measurement of provider implementation of these recommendations, and the resulting impact on clinical outcomes. The current study describes one effort to measure these relationships in a cohort of public sector out-patients with bipolar disorder.Method. Participants were enrolled in the algorithm intervention of the Texas Medication Algorithm Project (TMAP). Study methods and the adherence scoring algorithm have been described elsewhere. The current paper addresses the relationships between patient characteristics, provider experience with the algorithm, provider adherence, and clinical outcomes. Measurement of provider adherence includes evaluation of visit frequency, medication choice and dosing, and response to patient symptoms. An exploratory composite 'adherence by visit' score was developed for these analyses.Results. A total of 1948 visits from 141 subjects were evaluated, and utilized a two-stage declining effects model. Providers with more experience using the algorithm tended to adhere less to treatment recommendations. Few patient factors significantly impacted provider adherence. Increased adherence to algorithm recommendations was associated with larger decreases in overall psychiatric symptoms and depressive symptoms over time, but did not impact either immediate or long-term reductions in manic symptoms.Conclusions. Greater provider adherence to treatment guideline recommendations was associated with greater reductions in depressive symptoms and overall psychiatric symptoms over time. Additional research is needed to refine measurement and to further clarify these relationships. [ABSTRACT FROM AUTHOR]

BACKGROUND: The present study provides additional data on the psychometric properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief 16-item symptom severity rating scale that was derived from the longer form. Both the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and self-report (IDS-SR30; QIDS-SR16) formats. METHOD: The patient samples included 544 out-patients with major depressive disorder (MDD) and 402 out-patients with bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses including sensitivity to change with treatment were conducted. RESULTS: Internal consistencies (Cronbach's alpha) ranged from 0.81 to 0.94 for all four scales (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad mood, involvement, energy, concentration and self-outlook had the highest item-total correlations among patients with MDD and BD across all four scales. QIDS-SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at exit (c = 0.83). QIDS-C16 and IDS-C30 total scores were also highly correlated among patients with MDD (c = 0.82) and patients with BD (c = 0.81). The IDS-SR30, IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change, indicating high concurrent validity for all four scales. High concurrent validity was also documented based on the SF-12 Mental Health Summary score for the population divided in quintiles based on their IDS or QIDS score. CONCLUSION: The QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly acceptable psychometric properties and are treatment sensitive measures of symptom severity in depression. [ABSTRACT FROM AUTHOR]

Objectives. The authors analyzed self-reported questionnaire data from the 1987 National Medical Expenditure Survey (NMES) to determine the smoking patterns of veterans. Methods. Using NMES data, the authors compared veterans versus nonveterans overall, women veterans versus women nonveterans, Vietnam-era veterans versus other veterans, and veterans whose usual source of medical care was the Department of Veterans Affairs (VA) system versus veterans who received care elsewhere. Results. The likelihood of ever having smoked cigarettes was higher for veterans than for nonveterans and for women veterans than for women nonveterans. The prevalence of current smoking was higher for veterans than for nonveterans and higher for those seeking care within the VA system than for other veterans. Conclusions. Given the enormous health care costs associated with smoking, health promotion efforts should be developed to reduce the high rate of smoking among veterans-especially those who are consumers of VA health care. [ABSTRACT FROM AUTHOR]

Multiple intervention strategies have been found effective for increasing physical activity among breast cancer survivors, yet most breast cancer survivors fail to meet physical activity recommendations. Optimization of interventions can facilitate real word implementation to ensure effective and efficient intervention delivery. Using a full-factorial design based on the Multiphase Optimization Strategy, 337 breast cancer survivors were randomized to receive a combination of four intervention components: (1) supervised exercise sessions, (2) facility membership, (3) Active Living Every Day (ALED), and (4) Fitbit. Moderate-to vigorous (MVPA) and light-intensity physical activity (LPA) were measured at baseline, 3 months, and 6 months with a hip-worn Actigraph GT3X+. Normal linear mixed models with separate intercepts for each subject were fit in the SAS 9.4 Mixed procedure. Participants who received supervised exercise sessions engaged in more MVPA, 153.58 min/week vs. 133.0 min/week (F = 3.97, p = 0.048) and LPA, 170.26 min/day versus 160.98 light PA minutes/day (F = 4.67, p = 0.032), compared to participants who did not receive supervised exercise. The effects of the three other intervention components on MVPA were not significant; however, those that received ALED engaged in less LPA (F = 6.6, p = 0.011). Supervised exercise sessions resulted in significant increases in MVPA and LPA in a sample of breast cancer survivors. Of note, these sessions were provided only during the first 6 weeks of the intervention and effects remained significant at 6 months. Results of this trial could inform future implementation efforts to ensure effective and efficient delivery of physical activity programs for breast cancer survivors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Methamphetamine use disorder (MethUD) disproportionately affects men who have sex exclusively with men or with men and women (collectively MSM/W), compared to men who have sex with women (MSW). This study is the first MethUD medication trial to compare treatment effect for these groups, hypothesizing that extended-release injectable naltrexone 380mg every 3 weeks plus oral extended-release bupropion 450mg daily would be less effective for MSM/W than MSW., Methods: Data come from men (N = 246) in a multi-site, double-blind, randomized, placebo-controlled trial with sequential parallel comparison design. In Stage 1 (6-weeks), participants were randomized to active treatment or placebo. In Stage 2 (6-weeks), Stage 1 placebo non-responders were rerandomized. Treatment response was ≥3 methamphetamine-negative urine samples, out of four obtained at the end of Stages 1 and 2. Treatment effect was the active-versus-placebo between-group difference in the weighted average Stages 1 and 2 responses., Results: MSM/W (n = 151) were more likely than MSW (n = 95) to be Hispanic, college-educated, and living with HIV. Adjusting for demographics, among MSM/W, response rates were 13.95 % (active treatment) and 2.78 % (placebo) in Stage 1; 23.26 % (active treatment) and 4.26 % (placebo) in Stage 2. Among MSW, response rates were 7.69 % (active treatment) and 5.80 % (placebo) in Stage 1; 3.57 % (active treatment) and 0 % (placebo) in Stage 2. Treatment effect was significantly larger for MSM/W (h = 0.1479) than MSW (h = 0.0227) (p = 0.04)., Conclusions: Findings suggest efficacy of extended-release naltrexone plus bupropion for MSM/W, a population heavily burdened by MethUD. While a secondary outcome, this intriguing finding merits testing in prospective trials., Competing Interests: Declaration of Competing Interest Drs. Kidd and Smiley reports no financial relationships with commercial interests. Dr. Coffin directs an NIH-funded trial that receives donated tenofovir-emtricitabine from Gilead Sciences. Dr. Carmody has been a consultant for Alkermes. Dr. Levin receives grant support from the NIDA, SAMHSA, US World Meds and research support from Aelis Pharmaceuticals. She also receives medication from Indivior for research. In addition, Dr. Levin served as a nonpaid member of a Scientific Advisory Board for Alkermes, Indivior, Novartis, Teva, and US WorldMeds; receives royalties from APA Publishing; and is a consultant to Major League Baseball. Dr. Nunes has served as an uncompensated consultant to Alkermes, Indivior, and Camurus, and as an investigator on NIH-funded studies that received in-kind medication from Alkermes, Indivior, and Braeburn/Camurus, and in-kind digital therapeutics from Pear Therapeutics and Chess Health. Dr. Shoptaw receives clinical support for his research from Gilead Sciences, Alkermes and Indivior. He also consults with Aelis Pharmaceuticals. Dr. Shoptaw is also the Editor-in-Chief at Drug and Alcohol Dependence, an Elsevier journal., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: The Concise Health Risk Tracking Self-Report (CHRT-SR) assesses the risk of suicidal behavior. We report its psychometric properties in a representative sample of adolescent outpatients., Methods: A sample (n = 657) of adolescents (<18 years of age) in primary or psychiatric care completed the 14-item version of CHRT-SR at both baseline and within 3 months. To identify an optimal brief solution for the scale, we evaluated the factor structure of CHRT-SR using multigroup confirmatory factor analysis, and testing measurement invariance across age and gender. The item response theory and classical test theory characteristics of the optimal solution were evaluated. Concurrent validity (both cross-sectional and as a change measure over time) of the optimal solution was assessed by comparing it to another suicide measure., Results: Confirmatory factor analysis identified the 9-item CHRT-SR (CHRT-SR 9 ) as the optimal solution. Classical test theory and item response theory indicated excellent fit. Concurrent validity analyses revealed that it can measure both improvement/worsening of suicidality over time., Conclusion: The CHRT-SR 9 is a brief self-report with excellent psychometric properties in a sample of adolescents that is sensitive to changes in suicidality over time. Its performance in other populations and ability to predict future suicidal events deserves study., (© 2022 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Background: Depressive symptoms result in considerable burden for breast cancer survivors. Increased physical activity may reduce these burdens but existing evidence from physical activity interventions in equivocal. Furthermore, physical activity intervention strategies may differentially impact depressive symptoms, which should be considered in designing and optimizing behavioral interventions for breast cancer survivors., Methods: The Physical Activity for Cancer Survivors (PACES) trial enrolled 336 participants breast cancer survivors, who were 3 months to 10 years post-treatment, and insufficiently active (< 150 min of moderate-to-vigorous physical activity per week). Participants were randomly assigned to a combination of 4 intervention strategies in a full-factorial design: 1) supervised exercise sessions, 2) facility access, 3) Active Living Every Day, and 4) Fitbit self-monitoring. Depressive symptoms were assessed at baseline, mid-intervention (3 months), and post-intervention (6 months) using the Quick Inventory for Depressive Symptoms. Change in depressive symptoms were analyzed using a linear mixed-effects model., Results: Results from the linear mixed-effects model indicated that depressive symptoms decreased significantly across the entire study sample over the 6-month intervention (F = 4.09, p = 0.044). A significant ALED x time interaction indicated participants who received the ALED intervention experienced greater reductions in depressive symptoms (F = 5.29, p = 0.022). No other intervention strategy significantly impacted depressive symptoms., Conclusions: The ALED intervention consists of strategies (i.e., goal setting, social support) that may have a beneficial impact on depressive symptoms above and beyond the effect of increased physical activity. Our findings highlight the need to consider secondary outcomes when designing and optimizing physical activity interventions., Trial Registration: ClinicalTrials.gov NCT03060941. Posted February 23, 2017., (© 2023. The Author(s).)

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.)

Purpose: To evaluate the psychometric properties of a 9-item Concise Health Risk Tracking Self-Report (or CHRT-SR 9 ) to assess suicidal risk in adult primary care outpatients., Methods: Overall, 369 adults completed the original 14-item version of CHRT-SR at baseline and within 4 months thereafter, from which the CHRT-SR 9 was extracted using multigroup confirmatory factor analysis. Measurement invariance (across age and sex) and classical test theory characteristics of the CHRT-SR 9 were evaluated. Concurrent validity was assessed by comparing CHRT-SR 9 responses to those of the suicide item in the Patient Health Questionnaire (PHQ-9), both cross-sectionally and as a change measure over time., Results: Confirmatory factor analysis identified the CHRT-SR 9 as the optimal solution. Factors included pessimism, helplessness, despair (2 items each) and suicidal thoughts (3 items). Measurement invariance held across sex and age groups, indicating that mean differences among sub-groups were real and not attributable to measurement bias. Classical test theory revealed acceptable item-total correlations overall (0.57-0.79) and internal consistency (Spearman-Brown from 0.76 to 0.90). Concurrent validity analyses revealed that the CHRT-SR 9 can measure both improvement and worsening of suicidality over time. A PHQ-9 response of 0, 1, 2, and 3 on the suicide item corresponded to 7.82 (5.53), 16.80 (4.99), 20.71 (5.36), and 25.95 (7.30) (mean and SD) on CHRT-SR 9 total score, respectively., Conclusion: The CHRT-SR 9 is a brief self-report evaluating suicidality with excellent psychometric properties that is sensitive to change over time., Competing Interests: MT has served as an advisor or consultant for Abbott Laboratories, Abdi Ibrahim, AcademyHealth, ACI Clinical, Akili Interactive, Akzo (Organon Pharmaceuticals), Alkermes, Allergan Pharmaceuticals, Alto Neuroscience, American Psychiatric Association, American Society of Clinical Psychopharmacology, Arcadia Pharmaceuticals, AstraZeneca, Avanir Pharmaceuticals Axon Advisors, Axsome Therapeutics, Biogen MA Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Cephalon, Cerebral Inc., Cerecor, Circular Genomics Inc., CME Institute of Physicians, Compass Pathfinder Limited, Concert Pharmaceuticals, Eli Lilly, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GH Research Limited, GlaxoSmithKline, Janssen Global Services, GreenLight VitalSign6 Inc., Heading Health Inc., Janssen Pharmaceutical Products, Jazz Pharmaceutical, Johnson and Johnson Pharmaceutical Research and Development, Legion Health Inc., Libby, Lundbeck, Meade Johnson, MedAvante, Medscape, Medtronic, Merck Sharp and Dohme Corp., Mind Medicine (MindMed) Inc., Mitsubishi Tanabe Pharma Development America, Naki Health, Ltd., Naurex, Navitor, Neurocrine Biosciences Inc., Neuronetics, Noema Pharma AG, Orexo US Inc., Otsuka American Pharmaceutical Inc., Otsuka Canada Pharmaceutical Inc., Otsuka Pharmaceutical Development and Commercialization Inc., Pamlab, Parke-Davis Pharmaceuticals, Perception Neuroscience Holdings, Pfizer, PgxHealth, Pharmerit International, Phoenix Marketing Solutions, Research USA, Praxis Precision Medicines Inc., Relmada Therapeutics, Inc., Rexahn Pharmaceuticals, Ridge Di-agnostics, Roche Products, SAGE Therapeutics, Sepracor, Shire Development, Sierra, SK Life and Science, Signant Health, Sparian Biosciences Inc., Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, WebMD, and WyethAyerst Laboratories and has received grants or research support from the Agency for Healthcare Research and Quality, American Foundation for Suicide Prevention, Blue Cross Blue Shield of Texas, Cancer Prevention and Research Institute of Texas, Cyberonics, Janssen Research and Development, Johnson and Johnson, NARSAD, the National Institute of Drug Abuse, the National Institute of Mental Health, and Patient-Centered Outcomes Research Institute, and has received editorial compensation from The American Psychiatric Association, Engage Health Media, Healthcare Global Village, and Oxford University Press. He owns stock in Alto Neuroscience Inc., Cerebral Inc., Circular Genomics Inc., GreenLight VitalSign6 Inc., and Legion Health Inc. AR has received consulting fees from Compass Inc., Curbstone Consultant LLC., Emmes Corp., Evecxia Therapeutics, Inc., Holmusk Technologies, Inc., ICON, Johnson and Johnson (Janssen), Liva-Nova, Mind Street Inc., Neurocrine Biosciences Inc., Otsuka-US; speaking fees from Johnson and Johnson (Janssen), and Liva-Nova, and royalties from Wolters Kluwer Health, Guilford Press and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives) and AR is also named co-inventor on two patents: U.S. patent no. 7,795,033: Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon F. J., Laje G., Manji H., AR, Paddock S., Wilson A. S., and U.S. patent no. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon F. J., Laje G., Manji H., AR, Paddock S. TC has served as a consultant for Alkermes, Inc. The remaining 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 © 2023 Nandy, Rush, Carmody, Mayes and Trivedi.)

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.)

Several care models have been developed to improve treatment for depression, all of which provide "enhanced" evidence-based care (EEC). The essential component of these approaches is Measurement-Based Care (MBC). Specifically, Collaborative Care (CC), and Algorithm-guided Treatment (AGT), and Integrated Care (IC) all use varying forms of rigorous MBC assessment, care management, and/or treatment algorithms as key instruments to optimize treatment delivery and outcomes for depression. This meta-analysis systematically examined the effectiveness of EEC versus usual care for depressive disorders based on cluster-randomized studies or randomized controlled trials (RCTs). PubMed, the Cochrane Library, and PsycInfo, EMBASE, up to January 6th, 2020 were searched for this meta-analysis. The electronic search was supplemented by a manual search. Standardized mean difference (SMD), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed. A total of 29 studies with 15,255 participants were analyzed. EEC showed better effectiveness with the pooled RR for response of 1.30 (95%CI: 1.13-1.50, I 2  = 81.9%, P < 0.001, 18 studies), remission of 1.35 (95%CI: 1.11-1.64, I 2  = 85.5%, P < 0.001, 18 studies) and symptom reduction with a pooled SMD of -0.42 (95%CI: -0.61-(-0.23), I 2  = 94.3%, P < 0.001, 19 studies). All-cause discontinuations were similar between EEC and usual care with the pooled RR of 1.08 (95%CI: 0.94-1.23, I 2  = 68.0%, P = 0.303, 27 studies). This meta-analysis supported EEC as an evidence-based framework to improve the treatment outcome of depressive disorders.Review registration: PROSPERO: CRD42020163668., (© 2021. The Author(s).)

Aims: The aim of this study was to examine the impact of vigorous intensity, high dose exercise (DEI) on cannabis use among stimulant users compared to a health education intervention (HEI) using data from the Stimulant Reduction Intervention using Dosed Exercise, National Institute of Drug Abuse National Drug Treatment Clinical Trials Network Protocol Number 0037 (STRIDE)., Methods: Adults (N = 302) enrolled in the STRIDE randomized clinical trial were randomized to either the DEI or the HEI. Interventions included supervised sessions three times a week during the Acute phase (12 weeks) and once a week during the Follow-up phase (6 months). Cannabis use was measured at each assessment via Timeline Follow Back and urine drug screens. Cannabis use was compared between the groups during the Acute and Follow-up phases using both the intent-to-treat sample and a complier average causal effects (CACE) analysis., Findings: Approximately 43% of the sample reported cannabis use at baseline. The difference in cannabis use between the DEI and HEI groups during the Acute phase was not significant. During the Follow-up phase, the days of cannabis use was significantly lower among those in the DEI group (1.20 days) compared to the HEI group (2.15 days; p = 0.04)., Conclusions: For those who adhered to the exercise intervention, vigorous intensity, high dose exercise resulted in less cannabis use. Results suggest that there were no significant short-term differences in cannabis use between the groups. Further study on the long-term impact of exercise as a treatment to reduce cannabis use should be considered., (Copyright © 2019. Published by Elsevier B.V.)

Peripheral inflammation is associated with poor response to antidepressant treatments. However, whether sex differentially affects this association remains unknown. Participants of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) with baseline plasma samples were included in this study (n = 220; male n = 75, female n = 145). Depression severity [Hamilton Rating Scale for Depression 17-item (HAMD-17)] was measured at baseline and weeks- 1, 2, 3, 4, 6, and 8. Plasma c-reactive protein (CRP) was measured with commercially-available ELISA kits at baseline, week-1, and week-8. Sex difference in prediction of baseline-to-week-8 HAMD-17 change by baseline CRP was tested with sex-by-baseline-CRP-by-time interaction in mixed model analysis. Additionally, changes in CRP from baseline-to-week-8 CRP and its association with HAMD-17 changes over that period were also evaluated. Covariates included body mass index, site, smoking status, and age. There was a significant sex difference in association of baseline-to-week-8 HAMD-17 reduction with baseline CRP (p = 0.033). Higher baseline CRP was associated with lower baseline-to-week-8 HAMD-17 reduction in females (p < 0.0001) but not in males (p = 0.632). Additionally, CRP was significantly reduced (p = 0.041, effect size = 0.254) from baseline-to-week-8, but there were no sex differences in this reduction (p = 0.249). Baseline-to-week-8 changes in HAMD-17 and CRP were not significantly associated either overall (p = 0.348) or based on sex (p = 0.370). In a large study of depressed outpatients, we replicated previous findings that elevated baseline CRP levels are associated with worse antidepressant treatment outcomes. However, this effect was limited only to females. These findings emphasize the importance of studying sex differences in biological mechanisms linking inflammation and depression., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The 12-item Concise Health Risk Tracking Self-Report (CHRT-SR 12 ) is a brief, self-report measure that systematically assesses both suicidal thinking and associated thoughts that may indicate the propensity for suicidal acts. It can be used as a tool to both assess risk and guide treatment interventions targeting associated cognitions., Methods: This report used acute treatment data from a clinically representative sample of outpatients with nonpsychotic major depressive disorder (N = 665) participating in the Combining Medications to Enhance Depression Outcomes trial, who received up to 12 weeks of escitalopram, escitalopram plus bupropion SR, or venlafaxine XR plus mirtazapine. Outcome assessors and patients were masked to treatment., Results: Factor analysis of CHRT-SR 12 confirmed that the 12 items have higher order structure with two subscales (Propensity, Suicidal Thoughts) and a total score. Internal consistencies were acceptable for both subscales and total score. All three scales were modestly correlated with overall depression severity (r = 0.54 to r = 0.21) and highly discriminating among patients grouped by suicide item ratings on three different depressive symptom ratings. The three scales also distinguished change over the acute phase treatment for those with different levels of baseline suicidal ideation (measured by 30-item Inventory of Depressive Symptomatology (item 18) and for those with change in suicidal ideation (baseline to last visit)., Conclusions: The CHRT-SR 12 has good to excellent psychometric properties and is sensitive to change in suicidal thinking and propensity toward suicidal behavior in outpatients with major depressive disorder. It allows for the monitoring of thoughts and feelings associated with increased suicidal risk as well as levels of thoughts about suicide., (© 2018 Wiley Periodicals, Inc.)

Background: Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these clinical presentations remain unclear. Neuroticism, impaired cognitive control, and blunted reward learning may be critical processes involved in MDD and may help to explain symptoms of anxiety and anhedonia., Methods: Using baseline data from patients with early-onset MDD (N = 296) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, we conducted a path analysis to model relationships between neuroticism, cognitive control, and reward learning to levels of anxiety and anhedonia., Results: Neuroticism was positively associated with both anhedonia (standardized coefficient = 0.26, p < .001) and anxiety (standardized coefficient = 0.40, p < .001). Cognitive control was negatively associated with anxiety (standardized coefficient = -0.18, p < .05). Reward learning was not significantly associated with either anxiety or anhedonia., Limitations: Extraneous variables not included in the model may have even more influence in explaining symptoms of anxiety and anhedonia. Restricted range in these variables may have attenuated some of the hypothesized relationships. Most important, because this was a cross-sectional analysis in a currently depressed sample, we cannot draw any causal conclusions without experimental and longitudinal data., Conclusions: These cross-sectional findings suggest that neuroticism may contribute to anxiety and anhedonia in patients with early onset and either chronic or recurrent MDD, while enhanced cognitive control may protect against anxiety., (Copyright © 2018. Published by Elsevier B.V.)

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.

Background: Major depressive disorder (MDD) is often comorbid with metabolic diseases such as obesity, cardiovascular disease, and type 2 diabetes. A potential link between these disorders is adiponectin, an adipocyte-derived circulating hormone with insulin-sensitizing, anti-inflammatory, and neuroplasticity effects. Reductions in plasma levels of adiponectin have been reported in both humans with depression and in the chronic-defeat mouse model of depression. However, the predictive value of adiponectin for treatment response to depression has not been determined., Methods: We investigated the potential predictive effect of baseline adiponectin levels in patients who provided plasma and were undergoing one of three pharmacological treatments (escitalopram monotherapy; escitalopram plus bupropion; and venlafaxine plus mirtazapine) in the Combining Medications to Enhance Depression Outcomes clinical trial (n=160). Specifically, we assessed whether adiponectin moderates-that is, differentially predicts-treatment response among the treatment arms. Improvements with treatment were assessed using change in the clinician-rated 30-item Inventory of Depressive Symptomatology (IDS-C) from baseline through week 12. Moderator effects were tested using separate pairwise repeated measures mixed-effects models with a treatment-arm-by-adiponectin interaction., Results: Baseline adiponectin levels moderated treatment outcome between two combination therapies. Specifically, low adiponectin predicted better response to escitalopram plus bupropion compared to venlafaxine plus mirtazapine, whereas high adiponectin predicted better response to venlafaxine plus mirtazapine compared to escitalopram plus bupropion (F=4.84, p =0.03). Adiponectin levels did not correlate with baseline depression severity ( r =-0.03, p =.59)., Conclusions: Antidepressant selection for patients with MDD can be personalized using pre-treatment blood-based biomarkers, such as adiponectin, thereby improving treatment outcomes.

Background: Despite the significant, empirically supported benefits of physical activity, the majority of breast cancer survivors do not meet recommended guidelines for physical activity. A variety of effective strategies to increase physical activity in breast cancer survivors have been identified. However, it is unknown which of these strategies is most effective or how these strategies might be combined to optimize intervention effectiveness., Methods: The proposed trial uses multiphase optimization strategy (MOST) to evaluate four evidence-based intervention strategies for increasing physical activity in breast cancer survivors. We will enroll 500 breast cancer survivors, age 18 and older, who are 3-months to 5 years post-treatment. Using a full-factorial design, participants will be randomized to receive a combination: 1) supervised exercise, 2) facility access, 3) self-monitoring, and 4) group-based active living counseling. The primary outcome, moderate-to-vigorous physical activity (MVPA) will be measured at baseline, 3 months, and 6 months using an Actigraph GT3X+. To evaluate intervention effects, a linear mixed-effects model will be conducted with MVPA as the outcome and with time (3 months and 6 months) as the within-subjects factor and intervention (i.e., supervised exercise, facility access, self-monitoring, and active living counseling) as the between subjects factor, along with all two-way interactions., Discussion: The purpose of the PACES study is to evaluate multiple strategies for increasing physical activity in breast cancer survivors. Results of this study will provide in an optimized intervention for increasing physical activity in breast cancer survivors., Trial Registration: Clinicaltrials.gov Identifier: NCT03060941 . Registered February 23, 2017.

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.)

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.)

Objective: Remission rates are low with first-step or even second-step antidepressant treatments. Furthermore, despite extensive investments from National Institutes of Health and from industry, novel treatments are not yet available in clinical care for depression. Predictors of treatment response very early in the course of treatment can avoid unnecessarily lengthy trials with ineffective treatments and reduce the trial and error process. This article examines the expression of positive affect immediately following an acute exercise session at the end of the first exercise session as a predictor of treatment response in the National Institute of Mental Health-funded TREAD (Treatment with Exercise Augmentation for Depression) study, which was conducted from April 2003 to August 2007., Methods: 122 subjects with DSM-IV-diagnosed major depressive disorder were randomized to public health dose (16 kcal/kg/wk) or low dose (4 kcal/kg/wk) of exercise for 12 weeks. Affect following the first exercise session was assessed using the Positive and Negative Affect Scale (PANAS), and depressive symptoms were assessed weekly using the Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) (primary outcome measure)., Results: The PANAS composite affect score (positive-negative total) predicted change in IDS-C score (P < .05), as well as treatment response (P < .02) and remission (P < .03) for those in the high-dose group but not in the low-dose group., Conclusions: These findings suggest that the composite positive affect following the first exercise session has clinical utility to predict treatment response to exercise in depression and match the "right patient" with the "right" treatment., Trial Registration: ClinicalTrials.gov identifier: NCT00076258., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Unlabelled: Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 300 participants with early onset (≤30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository., Clinical Trial Registration: Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC). Identifier: NCT01407094. URL: http://clinicaltrials.gov/show/NCT01407094., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI)., Methods: 139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract-based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD., Results: There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry., Conclusions: The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts., (© 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.)

Background: Decision-making processes have been posited to affect treatment outcome in addicted patients., Objective: The present multi-site study assessed whether two measures of decision-making predicted relapse and subsequent use in stimulant-dependent patients., Methods: A total of 160 methamphetamine- or cocaine-dependent patients participating in a multi-site clinical trial evaluating a modified 12-step facilitation intervention for stimulant-dependent patients (STAGE-12) were assessed. Decision-making processes of risk and delay (Iowa Gambling Task [IGT]) and response reversal (Wisconsin Card Sorting Task [WCST]) were obtained shortly after treatment admission followed by assessment of stimulant use over the next six months. The relationships of the IGT and WCST (Perseverative Errors) with relapse (yes/no) and days of stimulant use during the 6-month period following post-randomization were evaluated., Results: Performance on the IGT and WCST did not significantly predict relapse status or time to relapse. Unexpectedly, worse performance on the IGT was associated with a fewer number of stimulant use days (p = 0.001). In contrast, worse performance on the WCST (more perseverative errors) was associated with a greater number of stimulant use days (p = 0.0003). The predictive effects of perseverative errors on subsequent use were confined to methamphetamine-dependent and Minority participants., Conclusions: Decision-making processes, as measured in the current study, do not uniformly predict relapse or subsequent use. A decrease in the salience attribution of non-drug reinforcers may explain the positive relationship between IGT performance and post-relapse use. More comprehensive and global measures of impulsiveness may better assess relapse risk and use.

Objective: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use., Method: A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale., Results: In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed., Conclusions: Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit.

Given the role of sleep in the development and treatment of major depressive disorder (MDD), it is becoming increasingly clear that elucidation of the biological mechanisms underlying sleep disturbances in MDD is crucial to improve treatment outcomes. Sleep disturbances are varied and can present as insomnia and/or hypersomnia. Though research has examined the biological underpinnings of insomnia in MDD, little is known about the role of biomarkers in hypersomnia associated with MDD. This paper examines biomarkers associated with changes in hypersomnia and insomnia and as predictors of improvements in sleep quality following exercise augmentation in persons with MDD. Subjects with non-remitted MDD were randomized to augmentation with one of two doses of aerobic exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. The four sleep-related items on the clinician-rated Inventory of Depressive Symptomatology (sleep onset insomnia, mid-nocturnal insomnia, early morning insomnia and hypersomnia) assessed self-reported sleep quality. Inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6) and brain-derived neurotrophic factor (BDNF) were assessed in blood samples collected before and following the 12-week intervention. Reduction in hypersomnia was correlated with reductions in BDNF (ρ = 0.26, P = 0.029) and IL-1β (ρ = 0.37, P = 0.002). Changes in these biomarkers were not associated with changes in insomnia; however, lower baseline levels of IL-1β were predictive of greater improvements in insomnia (F = 3.87, P = 0.050). In conclusion, improvement in hypersomnia is related to reductions in inflammatory markers and BDNF in persons with non-remitted MDD. Distinct biological mechanisms may explain reductions in insomnia.

Anhedonia or inability to experience pleasure not only is a core symptom of major depressive disorder (MDD), but also is identified as an important component of the positive valence system in the NIMH Research Domain Criteria. The Snaith-Hamilton Pleasure Scale (SHAPS) has been developed for the assessment of hedonic experience or positive valence, but has not been well-studied in depressed outpatient populations. The current study examined the reliability and validity of the SHAPS using a sample of adult outpatients with treatment resistant MDD. Data for the current study were obtained from 122 adult outpatients with a diagnosis of MDD and non-response to adequate treatment with an SSRI and who participated in Project TReatment with Exercise Augmentation for Depression (TREAD). A Principal Components Analysis was used to define the dimensionality of the SHAPS. Convergent and discriminant validity were evaluated via correlations of the SHAPS total score with "gold standard" measures of depression severity and quality of life. The SHAPS was found to have high internal consistency (Cronbach's coefficient α = .82). A Principal Components Analysis suggests that the SHAPS is mainly "unidimensional" and limited to hedonic experience among adult outpatients with MDD. Convergent and discriminant validity were assessed by examining the Spearman rank-order correlation coefficient between the SHAPS total score and the HRSD17 (rs = 0.22, p < .03), IDS-C30 (rs = 0.26, p < .01), IDS-SR30 (rs = 0.23, p < .02), QIDS-C16 (rs = 0.22, p < .03), QIDS-SR16 (rs = 0.17, p < .10), QLES-Q (rs = -0.32, p < .002), and the pleasure/enjoyment item (sub-item 21) of the IDS-C (rs = 0.44, p < .0001) and IDS-SR (rs = 0.38, p < .0002). The self-administered SHAPS showed modest sensitivity (76%) and specificity (54%) with the self-administered pleasure/enjoyment single item (sub-item 21) of IDS-SR30. The current study shows that the SHAPS is a reliable and valid instrument to assess hedonic experience or positive valence in adult outpatients with MDD and provides a broader assessment of this important domain., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Although bipolar disorder and substance dependence are both associated with treatment non-adherence and cognitive impairment, no studies have investigated relationships between treatment adherence and cognitive functioning in this population. As part of a clinical trial, baseline performance on two neuropsychological tests in 120 outpatients with bipolar disorder and cocaine dependence was used to examine whether cognitive functioning was associated with appointment attendance, medication adherence, and return of medication bottles. This study found that higher baseline cognitive functioning measured by the Stroop Color-Word condition predicted better treatment adherence. However, this study also reports measurement sensitivity of cognition as it relates to treatment adherence when applied to this dual diagnosis population. Poorer performance in simple visual attention tasks as assessed by the Stroop Word condition was inversely associated with some measures of adherence. Future studies are warranted that include a comprehensive neuropsychological battery and advanced medication adherence measures to confirm these findings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment nonadherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study., Methods: Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/d) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, Penn Alcohol Craving Scale, liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model., Results: Baseline and demographic characteristics in the 2 groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks per day or other alcohol-related or mood measures (p > 0.05). Overall side effect burden, glucose, and cholesterol were similar in the 2 groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. -2.0 lbs [SE 1.4], p = 0.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p = 0.04) with quetiapine (+0.40 [SE 0.3]) than placebo (-0.52 [SE 0.3]) at week 6 but not week 12. Retention (survival) in the study was similar in the groups., Conclusions: Findings suggest that quetiapine does not reduce alcohol consumption in patients with BPD and alcohol dependence., (Copyright © 2014 by the Research Society on Alcoholism.)

Exercise is an efficacious treatment for major depressive disorder (MDD) and has independently been shown to have anti-inflammatory effects in non-depressed subjects. Patients with MDD have elevated inflammatory cytokines but it is not known if exercise affects inflammation in MDD patients and whether these changes are clinically relevant. In the TReatment with Exercise Augmentation for Depression (TREAD) study, participants who were partial responders to a selective serotonin reuptake inhibitor were randomized to receive one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW), or 4 KKW for 12 weeks. Blood samples were collected before initiation and again at the end of the 12-week exercise intervention. Serum was analyzed using a multiplexed ELISA for interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher baseline levels of TNF-α were associated with greater decrease in depression symptoms over the 12-week exercise period (P<0.0001). In addition, a significant positive correlation between change in IL-1β and change in depression symptom scores was observed (P=0.04). There were no significant changes in mean level of any cytokine following the 12-week intervention, and no significant relationship between exercise dose and change in mean cytokine level. Results suggest that high TNF-α may differentially predict better outcomes with exercise treatment as opposed to antidepressant medications for which high TNF-α is linked to poor response. Our results also confirm findings from studies of antidepressant medications that tie decreasing IL-1β to positive depression treatment outcomes.

Background: Corticosteroid excess is associated with declarative memory impairment and hippocampal atrophy. These findings are clinically important because approximately 1% of the population receives prescription corticosteroids at any time, and major depressive disorder is associated with elevated cortisol levels and hippocampal atrophy. In animals, hippocampal changes with corticosteroids are blocked by phenytoin. The objective of the current study was to extend these preclinical findings to humans. We examined whether phenytoin attenuated the effects of hydrocortisone on declarative memory. Functional magnetic resonance imaging (fMRI) assessed task-related hippocampal activation., Methods: A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in 17 healthy adult volunteers. Participants received hydrocortisone (2.5 days), phenytoin (3.5 days), both medications together, or placebo, with 21-day washouts between conditions. Differences between treatments were estimated using a mixed-effects repeated measures analysis., Results: Fifteen participants had data from at least two treatment conditions and were used in the analysis. Basal cortisol levels negatively correlated with fMRI BOLD activation in the para-hippocampus with a similar trend observed in the hippocampus. Decrease in declarative memory with hydrocortisone was blocked with concomitant phenytoin administration. Relative to the placebo condition, a significant decrease in hippocampal BOLD activation was observed with hydrocortisone and phenytoin alone, and the two medications in combination. Declarative memory did not show significant correlations with hippocampal activation., Limitations: The modest sample size, which limited our statistical power, was a limitation., Conclusions: Findings from this pilot study suggest phenytoin attenuated effects of corticosteroids memory in humans, but potentiated the reduction in hippocampal activation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Sleep disturbances are persistent residual symptoms following remission of major depressive disorder (MDD) and are associated with an increased risk of MDD recurrence. The purpose of the current study was to examine the effect of exercise augmentation on self-reported sleep quality in participants with non-remitted MDD. Method Participants were randomized to receive selective serotonin reuptake inhibitor (SSRI) augmentation with one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). The four sleep-related items on the IDS-C (Sleep Onset Insomnia, Mid-Nocturnal Insomnia, Early Morning Insomnia, and Hypersomnia) were used to assess self-reported sleep quality., Results: Significant decreases in total insomnia (p < 0.0001) were observed, along with decreases in sleep onset, mid-nocturnal and early-morning insomnia (p's <0.002). Hypersomnia did not change significantly (p = 0.38). Changes in total, mid-nocturnal and early-morning insomnia were independent of changes in depressive symptoms. Higher baseline hypersomnia predicted a greater decrease in depression severity following exercise treatment (p = 0.0057). No significant moderating effect of any baseline sleep on change in depression severity was observed. There were no significant differences between exercise treatment groups on total insomnia or any individual sleep item., Conclusions: Exercise augmentation resulted in improvements in self-reported sleep quality in patients with non-remitted MDD. Given the prevalence of insomnia as a residual symptom following MDD treatment and the associated risk of MDD recurrence, exercise augmentation may have an important role in the treatment of MDD.

Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1-10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.

This study sought to characterize the psychosis phenotype, contrasting cognitive features within traditional diagnosis and psychosis dimension in a family sample containing both schizophrenia and psychotic bipolar I disorder. Seventy-six probands with psychosis [44 probands with schizophrenia, 32 probands with psychotic bipolar I disorder] and 55 first-degree relatives [30 relatives of schizophrenia probands, 25 relatives of bipolar probands] were recruited. Standardized clinical and neuropsychological measures were administered. No differences in cognitive performance emerged between probands with schizophrenia and probands with psychotic bipolar disorder, or between relatives of probands with schizophrenia and relatives of probands with bipolar disorder in the domains of working and declarative memory, executive function and attention. Relatives overall showed higher cognitive performance compared to probands, as expected. However, when we segmented the probands and relatives along a psychosis dimension, independent of diagnostic groups, results revealed lower cognitive performance in probands compared to relatives without psychosis spectrum disorders, whereas relatives with psychosis spectrum disorders showed an intermediate level of performance across all cognitive domains. In this study, cognitive performance did not distinguish either probands or their first-degree relatives within traditional diagnostic groups (schizophrenia and psychotic bipolar disorder), but distinguished probands and relatives with and without lifetime psychosis manifestations independent of diagnostic categories. These data support the notion that schizophrenia and psychotic bipolar disorder present a clinical continuum with overlapping cognitive features defining the psychosis phenotype., (Published by Elsevier Ireland Ltd.)

Background: Depression is common in asthma and may be a risk factor for asthma-related morbidity and mortality. However, minimal data are available on depression treatment in asthma. Previously, we reported greater sustained depression remission and less oral corticosteroid use in asthma patients treated with citalopram., Method: A 12-week randomized, double-blind, placebo-controlled, proof-of-concept trial of escitalopram was conducted in 26 outpatients with asthma requiring at least one course of oral corticosteroids in the prior 12 months and major depressive disorder (MDD) with baseline Hamilton Rating Scale for Depression (HAM-D) scores of ≥ 20., Results: Total evaluable sample (n = 25) showed significant baseline to exit reduction in HAM-D and Inventory of Depressive Symptomatology-Self Report (IDS-SR) scores, with no significant between-group differences, although the findings favored escitalopram. Depression remission on the HAM-D, from week 1 to exit, showed a trend (P = 0.06) favoring escitalopram. Relative risk for remission at week 12 was 6.5 with an estimated remission rate of 39.1% with escitalopram and 6.0% with placebo. Between-group differences in oral corticosteroid use were not significant. Changes in Asthma Control Questionnaire (ACQ) correlated significantly with changes in IDS-SR in the escitalopram, placebo, and combined sample groups (τ = 0.49-0.60, P < 0.05) and with changes in HAM-D only in placebo and combined groups (τ = 0.38-0.58, P < 0.05)., Conclusions: Medium effect sizes and a remission trend were observed favoring escitalopram over placebo on depression measures. Changes in self-reported depressive symptoms correlated with changes in asthma symptoms. A larger trial is needed to confirm the findings from this pilot study., (Copyright © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Brain Derived Neurotrophic Factor (BDNF) has potential as a biomarker of depression treatment because serum BDNF in depressed human subjects is decreased and normalizes with treatment. The relationship between serum BDNF and exercise treatment of depression is not known. The Treatment with Exercise Augmentation for Depression (TREAD) study examined dosed exercise augmentation treatment of partial responders to antidepressants. Serum BDNF in TREAD subjects was analyzed to understand its relationship with exercise training., Methods: Subjects were randomized to high (16 kcal/kg/week or KKW) or low (4 KKW) energy expenditure exercise over 12 weeks. Actual kcal/week expended and IDS-C scores were collected weekly. One hundred four subjects in TREAD provided baseline blood samples; a subset of 70 subjects also provided week 12 samples. Serum BDNF was determined using ELISA. Correlations were examined between change in BDNF and 1) mean kcal/week expended, and 2) change in IDS-C score. Mixed-effects ANOVA examined the effect of baseline BDNF on outcome., Results: Resting serum BDNF was stable and did not correlate with energy expenditure (p = 0.15) or IDS-C improvement (p = 0.89). Subjects entering the study with higher BDNF improved more rapidly on the IDS-C (p = 0.003)., Limitations: Serum may not be the most sensitive blood fraction in which to measure BDNF change. Pre-treatment with medication may mask exercise effect on BDNF., Conclusions: These results suggest that change in serum BDNF does not reflect efficacy of exercise augmentation treatment of MDD. Instead BDNF may function as an augmentation moderator. Pre-treatments that raise BDNF may improve the efficacy of exercise treatment of MDD., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Most patients with major depressive disorder (MDD) require second-step treatments to achieve remission. The Treatment with Exercise Augmentation for Depression (TREAD) study was designed to test the efficacy of aerobic exercise as an augmentation treatment for MDD patients who had not remitted with antidepressant treatment., Method: Eligible participants in this randomized controlled trial were sedentary individuals (men and women aged 18-70 years) diagnosed with DSM-IV nonpsychotic MDD who had not remitted with selective serotonin reuptake inhibitor (SSRI) treatment. Participants were recruited through physician referrals and advertisements. A total of 126 participants were randomized to augmentation treatment with either 16 kcal per kg per week (KKW) or 4 KKW of exercise expenditure for 12 weeks while SSRI treatment was held constant. Supervised sessions were conducted at The Cooper Institute, Dallas, Texas, with additional home-based sessions as needed to fulfill the weekly exercise prescription. The primary outcome was remission (as determined by a score ≤ 12 on the Inventory of Depressive Symptomatology, Clinician-Rated). The study took place between August 2003 and August 2007., Results: There were significant improvements over time for both groups combined (F₁,₁₂₁ = 39.9, P < .0001), without differential group effect (group effect: F₁,₁₃₄ = 3.2, P = .07; group-by-time effect: F₁,₁₁₉ = 3.8, P = .06). Adjusted remission rates at week 12 were 28.3% versus 15.5% for the 16-KKW and 4-KKW groups, respectively, leading to a number needed to treat (NNT) of 7.8 for 16 KKW versus 4 KKW. Men, regardless of family history of mental illness, and women without a family history of mental illness had higher remission rates by week 12 with higher-dose (women, 39.0%; men, 85.4%) than with lower-dose exercise (women, 5.6%; men, 0.1%) (women: t₉₅ = 2.1, P = .04; men: t₈₈ = 5.4, P < .0001) (NNT: women, 3.0; men, 1.2)., Conclusions: There was a trend for higher remission rates in the higher-dose exercise group (P < .06), with a clinically meaningful NNT of 7.8 in favor of the high exercise dose. Significant differences between groups were found when the moderating effects of gender and family history of mental illness were taken into account and suggest that higher-dose exercise may be better for all men and for women without a family history of mental illness., Trial Registration: clinicaltrials.gov Identifier: NCT00076258., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

The inability to experience pleasure, anhedonia, is recognized as a hallmark symptom of depression. An instrument developed for the assessment of hedonic capacity is the 14-item, self-report, Snaith-Hamilton Pleasure Scale (SHAPS), but its psychometric properties have not been adequately evaluated. This study examined the reliability and validity of the SHAPS using a large sample of adult outpatients with major depressive disorder (MDD). Data for this study were obtained from 461 adult outpatients with a diagnosis of MDD who participated in Implementation of Algorithms using Computerized Treatment Systems Project. Internal consistency of the SHAPS was assessed using the Cronbach's coefficient α. A principal factor analysis was used to define the dimensionality of the SHAPS. Convergent and discriminant validity was assessed by evaluating the Pearson correlations between the SHAPS total score and the pleasure/enjoyment item of the 30-item Inventory of Depressive Symptomatology - Clinician-rating (IDS-C30); Quality of Life, Enjoyment, and Satisfaction Questionnaire; 17-item Hamilton Rating Scale for Depression; IDS-C30; 16-item Quick Inventory of Depressive Symptomatology; and 10-item clinician-rated Montgomery-Asberg Depression Rating Scale, respectively. The internal consistency of the SHAPS was 0.91. A one-factor solution emerged for the SHAPS (eigen-values of the first two initial factors were 5.95 and 0.43, respectively). Pearson correlations revealed a positive linear relationship between the SHAPS total score and the total scores on the 17-item Hamilton Rating Scale for Depression (r=0.49, P<0.0001), IDS-C30 (r=0.56, P<0.0001), 16-item Quick Inventory of Depressive Symptomatology (r=0.55, P<0.0001), and 10-item clinician-rated Montgomery-Asberg Depression Rating Scale (r=0.53, P<0.0001). The SHAPS total score was negatively correlated with the Quality of Life, Enjoyment, and Satisfaction Questionnaire (r=-0.65, P<0.0001). This study shows that the SHAPS is a reliable, valid, and unidimensional instrument used to assess the hedonic capacity in adult outpatients with MDD.

Objective: To evaluate psychometric properties and comparability ability of the Montgomery-Asberg Depression Rating Scale (MADRS) vs. the Quick Inventory of Depressive Symptomatology-Clinician-rated (QIDS-C(16)) and Self-report (QIDS-SR(16)) scales to detect a current major depressive episode in the elderly., Method: Community and clinic subjects (age >or=60 years) were administered the Mini-International Neuropsychiatric Interview (MINI) for DSM-IV and three depression scales randomly. Statistics included classical test and Samejima item response theories, factor analyzes, and receiver operating characteristic methods., Results: In 229 elderly patients (mean age = 73 years, 39% male, 54% current depression), all three scales were unidimensional and with nearly equal Cronbach alpha reliability (0.85-0.89). Each scale discriminated persons with major depression from the non-depressed, but the QIDS-C(16) was slightly more accurate., Conclusion: All three tests are valid for detecting geriatric major depression with the QIDS-C(16) being slightly better. Self-rated QIDS-SR(16) is recommended as a screening tool as it is least expensive and least time consuming.

Mood and substance-use disorders are both associated with cognitive deficits. Patients with mood and substance-use disorders have poorer cognition than patients with only a mood disorder. Pregnenolone may have beneficial effects on mood and cognition. In a proof-of-concept investigation, 70 participants with bipolar disorder or recurrent major depressive disorder and history of substance abuse/dependence (abstinent for > or =14days prior to enrollment) were randomly assigned to receive pregnenolone (titrated to 100mg/day) or placebo for 8weeks. Participants were assessed using the Mini International Neuropsychiatric Interview, Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT-B), and Stroop Test. Mood was assessed bi-weekly, while cognition was evaluated at baseline, and weeks 4 and 8. Groups were compared using a random regression analysis that used all of the available data. The pregnenolone group showed trends toward greater improvement, relative to placebo, on the HRSD and YMRS. A post hoc analysis of completers found a statistically significant reduction in HRSD scores with pregnenolone as compared to placebo. Pregnenolone appeared to be safe and well tolerated. Findings suggest that pregnenolone use may be associated with some improvement in manic and depressive symptoms, but not cognition in depressed patients with a history of substance use. Larger trials examining the impact of pregnenolone on mood in more narrowly defined populations may be warranted., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Attitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available., Method: The Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated., Results: Evaluation of the ABC's internal consistency yielded Cronbach's alpha of 0.90-0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for all patients and for patients with each disorder. For patients with MDD, lower anticipated benefits of treatment was associated with less symptom improvement and lower odds of treatment response [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.87, p=0.0011]. There was no association between ABC and symptom improvement or treatment response for patients with bipolar disorder or schizophrenia, possibly because these patients had modest benefits with treatment., Conclusions: The ABC is the first self-report that measures patient expectations about the benefits of treatment on everyday functioning, filling an important gap in available assessments of attitudes and expectations about treatment. The ABC is simple, easy to use, and has acceptable psychometric properties for use in research or clinical settings.

Background: Dyadic discord, while common in depression, has not been specifically evaluated as an outcome predictor in chronic major depressive disorder. This study investigated pretreatment dyadic discord as a predictor of non-remission and its relationship to depressive symptom change during acute treatment for chronic depression., Method: Out-patients with chronic depression were randomized to 12 weeks of treatment with nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy or their combination. Measures included the Marital Adjustment Scale (MAS) and the Inventory of Depressive Symptomatology - Self Report (IDS-SR30). Of 681 original patients, 316 were partnered and 171 of these completed a baseline and exit MAS, and at least one post-baseline IDS-SR30. MAS scores were analysed as continuous and categorical variables ('dyadic discord' v. 'no dyadic discord' defined as an MAS score >2.36. Remission was defined as an IDS-SR30 of 14 at exit (equivalent to a 17-item Hamilton Rating Scale for Depression of 7)., Results: Patients with dyadic discord at baseline had lower remission rates (34.1%) than those without dyadic discord (61.2%) (all three treatment groups) (chi2=12.6, df=1, p=0.0004). MAS scores improved significantly with each of the treatments, although the change was reduced by controlling for improvement in depression. Depression remission at exit was associated with less dyadic discord at exit than non-remission for all three groups [for total sample, 1.8 v. 2.4, t(169)=7.3, p<0.0001]., Conclusions: Dyadic discord in chronically depressed patients is predictive of a lower likelihood of remission of depression. Couple therapy for those with dyadic discord may increase remission rates.

Background: Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence., Methods: Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed., Results: The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence., Conclusions: Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.

The clinician-rated, 16-item Quick Inventory of Depressive Symptomatology (QIDS-C16) has been extensively evaluated in patients with major depressive disorder (MDD). This report assesses the psychometric properties of the QIDS-C16 in outpatients with bipolar disorder (BD, N = 405) and MDD (N = 547) and in bipolar patients in the depressed phase only (BD-D) (N = 99) enrolled in the Texas Medication Algorithm Project (TMAP) using classical test theory (CTT) and the Samejima graded item response theory (IRT) model. Values of coefficient alpha were very similar in BD, MDD, and BD-D groups at baseline (alpha = 0.80-0.81) and at exit (alpha = 0.82-0.85). The QIDS-C16 was unidimensional for all three groups. MDD and BD-D patients (n = 99) had comparable symptom levels. The BD-D patients (n = 99) had the most, and bipolar patients in the manic phase had the least depressive symptoms at baseline. IRT analyses indicated that the QIDS-C16 was most sensitive to the measurement of depression for both MDD patients and for BD-D patients in the average range. The QIDS-C16 is suitable for use with patients with BD and can be used as an outcome measure in trials enrolling both BD and MDD patients., (John Wiley & Sons, Ltd)