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Background Rhythms And You (RAY) is an online intervention for bipolar disorders (BD) based on Interpersonal and Social Rhythm Therapy. We examined RAY's feasibility and acceptability for individuals with BD recruited from primary care. Because online interventions may be more effective when paired with human support, we evaluated RAY with and without weekly brief (∼5 min) calls from clinical helpers (CH). Methods Participants (n = 47) meeting criteria for BD I, II or other specified BD, presenting for primary care, were randomly assigned to RAY, RAY-CH, or Adjunctive Reading Material (ARM) control. RAY consisted of 12 weekly online modules. ARM consisted of 12 weekly emails. Participants were assessed at baseline, 4, 8, and 12 weeks. Results RAY showed high completion rates and Client Satisfaction Questionnaire scores (36/47, 77% and 25.1 ± 5.5, respectively; no group differences). Effect sizes for RAY- CH ranged from small [Internal State Scale-Activation Subscale (ISS-ACT); d = 0.3] to large [SF-12 Mental Health Composite Score (SF-12 MHC); d = 1.3]. ARM also showed moderate effects (ISS-ACT d = 0.7; Quick Inventory of Depressive Symptoms, d = 0.8). SF-12 MHC scores showed a time*group interaction (F = 2.38, df = 6,32, p = 0.05) favoring RAY-CH. Number of logins trended toward significant association with improved social rhythm regularity (F = 4.09, df = 1, 17, p = 0.06). Limitations Sample size is small, limiting conclusions that can be drawn. Conclusions Remote delivery of RAY for individuals with BD is feasible and acceptable. More time spent engaged in RAY was associated with greater improvement in social rhythm regularity. Preliminary evidence suggests adding brief human support to RAY may yield better outcomes.

We thank Kaufman et al.1 for their comprehensive review of the many commendable features of the Kiddie-Computerized Adaptive Test (K-CAT). We do wish to clarify what may be a misunderstanding of the intent of the K-CAT and our view of its role in treatment planning.

Objective: Up to 60% of patients with bipolar disorder develop a substance use disorder during their lifetime. The purpose of this paper was to assess the impact of substance use disorders on depression recovery among bipolar patients randomly assigned to different psychotropic medications and psychosocial interventions. We hypothesized that patients with a comorbid substance use disorder would benefit less from psychotherapy regardless of treatment intensity/length compared to patients without a comorbid substance use disorder. Method: We conducted post hoc analyses among bipolar disorder patients ( n = 270) with and without comorbid substance use disorders enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder randomized psychosocial intervention trial. All patients entered during or shortly after the onset of a bipolar depressive episode. Logistic regression and Cox proportional hazard models were used to assess whether current or past substance use disorders moderated the response of patients to intensive psychosocial intervention or brief psychoeducation with collaborative care, operationalized as full recovery from an episode of bipolar depression. Results: Current comorbid substance use disorders significantly predicted likelihood of recovery (odds ratio = 2.25, p = 0.025) and time to recovery (odds ratio = 1.71, p = 0.006) from bipolar depression. We found that 74.5% of patients with a current substance use disorder, compared to 56.5% without a current substance use disorder, recovered from bipolar depression. Past substance use disorders did not predict likelihood of recovery or time to recovery. Current substance use disorders did not significantly moderate response to intensive psychotherapy versus collaborative care. Conclusion: Contrary to our hypotheses, bipolar disorder participants with a current comorbid substance use disorder were more likely to recover from psychosocial treatment for bipolar depression than patients without a current comorbid substance use disorder. If this finding is replicated, it has implications for the ordering of treatment for patients with comorbid bipolar disorder and substance use disorders.

Purpose of review Depression is a complex and burdensome condition; it often leads to personal, societal and economic costs. Despite advances in treatments, its management over time remains a challenge; many treated for depression do not achieve full recovery or remain well for long. Novel ways to monitor patients are warranted, as well as better understanding of contributors to relapse or sustained wellness. Mobile health technologies (m-Health) are emerging as useful tools for real-time assessments of moods, behaviours and activities in a more convenient and less burdensome manner. Yet, there are numerous questions around privacy, reliability and accuracy of data collected via mobile apps. This review provides a critical overview of advances in m-Health and evaluate the future potential of smartphone technology in the assessment and treatment of depression. Recent findings There is an abundance of apps in the market that claim to exert beneficial effects on the management of depression; to date, only a small fraction has been validated in clinical trials or has had the support of academic centers. Summary Although promising, the use of mobile health applications in depression warrants further investigation and incorporation into mainstream research to facilitate greater adoption and validation of its clinical utility.

Key Points Question Can rapid psychometrically sound adaptive diagnostic screening and dimensional severity measures be developed for posttraumatic stress disorder? Findings In this diagnostic study including 713 US military veterans, the Computerized Adaptive Diagnostic–Posttraumatic Stress Disorder measure was shown to have excellent diagnostic accuracy. The Computerized Adaptive Test–Posttraumatic Stress Disorder also provided valid severity ratings and demonstrated convergent validity with the Post-Traumatic Stress Disorder checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Meaning In this study, the Computerized Adaptive Diagnostic–Posttraumatic Stress Disorder and Computerized Adaptive Test–Posttraumatic Stress Disorder measures appeared to provide valid screening diagnoses and severity scores, with substantial reductions in patient and clinician burden., Importance Veterans from recent and past conflicts have high rates of posttraumatic stress disorder (PTSD). Adaptive testing strategies can increase accuracy of diagnostic screening and symptom severity measurement while decreasing patient and clinician burden. Objective To develop and validate a computerized adaptive diagnostic (CAD) screener and computerized adaptive test (CAT) for PTSD symptom severity. Design, Setting, and Participants A diagnostic study of measure development and validation was conducted at a Veterans Health Administration facility. A total of 713 US military veterans were included. The study was conducted from April 25, 2017, to November 10, 2019. Main Outcomes and Measures The participants completed a PTSD-symptom questionnaire from the item bank and provided responses on the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5). A subsample of 304 participants were interviewed using the Clinician-Administered Scale for PTSD for DSM-5. Results Of the 713 participants, 585 were men; mean (SD) age was 52.8 (15.0) years. The CAD-PTSD reproduced the Clinician-Administered Scale for PTSD for DSM-5 PTSD diagnosis with high sensitivity and specificity as evidenced by an area under the curve of 0.91 (95% CI, 0.87-0.95). The CAT-PTSD demonstrated convergent validity with the PCL-5 (r = 0.88) and also tracked PTSD diagnosis (area under the curve = 0.85; 95% CI, 0.79-0.89). The CAT-PTSD reproduced the final 203-item bank score with a correlation of r = 0.95 with a mean of only 10 adaptively administered items, a 95% reduction in patient burden. Conclusions and Relevance Using a maximum of only 6 items, the CAD-PTSD developed in this study was shown to have excellent diagnostic screening accuracy. Similarly, using a mean of 10 items, the CAT-PTSD provided valid severity ratings with excellent convergent validity with an extant scale containing twice the number of items. The 10-item CAT-PTSD also outperformed the 20-item PCL-5 in terms of diagnostic accuracy. The results suggest that scalable, valid, and rapid PTSD diagnostic screening and severity measurement are possible., This diagnostic study develops and validates a tool for use in diagnostic screening of US military veterans for posttraumatic stress disorder.

There are substantial gaps in understanding near-term precursors of suicidal ideation in bipolar II disorder. We evaluated whether repeated patient-reported mood and energy ratings predicted subsequent near-term increases in suicide ideation.Secondary data were used from 86 depressed adults with bipolar II disorder enrolled in one of 3 clinical trials evaluating Interpersonal and Social Rhythm Therapy and/or pharmacotherapy as treatments for depression. Twenty weeks of daily mood and energy ratings and weekly Hamilton Depression Rating Scale (HDRS) were obtained. Penalized regression was used to model trajectories of daily mood and energy ratings in the 3 week window prior to HDRS Suicide Item ratings.Participants completed an average of 68.6 (sd=52) days of mood and energy ratings. Aggregated across the sample, 22% of the 1675 HDRS Suicide Item ratings were non-zero, indicating presence of at least some suicidal thoughts. A cross-validated model with longitudinal ratings of energy and depressed mood within the three weeks prior to HDRS ratings resulted in an AUC of 0.91 for HDRS Suicide item2, accounting for twice the variation when compared to baseline HDRS ratings. Energy, both at low and high levels, was an earlier predictor than mood.Data derived from a heterogeneous treated sample may not generalize to naturalistic samples. Identified suicidal behavior was absent from the sample so it could not be predicted.Prediction models coupled with intensively gathered longitudinal data may shed light on the dynamic course of near-term risk factors for suicidal ideation in bipolar II disorder.

Aims To systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)-bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI-BP)-and propose treatment recommendations based on a synthesis of the evidence. Methods PRISMA-based systematic review of the literature. Results The acute antidepressant (AD) efficacy of LT was supported by several open-label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti-manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant activity, conflicting evidence of both antimanic and maintenance efficacy, and support from two case series of improved sleep in both acute and euthymic states. IPSRT monotherapy for bipolar II depression had acute response rates of 41%, 67%, and 67.4% in two open studies and one RCT, respectively; as adjunctive therapy for bipolar depression in one RCT, and efficacy in reducing relapse in two RCTs. Among euthymic BD subjects with insomnia, a single RCT found CBTI-BP effective in delaying manic relapse and improving sleep. Chronotherapies were generally safe and well-tolerated. Conclusions The outcome literature on the adjunctive use of chronotherapeutic treatments for BP is variable, with evidence bases that differ in size, study quality, level of evidence, and non-standardized treatment protocols. Evidence-informed practice recommendations are offered.

A symposium held at the 31st European College of Neuropsychopharmacology congress in October 2018 in Barcelona, Spain discussed patients' expectations of treatment of their depression and how these can be integrated into patient management. Since treatment non-compliance is a major problem in patients suffering from depression, it is important to identify patients' expectations to improve treatment compliance and in turn efficacy. Currently, there is no established protocol for choosing the right antidepressant therapy, and physicians need to tailor the choice based on the type of depression, its predominant symptoms, medical and psychiatric history of patients, and their previous response to, and adverse events with, treatment. Treatment strategies also need to be adapted to each patient's personality/persona and their personal beliefs, and patients need to be aware of the potential for drug-associated adverse events such as emotional blunting, sexual dysfunction and loss of functional outcomes, as the expectation of these events may limit their impact on treatment discontinuation. Also, placebo effects remain frequent with treatment, and there is currently no agreed method for predicting response to therapy. Of the available methods to determine treatment response, pharmacogenetic testing has limited value while functional imaging may be valuable, but is not practical in routine clinical practice. Online cognitive behavioural therapy (CBT) represents a new option in the clinical management of patients with depression, particularly for patients who may not be able to access direct interaction with a psychotherapist because of the severity of their condition, their geographic location or socioeconomic situation. Online CBT can act as an adjunct to drug treatment and face-to-face psychotherapy, rather than as the sole form of treatment to aid in identifying a patient's needs, thus meeting the treatment gap and improving compliance and efficacy.Funding: Servier. ispartof: ADVANCES IN THERAPY vol:36 issue:SUPPL 3 pages:S73-S90 ispartof: location:United States status: published

We aim to close a methodological gap in analyzing durations of successive events that are subject to induced dependent censoring as well as competing-risk censoring. In the Bipolar Disorder Center for Pennsylvanians study, some patients who managed to recover from their symptomatic entry later developed a new depressive or manic episode. It is of great clinical interest to quantify the association between time to recovery and time to recurrence in patients with bipolar disorder. The estimation of the bivariate distribution of the gap times with independent censoring has been well studied. However, the existing methods cannot be applied to failure times that are censored by competing causes such as in the Bipolar Disorder Center for Pennsylvanians study. Bivariate cumulative incidence function has been used to describe the joint distribution of parallel event times that involve multiple causes. To the best of our knowledge, however, there is no method available for successive events with competing-risk censoring. Therefore, we extend the bivariate cumulative incidence function to successive events data, and propose non-parametric estimators of the bivariate cumulative incidence function and the related conditional cumulative incidence function. Moreover, an odds ratio measure is proposed to describe the cause-specific dependence, leading to the development of a formal test for independence of successive events. Simulation studies demonstrate that the estimators and tests perform well for realistic sample sizes, and our methods can be readily applied to the Bipolar Disorder Center for Pennsylvanians study.

In this Seminar we discuss developments from the past 5 years in the diagnosis, neurobiology, and treatment of major depressive disorder. For diagnosis, psychiatric and medical comorbidity have been emphasised as important factors in improving the appropriate assessment and management of depression. Advances in neurobiology have also increased, and we aim to indicate genetic, molecular, and neuroimaging studies that are relevant for assessment and treatment selection of this disorder. Further studies of depression-specific psychotherapies, the continued application of antidepressants, the development of new treatment compounds, and the status of new somatic treatments are also discussed. We address two treatment-related issues: suicide risk with selective serotonin reuptake inhibitors, and the safety of antidepressants in pregnancy. Although clear advances have been made, no fully satisfactory treatments for major depression are available.(Reprinted with permission from the Lancet 2012; 379: 1045–55)

Objective To understand self-monitoring strategies used independently of clinical treatment by individuals with bipolar disorder (BD), in order to recommend technology design principles to support mental health management.Materials and Methods Participants with BD (N = 552) were recruited through the Depression and Bipolar Support Alliance, the International Bipolar Foundation, and WeSearchTogether.org to complete a survey of closed- and open-ended questions. In this study, we focus on descriptive results and qualitative analyses.Results Individuals reported primarily self-monitoring items related to their bipolar disorder (mood, sleep, finances, exercise, and social interactions), with an increasing trend towards the use of digital tracking methods observed. Most participants reported having positive experiences with technology-based tracking because it enables self-reflection and agency regarding health management and also enhances lines of communication with treatment teams. Reported challenges stem from poor usability or difficulty interpreting self-tracked data.Discussion Two major implications for technology-based self-monitoring emerged from our results. First, technologies can be designed to be more condition-oriented, intuitive, and proactive. Second, more automated forms of digital symptom tracking and intervention are desired, and our results suggest the feasibility of detecting and predicting emotional states from patterns of technology usage. However, we also uncovered tension points, namely that technology designed to support mental health can also be a disruptor.Conclusion This study provides increased understanding of self-monitoring practices, attitudes, and needs of individuals with bipolar disorder. This knowledge bears implications for clinical researchers and practitioners seeking insight into how individuals independently self-manage their condition as well as for researchers designing monitoring technologies to support mental health management.

Objective Bipolar II disorder (BP-II) is associated with marked morbidity and mortality. Quetiapine, the treatment with greatest evidence for efficacy in BP-II depression, is associated with metabolic burden. Psychotherapy, a treatment with few side effects, has not been systematically evaluated in BP-II. This study compared psychotherapy plus placebo to psychotherapy plus pharmacotherapy as treatments for BP-II depression. Methods From 2010 to 2015, unmedicated adults (n = 92) with DSM-IV-TR BP-II depression were randomly assigned to weekly sessions of Interpersonal and Social Rhythm Therapy (IPSRT) plus placebo or IPSRT plus quetiapine and followed for 20 weeks. Results For primary outcomes, IPSRT + quetiapine yielded significantly faster improvement on 17-item Hamilton Depression Rating Scale (F₁,₁₁₅.₄ = 3.924, P = .048) and greater improvement on Young Mania Rating Scale (F₅₈.₅ = 4.242, P = .044) scores. Both groups, however, improved significantly over time with comparable response rates (≥ 50% reduction in depression scores): 67.4% (62/92) in the entire sample, with no between-group differences. Those randomly assigned to their preferred treatment were 4.5 times more likely to respond (OR = 4.48, 95% CI = 1.20-16.77, P = .026). IPSRT + quetiapine assignment was associated with significantly higher body mass index over time (F₆₇.₉₆ = 6.671, P = .012) and rates of dry mouth (79% v. 58%; χ² = 4.0, P = .046) and a trend toward more complaints of oversedation (100% vs 92%; χ² = 3.4, P = .063). Conclusions IPSRT plus quetiapine resulted in greater symptomatic improvement but also more side effects than IPSRT alone. A subset of participants improved with IPSRT alone, although absence of an inactive comparator limits interpretation of this finding. Receipt of preferred treatment was associated with better outcomes. Harms, benefits, and preferences should be considered when recommending treatments for BP-II depression. Trial registration ClinicalTrials.gov identifier: NCT01133821.

Childhood trauma has been related to adverse behavioral, mental, and health outcomes later in life. Sleep may be a potential mechanism through which childhood trauma is related to adverse health. The current retrospective study aimed to characterize the relationship between childhood trauma exposure and sleep health, a novel multidimensional measure of sleep.Participants (N = 161; mean [standard deviation] age = 59.85 [9.06] years; 67.7% female) retrospectively reported trauma exposure using the Trauma History Questionnaire. Childhood trauma was defined as the number of reported traumatic events before 18 years of age. Trauma exposure after 18 years of age and across the life-span was also recorded. Sleep health was derived both from diary- and actigraphy-assessed measures of sleep regularity, timing, efficiency, and duration, subjective sleep satisfaction, and daytime sleepiness from the Epworth Sleepiness Scale. The relationships between childhood trauma exposure and sleep health were examined using hierarchical linear regression, controlling for relevant covariates.In unadjusted models, a greater number of childhood trauma exposures were associated with poorer diary- and actigraphy-measured sleep health in adulthood. After adjustment for current stress, depression history, and other sociodemographic covariates, greater childhood trauma remained significantly associated with poorer sleep health (diary: β = -0.20, ΔR = 0.032; actigraphy: β = -0.19, ΔR = 0.027). Trauma exposure after 18 years of age and across the life-span did not relate to diary- or actigraphy-based sleep health.Childhood trauma may affect sleep health in adulthood. These findings align with the growing body of evidence linking childhood trauma to adverse health outcomes later in life.

Objective To conduct a pilot randomized trial of Interpersonal and Social Rhythm Therapy plus Data-Informed Referral (IPSRT + DIR) versus DIR-alone for adolescents at-risk for bipolar disorder (BP). Method Eligible participants included youth (12–18) with a BP parent; youth with BP were excluded. Participants (n = 42) were randomized to receive IPSRT + DIR to treat any psychiatric disorders present at baseline, or DIR-alone. A blind evaluator assessed outcomes at baseline, 3- and 6-months. Participants wore an actigraph to measure sleep/wake patterns for 7 days at baseline and 6-months. Primary outcomes included mood and non-mood symptoms and sleep disturbance. Results Youth randomized to IPSRT + DIR attended approximately half of scheduled IPSRT sessions. Although 33% of DIR-alone youth were referred for mental health services at intake (another 33% were already engaged in services), none initiated new services over follow-up. No youth developed new-onset mood disorder over follow-up. Self- and parent-reported mood and non-mood psychiatric symptoms did not distinguish the groups, although youth in DIR-alone tended to have higher baseline scores on most measures. Per clinician ratings, 1 youth receiving IPSRT + DIR displayed subthreshold hypo/manic symptoms, versus 2 receiving DIR-alone (OR = 14.7, p = 0.03), possibly signaling less subthreshold hypo/manic symptoms, and for fewer weeks (χ2= 11.06, p = 0.0009), over 6-months with IPSRT + DIR. We found a small effect for youth in the IPSRT + DIR group to evidence more WASO at pre-treatment, but less at follow-up (cohen's d = 0.28). Limitations Small sample size limits statistical power, and we are unable to definitively attribute group differences to IPSRT versus greater clinical contact. Ability to examine distal/rare (i.e., BP onset) outcomes was limited. Conclusions Adolescents at-risk for BP present challenges to psychosocial treatment engagement and retention. IPSRT merits further study as an acceptable intervention for at-risk youth, though necessary frequency and intensity to affect outcomes should be examined. The potential to delay or prevent subthreshold hypo/manic symptoms via enhanced sleep continuity is an area for further examination. Future studies with larger samples and extended follow-up can help determine whether IPSRT may delay or prevent syndromal hypo/mania in youth at-risk.

Using evidence-based psychotherapies in community mental health clinics could significantly improve patient functioning. This study explored perceived facilitators and barriers related to implementing interpersonal and social rhythm therapy (IPSRT), an evidence-based psychotherapy for bipolar disorder.The authors conducted 30-minute semistructured interviews with clinic administrators, supervisors, and clinicians from five community mental health clinics focusing on anticipated barriers and facilitators related to implementing IPSRT.Seventeen participants (four administrators, three supervisors, and ten clinicians) completed the interviews. Important barriers to effective implementation included frequent client no-shows, difficulties transitioning from training to practice, and time constraints. Facilitators included support from supervisors and other clinicians, decreased productivity requirements or compensation for time spent while learning IPSRT, and reference materials.Administrators and clinicians expressed similar beliefs about facilitators and barriers related to implementing IPSRT. The challenge of high no-show rates was not identified as a barrier in previous research.

Older women seeking employment often find opportunities limited to low-wage jobs, such as those in retail. We report findings about job placement and starting wages for hourly workers hired at a women's apparel retailer from August 2006 to December 2009. We examine competing hypotheses regarding the role of age in explaining women's job placement and starting wages. Although newly hired women age 55+ earn higher wages and are placed in higher-quality jobs than the youngest women (ages 18-22), they are less likely to be placed in better-quality jobs than their midlife counterparts. Overall, wage differences are largely explained by job quality.

We conducted a randomized, controlled trial comparing the efficacy of an Integrated Risk Reduction Intervention (IRRI) to a control condition with the objective of improving mood stability and psychosocial functioning by reducing cardiometabolic risk factors in overweight/obese patients with bipolar I disorder.A total of 122 patients were recruited from our outpatient services and randomly allocated to IRRI (n = 61) or psychiatric care with medical monitoring (n = 61). Individuals allocated to IRRI received psychiatric treatment and assessment, medical monitoring by a nurse, and a healthy lifestyle program from a lifestyle coach. Those allocated to the control condition received psychiatric treatment and assessment and referral, if indicated, for medical problems. A mixed-effects model was used to examine the impact of the interventions on body mass index (BMI). Exploratory moderator analyses were used to characterize those individuals likely to benefit from each treatment approach.Analyses were conducted on data for the IRRI (n = 58) and control (n = 56) participants with ≥ 1 study visit. IRRI was associated with a significantly greater rate of decrease in BMI (d = -0.51, 95% confidence interval: -0.91 to -0.14). Three variables (C-reactive protein, total cholesterol, and instability of total sleep time) contributed to a combined moderator of faster decrease in BMI with IRRI treatment.Overweight/obese patients with bipolar disorder can make modest improvements in BMI, even when taking medications with known potential for weight gain. Our finding that a combination of three baseline variables provides a profile of patients likely to benefit from IRRI will need to be tested further to evaluate its utility in clinical practice.

Study Objectives The mechanisms linking short sleep duration to cardiovascular disease (CVD) are poorly understood. Emerging evidence suggests that endothelial dysregulation may lie along the causal pathway linking sleep duration to cardiovascular risk, although current evidence in humans is based on cross-sectional studies. Our objective was to evaluate the prospective association between objectively assessed sleep duration and clinical indices of endothelial health. Methods A total of 141 medically healthy adults underwent an overnight laboratory sleep study when they were between the ages of 21 and 60 years. Total sleep time was objectively assessed by polysomnography at study entry. Endothelial health, including brachial artery diameter (BAD) and flow-mediated dilation (FMD), was measured 18.9 ± 4.6 years later. Medical health and psychiatric status were assessed at both time points. Approximately half of the sample had a lifetime history of major depressive disorder. Results In univariate analyses, shorter sleep duration was associated with increased BAD (β = -0.24, p = .004) and decreased FMD (β = 0.17, p = .042). BAD, but not FMD, remained significantly associated with sleep duration after adjusting for sex, age, body mass index (BMI), smoking, diabetes, hypertension, and lifetime history of major depressive disorder (MDD) at T2. The association between sleep duration and BAD was stronger than the association between BAD and an aggregate measure of CVD risk including three or more of the following risk factors: male sex, age ≥ 65 years, smoker, BMI ≥ 30, diabetes, hypertension, and MDD. Conclusions Objectively assessed short sleep duration was prospectively associated with increased BAD over a 12- to 30-year period.

Objective: We demonstrate the utility of the time-varying effect model (TVEM) for the analysis of psychotherapy data, with the aim of elucidating complex patterns of change over time and dynamic associations between constructs of interest. Specifically, we examine the association between depression and co-occurring anxiety in a sample of adults treated with interpersonal psychotherapy (IPT) for depression or a variant designed to address both depression and co-occurring anxiety (IPT-PS, IPT for depression with panic and anxiety symptoms). Method: Seventy-eight (82% female) adult outpatients with major depression and co-occurring anxiety were assessed at each of 16 outpatient treatment sessions using the Hamilton rating scales for depression and anxiety. Results: On average, depressive symptoms declined in a quadratic form over the course of treatment. While the association between anxiety and depression was modest early in treatment, it strengthened over the middle and latter treatment phases. Finally, exploratory analyses suggest that while IPT and IPT-PS were similarly effective in reducing depressive symptoms, IPT-PS may be more effective at uncoupling the association between core anxiety and depressive symptoms. Conclusions: Findings point to the utility of the TVEM for psychotherapy research and the importance of assessing anxiety in the course of treating depression, especially following the initial phase of treatment (i.e., after Session 5).

Interpersonal and Social Rhythm Therapy (IPSRT) delays bipolar disorder (BP) recurrence in adults by stabilizing daily routines and sleep/wake cycles. Because adolescence is a key developmental stage for illness onset and altered social and sleep patterns, this period may prove optimal for intervention with adolescents at-risk for BP. We describe a treatment development trial of IPSRT for adolescents at-risk for BP by virtue of a positive family history. Adolescents with a first-degree relative with BP were evaluated for Axis I psychopathology via semistructured interview, and relatives' BP diagnoses were confirmed via record review. IPSRT consisted of 12 sessions delivered over 6 months. Outcome variables including sleep, mood symptoms, and functioning were assessed via clinician interview and self-/parent-report at pretreatment, 3 months, and posttreatment (6 months). Thirteen adolescents attended at least one IPSRT session. Half of the sample denied Axis I psychopathology at intake; the remainder met criteria for a range of internalizing and externalizing disorders. Families reported high satisfaction with IPSRT, yet, on average, participants attended about half of scheduled sessions. Missed sessions were primarily associated with parental BP illness severity. Data indicate significant change in select sleep/circadian patterns (i.e., less weekend sleeping in and oversleeping) with treatment. Preliminary data suggest the IPSRT focus on stabilizing daily rhythms and interpersonal relationships may be beneficial for adolescents at-risk for BP. Controlled trials with longitudinal follow-up are needed to examine whether early intervention for at-risk youth helps prevent or delay disorder.

Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic external environments. Components of the molecular clock are expressed throughout the brain and are centrally poised to play an important role in brain function. This paper focuses on key issues concerning the relationship among circadian clocks, brain function, and development, and discusses three topic areas: (1) sleep and its relationship to the circadian system; (2) systems development and psychopathology (spanning the prenatal period through late life); and (3) circadian factors and their application to neuropsychiatric disorders. We also explore circadian genetics and psychopathology and the selective pressures on the evolution of clocks. Last, a lively debate is presented on whether circadian factors are central to mood disorders. Emerging from research on circadian rhythms is a model of the interaction among genes, sleep, and the environment that converges on the circadian clock to influence susceptibility to developing psychopathology. This model may lend insight into effective treatments for mood disorders and inform development of new interventions.

In a large, prospective, 8-week open study of 721 outpatients receiving agomelatine treatment for a current major depressive episode (MDE), morningness-eveningness (Composite Scale of Morningness) was assessed before and after treatment to investigate possible changes in morningness-eveningness after treatment and evaluate whether morningness-eveningness at baseline predicted treatment response. A change towards morningness was observed after treatment. This change was greater in responders than non-responders. Moreover, being a morning type at baseline was an independent predictor of response to treatment. Once thought to be a trait variable, morningness-eveningness is a potential treatment target that should be systematically assessed in MDE patients.

The goal of this study was to compare five actigraphy scoring methods in a sample of 18 remitted patients with bipolar disorder. Actigraphy records were processed using five different scoring methods relying on the sleep diary; the event-marker; the software-provided automatic algorithm; the automatic algorithm supplemented by the event-marker; visual inspection (VI) only. The Algorithm and the VI methods differed from the other methods for many actigraphy parameters of interest. Particularly, the Algorithm method yielded longer sleep duration, and the VI method yielded shorter sleep latency compared to the others methods. The present findings provide guidance for the selection of signal processing method based on sleep parameters of interest, time-cue sources and availability, and related scoring time costs for the study.

Objective Some reports suggest an increase in suicide ideations and behaviors in patients treated with antidepressants. This is an analysis of the impact of fluoxetine on suicide ideations in outpatients with minor depressive disorder. Methods Research subjects were adult outpatients with minor depressive disorder ( N = 162), who received fluoxetine or placebo in a prospective, 12-week, double-blind randomized trial. The research participants were evaluated weekly with standard rating scales that included four suicide-related items: item 3 of the Hamilton Rating Scale for Depression (HRSD), item 18 of Inventory of Depressive Symptomatology (IDS-C), and items 15 and 59 of the Hopkins Symptom Checklist (SCL-90). Clinically significant intensification of suicide ideation was defined as an increase of ≥2 points on any of these items. Results Overall 60/162 subjects (37%) had an increase of ≥1 point during treatment and 17/162 (10.5%) of ≥2 points on at least one suicide item, with 12/81 (14.8%) placebo and 5/81 (6.2%) fluoxetine-treated subjects having a ≥2 point gain. Of the study participants with baseline suicide ideation, 9/22 (40.9%) placebo and 3/24 (12.5%) fluoxetine treated had ≥2 point increase ( p = 0.04). Survival analysis revealed that subjects on placebo were significantly more likely ( p = 0.050) to experience a ≥2 point increase on one or more item, a difference that emerged early and continued throughout the 12-week trial. Conclusions Compared to placebo, fluoxetine was not associated with a clinically significant increase in suicide ideation among adults with minor depressive disorder during 12 weeks of treatment.

Objectives Disruption of circadian function has been observed in several human disorders, including bipolar disorder (BD). Research into these disorders can be facilitated by human cellular models that evaluate external factors (zeitgebers) that impact circadian pacemaker activity. Incorporating a firefly luciferase reporter system into human fibroblasts provides a facile, bioluminescent readout that estimates circadian phase, while leaving the cells intact. We evaluated whether this system can be adapted to clinical BD research and whether it can incorporate zeitgeber challenge paradigms. Methods Fibroblasts from patients with bipolar I disorder (BD-I) (n = 13) and controls (n = 12) were infected ex vivo with a lentiviral reporter incorporating the promoter sequences for Bmal1, a circadian gene to drive expression of the firefly luciferase gene. Following synchronization, the bioluminescence was used to estimate period length. Phase response curves (PRCs) were also generated following forskolin challenge and the phase response patterns were characterized. Results Period length and PRCs could be estimated reliably from the constructs. There were no significant case-control differences in period length, with a nonsignificant trend for differences in PRCs following the phase-setting experiments. Conclusions An ex vivo cellular fibroblast-based model can be used to investigate circadian function in BD-I. It can be generated from specific individuals and this could usefully complement ongoing circadian clinical research.

Cardiovascular risk factors, such as abdominal obesity and obesity in general, are very prevalent among patients with bipolar disorder (BD). Although long-term use of psychotropic medications is an important determinant of these risk factors, other evidence suggests that early development may interact with the mood disorder diathesis to exponentially increase the risk of obesity. The goal of our study was to test whether season of birth is associated with adult body mass index (BMI) and abdominal obesity in individuals with bipolar disorder. We compared season of birth effects on BMI in 375 adult patients with bipolar disorder and 196 adult patients with unipolar major depression. We found a significant season of birth effect on BMI in patients with bipolar disorder, but not unipolar. In patients with bipolar disorder, season of birth was also associated with waist circumference, with a stronger effect in males. Season of birth affects adult BMI and waist circumference in patients with bipolar disorder, but not in patients with unipolar depression. Our results suggest that early environmental factors, yet to be identified, interact with specific neurobiological features of bipolar disorder to determine stable traits and disease risk factors in adult life.

This study examined whether sleep disturbance predicted or moderated responses to psychotherapy in participants who participated in STEP-BD, a national, multisite study that examined the effectiveness of different treatment combinations for bipolar disorder. Participants received either a brief psychosocial intervention called collaborative care (CC; n = 130) or intensive psychotherapy (IP; n = 163), with study-based pharmacotherapy. Participants (N = 243) were defined as current (past week) short sleepers (

Dynamic psychological processes are most often assessed using self-report instruments. This places a constraint on how often and for how long data can be collected due to the burden placed on human participants. Smartphones are ubiquitous and highly personal devices, equipped with sensors that offer an opportunity to measure and understand psychological processes in real-world contexts over the long term. In this article, we present a novel smartphone approach to address the limitations of self-report in bipolar disorder where mood and activity are key constructs. We describe the development of MoodRhythm, a smartphone application that incorporates existing self-report elements from interpersonal and social rhythm therapy, a clinically validated treatment, and combines them with novel inputs from smartphone sensors. We reflect on lessons learned in transitioning from an existing self-report instrument to one that involves smartphone sensors and discuss the potential impact of these changes on the future of psychological assessment.

Background: Few studies have prospectively examined the relationships of sleep with symptoms and functioning in bipolar disorder. Methods: The present study examined concurrent and prospective associations between total sleep time (TST) and sleep variability (SV) with symptom severity and functioning in a cohort of DSM-IV bipolar patients (N = 468) participating in the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), all of whom were recovered at study entry. Results: Concurrent associations at study entry indicated that shorter TST was associated with increased mania severity, and greater SV was associated with increased mania and depression severity. Mixed-effects regression modeling was used to examine prospective associations in the 196 patients for whom follow-up data were available. Consistent with findings at study entry, shorter TST was associated with increased mania severity, and greater SV was associated with increased mania and depression severity over 12 months. Discussion: These findings highlight the importance of disrupted sleep patterns in the course of bipolar illness. © 2011 Elsevier B.V. All rights reserved.

The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n = 182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile.

OBJECTIVES: Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. METHODS: Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. RESULTS: Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. CONCLUSION: Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

Objective Two-generation studies demonstrate that treating maternal depression benefits school-age children. Although mothers prefer psychotherapy to medication, little is known about how psychotherapy for maternal depression affects offspring, especially in very high-risk families in which both mothers and children concurrently meet syndromal criteria for psychiatric disorders. This trial evaluated the effects of 2 brief psychotherapies for maternal depression on very high-risk families. Method Mothers with major depressive disorder were randomly assigned to 9 sessions of either brief interpersonal psychotherapy for mothers (IPT-MOMS; n = 85) or brief supportive psychotherapy (BSP; n = 83). Independent assessors evaluated mothers and their children, ages 7 to 18 years, diagnosed with at least 1 internalizing disorder, every 3 months over the course of 1 year. Results Symptoms and functioning of mothers and children improved significantly over time, with no between-group differences. However, children of mothers assigned to BSP had more outpatient mental health visits and were more likely to receive antidepressant medication. Mothers reported greater satisfaction with IPT-MOMS than BSP. Improvement in mothers' depressive symptoms was associated with improvement in child functioning in time-lagged fashion, with children improving 3 to 6 months after mothers improved. Antidepressant medication use and number of mental health visits received by children did not affect outcomes. Conclusion IPT-MOMS and BSP demonstrated comparable beneficial effects on maternal depression. Children's functioning improved following maternal improvement, independent of youths' treatment. Children of mothers randomized to IPT-MOMS, compared with BSP, achieved comparable outcomes despite less follow-up treatment. Observation of lagged association between maternal improvement and change in child functioning should influence treatment planning for families. Clinical trial registration information —Psychotherapy for Depressed Mothers of Psychiatrically Ill Children; http://clinicaltrials.gov/; NCT00919594.

BackgroundLittle is known about predictors of recovery from bipolar depression.AimsWe investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression.MethodA total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n= 141) or a brief psychoeducational intervention (n= 111). All analyses were by intention-to-treat.ResultsDegree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression.ConclusionsAffective instability may be a clinically relevant characteristic that influences the course of bipolar depression.

Background Individuals diagnosed with bipolar 1 disorder (BP1), bipolar 2 disorder (BP2), or major depressive disorder (MDD) experience varying levels of depressive and (hypo)manic symptoms. Clarifying symptom heterogeneity is meaningful, as even subthreshold symptoms may impact quality of life and treatment outcome. The MOODS Lifetime self-report instrument was designed to capture the full range of depressive and (hypo)manic characteristics. Methods This study applied clustering methods to 347 currently depressed adults with MDD, BP2, or BP1 to reveal naturally occurring MOODS subgroups. Subgroups were then compared on baseline clinical and demographic characteristics and as well as depressive and (hypo)manic symptoms over twenty weeks of treatment. Results Four subgroups were identified: (1) high depressive and (hypo)manic symptoms (N=77, 22%), (2) moderate depressive and (hypo)manic symptoms (N=115, 33%), (3) low depressive and moderate (hypo)manic symptoms (N=82, 24%), and (4) low depressive and (hypo)manic symptoms (N=73, 21%). Individuals in the low depressive/moderate (hypo)manic subgroup had poorer quality of life and greater depressive symptoms over the course of treatment. Individuals in the high and moderate severity subgroups had greater substance use, longer duration of illness, and greater (hypo)manic symptoms throughout treatment. Treatment outcomes were primarily driven by individuals diagnosed with MDD. Limitations The sample was drawn from three randomized clinical trials. Validation is required for this exploratory study. Conclusions After validation, these subgroups may inform classification and personalized treatment beyond categorical diagnosis.

Background Telephone-administered psychotherapies (T-P) provided as an adjunct to antidepressant medication may improve response rates in major depressive disorder (MDD). The goal of this study was to compare telephone-administered social rhythm therapy (T-SRT) and telephone-administered intensive clinical management (T-ICM) as adjuncts to antidepressant medication for MDD. A secondary goal was to compare T-P with Treatment as Usual (TAU) as adjunctive treatment to medication for MDD. Methods 221 adult out-patients with MDD, currently depressed, were randomly assigned to 8 sessions of weekly T-SRT ( n =110) or T-ICM ( n =111), administered as an adjunct to agomelatine. Both psychotherapies were administered entirely by telephone, by trained psychologists who were blind to other aspects of treatment. The 221 patients were a posteriori matched with 221 depressed outpatients receiving TAU (controls). The primary outcome measure was the percentage of responders at 8 weeks post-treatment. Results No significant differences were found between T-SRT and T-ICM. But T-P was associated with higher response rates (65.4% vs 54.8%, p =0.02) and a trend toward higher remission rates (33.2% vs 25.1%; p =0.06) compared to TAU. Limitations Short term study. Conclusions This study is the first assessing the short-term effects of an add-on, brief, telephone-administered psychotherapy in depressed patients treated with antidepressant medication. Eight sessions of weekly telephone-delivered psychotherapy as an adjunct to antidepressant medication resulted in improved response rates relative to medication alone.

BackgroundPatients with major depressive disorder (MDD) present with highly heterogeneous symptom profiles. We aimed to examine whether individual differences in amygdala activity to emotionally salient stimuli were related to heterogeneity in lifetime levels of depressive and subthreshold manic symptoms among adults with MDD.MethodWe compared age- and gender-matched adults with MDD (n = 26) with healthy controls (HC, n = 28). While undergoing functional magnetic resonance imaging, participants performed an implicit emotional faces task: they labeled a color flash superimposed upon initially neutral faces that dynamically morphed into one of four emotions (angry, fearful, sad, happy). Region of interest analyses examined group differences in amygdala activity. For conditions in which adults with MDD displayed abnormal amygdala activity versus HC, within-group analyses examined amygdala activity as a function of scores on a continuous measure of lifetime depression-related and mania-related pathology.ResultsAdults with MDD showed significantly greater right-sided amygdala activity to angry and happy conditions than HC (p p = 0.002).ConclusionsAmong depressed adults with MDD, lifetime features of subthreshold mania were associated with abnormally elevated amygdala activity to emerging happy faces. These findings are a first step toward identifying biomarkers that reflect individual differences in neural mechanisms in MDD, and challenge conventional mood disorder diagnostic boundaries by suggesting that some adults with MDD are characterized by pathophysiological processes that overlap with bipolar disorder.

OBJECTIVE: Multiple studies indicate that bipolar disorders are often underrecognized, misdiagnosed, and incorrectly treated. The aim of the present report is to determine which combination of clinical, demographic, and psychopathological factors and corresponding cutoff scores best discriminate patients with unipolar disorder from those with bipolar disorders. METHOD: The study sample includes outpatients and inpatients (N = 1,158) participating in 5 studies carried out in the United States and Italy between October 2001 and March 2008, one of which was a randomized clinical trial. Diagnostic assessment was carried out with the SCID, which allows diagnoses to be made according to DSM-IV-TR criteria. Using an exploratory statistical approach based on a classification tree, we employed 5 mania spectrum factors and 6 depression spectrum factors derived from the Mood Spectrum Self-Report Instrument (MOODS-SR) in combination with demographic and clinical characteristics to discriminate participants with unipolar versus bipolar disorders. RESULTS: The psychomotor activation factor, assessing the presence of thought acceleration, distractibility, hyperactivity, and restlessness for 1 or more periods of at least 3 to 5 days in the lifetime, identified subgroups with an increasing likelihood of bipolar disorder diagnosis. Mixed instability and suicidality contributed to further subtyping the sample into mutually exclusive groups, characterized by a different likelihood of receiving a diagnosis of bipolar disorder. Of the demographic and clinical characteristics included in the analysis, only sex proved to be useful to improve the discrimination. CONCLUSIONS: The psychomotor activation factor proved to be the most potent discriminator of those with unipolar versus bipolar diagnoses. The items that constitute this factor, together with those that constitute the mixed instability, suicidality, and euphoria factors, might be useful in making the differential diagnosis.

In this review we explore recent developments in computerized adaptive diagnostic screening and computerized adaptive testing for the presence and severity of mental health disorders such as depression, anxiety, and mania. The statistical methodology is unique in that it is based on multidimensional item response theory (severity) and random forests (diagnosis) instead of traditional mental health measurement based on classical test theory (a simple total score) or unidimensional item response theory. We show that the information contained in large item banks consisting of hundreds of symptom items can be efficiently calibrated using multidimensional item response theory, and the information contained in these large item banks can be precisely extracted using adaptive administration of a small set of items for each individual. In terms of diagnosis, computerized adaptive diagnostic screening can accurately track an hour-long face-to-face clinician diagnostic interview for major depressive disorder (as an example) in less than a minute using an average of four questions with unprecedented high sensitivity and specificity. Directions for future research and applications are discussed.

Objective: Individuals with bipolar disorder experience a disproportionately high incidence of medical co-morbidity and obesity. These health-related problems are a barrier to recovery from mood episodes and have been linked with unfavorable responses to pharmacological treatment. However, little is known about whether and how these characteristics affect responses to adjunctive psychotherapy. Method: Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy plus pharmacotherapy with collaborative care (a three-session psycho-educational intervention) plus pharmacotherapy. We conducted a post-hoc analysis to evaluate whether medical burden and body mass index predicted and/or moderated the likelihood of recovery and time until recovery from a depressive episode among patients in the two treatments. Results: Participants who had medical co-morbidity and body mass index data constituted 199 of the 293 patients in the original Systematic Treatment Enhancement Program for Bipolar Disorder trial. Higher medical burden predicted a lower likelihood of recovery from depression in both treatment conditions (odds ratio = 0.89), but did not moderate responses to intensive psychotherapy vs collaborative care. Intensive psychotherapy yielded superior recovery rates for individuals of normal body mass index (odds ratio= 2.39) compared with collaborative care, but not among individuals who were overweight or obese. Conclusion: Medical co-morbidity and body weight impacts symptom improvement and attention to this co-morbidity may inform the development of more personalized treatments for bipolar disorder.

Background We sought to address how predictors and moderators of psychotherapy for bipolar depression – identified individually in prior analyses – can inform the development of a metric for prospectively classifying treatment outcome in intensive psychotherapy (IP) versus collaborative care (CC) adjunctive to pharmacotherapy in the Systematic Treatment Enhancement Program (STEP-BD) study. Methods We conducted post-hoc analyses on 135 STEP-BD participants using cluster analysis to identify subsets of participants with similar clinical profiles and investigated this combined metric as a moderator and predictor of response to IP. We used agglomerative hierarchical cluster analyses and k-means clustering to determine the content of the clinical profiles. Logistic regression and Cox proportional hazard models were used to evaluate whether the resulting clusters predicted or moderated likelihood of recovery or time until recovery. Results The cluster analysis yielded a two-cluster solution: 1) “less-recurrent/severe” and 2) “chronic/recurrent.” Rates of recovery in IP were similar for less-recurrent/severe and chronic/recurrent participants. Less-recurrent/severe patients were more likely than chronic/recurrent patients to achieve recovery in CC (p=.040, OR=4.56). IP yielded a faster recovery for chronic/recurrent participants, whereas CC led to recovery sooner in the less-recurrent/severe cluster (p=.034, OR=2.62). Limitations Cluster analyses require list-wise deletion of cases with missing data so we were unable to conduct analyses on all STEP-BD participants. Conclusions A well-powered, parametric approach can distinguish patients based on illness history and provide clinicians with symptom profiles of patients that confer differential prognosis in CC vs. IP.

Insomnia and objectively measured sleep disturbances predict poor treatment outcomes in patients with major depressive disorder (MDD). However, prior research has utilized individual clinical trials with relatively small sample sizes and has focused on insomnia symptoms or objective measures, but not both. The present study is a secondary analysis that examines the degree to which insomnia, objective sleep disturbances, or their combination predicts depression remission following pharmacotherapy and/or psychotherapy treatment.Participants were 711 depressed (DSM criteria) patients drawn from 6 clinical trials. Remission status, defined as a score of ≤ 7 on the Hamilton Depression Rating Scale (HDRS) over 2 consecutive months, served as the primary outcome. Insomnia was assessed via the 3 sleep items on the HDRS. Objectively measured short sleep duration (total sleep time ≤ 6 hours) and prolonged sleep latency (30 minutes) or wakefulness after sleep onset (30 minutes) were derived from in-laboratory polysomnographic sleep studies. Logistic regression predicted the odds of nonremission according to insomnia, each of the objective sleep disturbances, or their combination, after adjusting for age, sex, treatment modality, and baseline depressive symptoms.Prolonged sleep latency alone (OR = 3.53; 95% CI, 1.28-9.73) or in combination with insomnia (OR = 2.11; 95% CI, 1.13-3.95) predicted increased risk of nonremission. In addition, insomnia and sleep duration individually and in combination were each associated with a significantly increased risk of nonremission (P values.05).Findings suggest that objectively measured prolonged sleep latency and short sleep duration independently or in conjunction with insomnia are risk factors for poor depression treatment outcome.

Background: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. Methods: The study sample includes 225 patients who entered the 6-month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score Z15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. Results: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. Conclusions: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience. Depression and Anxiety 28:955–962, 2011. r 2011 Wiley Periodicals, Inc.

More than half of the older adults respond only partially to first-line antidepressant pharmacotherapy. Our objective was to test the hypothesis that a depression-specific psychotherapy, Interpersonal Psychotherapy (IPT), when used adjunctively with escitalopram, would lead to a higher rate of remission and faster resolution of symptoms in partial responders than escitalopram with depression care management (DCM).We conducted a 16-week randomized clinical trial of IPT and DCM in partial responders to escitalopram, enrolling 124 outpatients aged 60 and older. The primary outcome, remission, was defined as three consecutive weekly scores of 7 or less on the Hamilton rating scale for depression (17-item). We conducted Cox regression analyses of time to remission and logistic modeling for rates of remission. We tested group differences in Hamilton depression ratings over time via mixed-effects modeling.Remission rates for escitalopram with IPT and with DCM were similar in intention-to-treat (IPT vs. DCM: 58 [95% CI: 46, 71] vs. 45% [33,58]; p = 0.14) and completer analyses (IPT vs. DCM: 58% [95% CI: 44,72] vs. 43% [30,57]; p = 0.20). Rapidity of symptom improvement did not differ in the two treatments.No added advantage of IPT over DCM was shown. DCM is a clinically useful strategy to achieve full remission in about 50% of partial responders.

OBJECTIVE: Few studies have compared treatment outcomes of African-American, Hispanic, and non-Hispanic white patients with bipolar disorder. The U.S. Systematic Treatment Enhancement Program for Bipolar Disorder compared one-year outcomes for bipolar I or II disorder from each of these racial-ethnic groups. METHODS: African Americans (N=155) were retrospectively compared with a matched group of non-Hispanic whites (N=729), and Hispanics (N=152) were compared with a separate matched group of non-Hispanic whites (N=822). Response and recovery outcomes were examined. Survival analysis was used to compare time to treatment response for depression (Montgomery-Asberg Depression Rating Scale) and mania (Young Mania Rating Scale) as well as global assessment of functioning (Global Assessment of Functioning). RESULTS: For manic and depressive symptoms, time to response and proportion of responders were similar across groups. Over the study year the proportion of days well was similar across groups. A smaller proportion of African Americans met criteria for improved global functioning. Depression response among African Americans with psychotic symptoms was slower than the response among African Americans without psychotic symptoms and among non-Hispanic whites with or without psychotic symptoms. No differences between Hispanics and non-Hispanic whites in response times and recovery were observed. CONCLUSIONS: Results are consistent with U.S. clinical trials for other psychiatric disorders, which have reported similar outcomes for ratings of primary symptoms. Baseline psychotic symptoms are likely a significant contributor when African Americans with bipolar disorder are slow to recover. These results may be less generalizable to uninsured patients.

The purpose of this study was to characterize escitalopram population pharmacokinetics (PK) in patients treated for major depression in a cross-national, US-Italian clinical trial. Data from the 2 sites participating in this trial, conducted at Pittsburgh (United States) and Pisa (Italy), were used. Patients received 5, 10, 15, or 20 mg of escitalopram daily for a minimum of 32 weeks. Nonlinear mixed effects modeling was used to model the PK characteristics of escitalopram. One- and 2-compartment models with various random effect implementations were evaluated during model development. Objective function values and goodness-of-fit plots were used as model selection criteria. CYP2C19 genotype, age, weight, body mass index, sex, race, and clinical site were evaluated as possible covariates. In total, 320 plasma concentrations from 105 Pittsburgh patients and 153 plasma concentrations from 67 Pisa patients were available for the PK model development. A 1-compartmental model with linear elimination and proportional error best described the data. Apparent clearance (CL/F) and volume of distribution (V/F) for escitalopram without including any covariates in the patient population were 23.5 L/h and 884 L, respectively. CYP2C19 genotype, weight, and age had a significant effect on CL/F, and patient body mass index affected estimated V/F. Patients from Pisa, Italy, had significantly lower clearances than patients from Pittsburgh that disappeared after controlling for patient CYP2C19 genotype, age, and weight. Postprocessed individual empirical Bayes estimates on clearance for the 172 patients show that patients without allele CYP2C19(*)2 or (*)3 (n = 82) cleared escitalopram 33.7% faster than patients with heterogeneous or homogeneous (*)2 or (*)3 ((*)17/(*)2, (*)17/(*)3, (*)1/(*)2, (*)1/(*)3, (*)2/(*)2, (*)2/(*)3, and (*)3/(*)3, n = 46). CL/F significantly decreased with increasing patient age. Patients younger than 30 years (n = 45) cleared escitalopram 20.7% and 42.7% faster than patients aged 30 to 50 years (n = 84) and older than 50 years of age (n = 43), respectively. CYP2C19 genotype, age, and weight strongly influenced the CL/F of escitalopram. These variables may affect patient tolerance of this antidepressant and may provide important information in the effort to tailor treatments to patients' individual needs.

Adolescents, elderly persons, African Americans, and rural residents with bipolar disorder are less likely than their middle-aged, white, urban counterparts to be diagnosed, receive adequate treatment, remain in treatment once identified, and have positive outcomes. The Bipolar Disorder Center for Pennsylvanians (BDCP) study was designed to address these disparities. This report highlights the methods used to recruit, screen, and enroll a cohort of difficult-to-recruit individuals with bipolar disorder.Study sites included three specialty clinics for bipolar disorder in a university setting and a rural behavioral health clinic. Study operations were standardized, and all study personnel were trained in study procedures. Several strategies were used for recruitment.It was possible to introduce the identical assessment and screening protocol in settings regardless of whether they had a history of implementing research protocols. This protocol was also able to be used across the age spectrum, in urban and rural areas, and in a racially diverse cohort of participants. Across the four sites 515 individuals with bipolar disorder were enrolled as a result of these methods (69 African Americans and 446 non-African Americans). Although clinical characteristics at study entry did not differ appreciably between African Americans and non-African Americans, the pathways into treatment differed significantly.Rigorous recruitment and assessment procedures can be successfully introduced in different settings and with different patient cohorts, thus facilitating access to high-quality treatment for individuals who frequently do not receive appropriate care for bipolar disorder.

In this paper we present a brief measure of caregiver burden, the Mood Disorder Burden Index (MDBI), for use with family members and close friends of adults with major depressive disorder (MDD) or bipolar disorder (BD). The MDBI assesses burden in three core domains (patients’ mood symptoms, caregivers’ worry about the future, and caregivers’ interpersonal difficulties with the patient) and includes an optional module that assesses caregiver burden associated with patients’ pharmacotherapy or psychotherapy. The MDBI was administered to caregivers of older individuals (i.e., 58 years and older) with MDD (n = 123) or BD (n = 38 who were receiving treatment through a research study. Analyses indicated evidence of convergent and discriminant validity of the new measure well as internal consistency within both caregiver groups. It will be important for future research to administer the MDBI to caregivers of middle-aged and older patients as well as those receiving treatment through inpatient settings or community outpatient clinics.

We explored whether obesity in patients with bipolar disorder is associated with their chronotype. A group of 29 patients with bipolar I disorder, not currently experiencing an affective episode, were assessed for total body fat, mood symptoms, and self-reported circadian chronotype and sleep quality. Chronotype explained 19% of the variance in body fat, after age, sex, mood state, and sleep quality were accounted for. This association suggested that evening chronotype patients have a higher percentage of total body fat. Evening chronotype could be a proxy for as yet unknown specific causes of the high rate of obesity and obesity-related diseases in bipolar disorder.

Bipolar disorder (BD) has been classically described as one of episodic mood disturbances. New evidence suggests that a chronic course and multisystem involvement is the rule, rather than the exception, and that together with disturbances of circadian rhythms, mood instability, cognitive impairment, a high rate of medical burden is often observed. The current diagnostic approach for BD neither describes the multisystem involvement that the recent literature has highlighted nor points toward potential predictors of long- term outcome. In light of the new evidence that the long-term course of BD is associated with a high prevalence of psychiatric comorbidity and an increased mortality from medical disease, we propose a multidimensional approach that includes several symptom domains, namely affective instability, circadian rhythm dysregulation, and cognitive and executive dysfunction, presenting in various combinations that give shape to each individual presentation, and offers potential indicators of overall long-term prognosis.

Even low levels of residual symptoms are known to increase the risk of relapse and early recurrence of major depression. It is not known if ongoing psychotherapy lessens this risk. We therefore examined the impact of persistent symptoms, including mood, insomnia, and anxiety symptoms, on time to recurrence in women receiving maintenance interpersonal psychotherapy (IPT-M) for recurrent depression.We analyzed data on 131 women aged 20-60 from a 2-year randomized trial of weekly versus twice-monthly versus monthly IPT-M. Participants achieved remission with IPT alone (n=99) or IPT plus sequential antidepressant medication (n=32). Medications were tapered before starting maintenance treatment. Residual symptoms were assessed with the Hamilton Rating Scale for Depression (HRSD; total score and subscales); insomnia was also assessed in 76 women with the Pittsburgh Sleep Quality Index (PSQI). Data analyses used Cox proportional hazards regression models.Neither overall burden of residual symptoms (HRSD total score), nor HRSD mood and anxiety subscale scores predicted recurrence during ongoing IPT-M. In contrast, persistent insomnia measured both by the HRSD-17 insomnia subscale and the PSQI predicted recurrence. Women with persistent insomnia who required sequential pharamacotherapy had the highest recurrence rate (65%) compared to women requiring sequential treatment without insomnia (13%), or women who had recovered with IPT alone but had persistent insomnia (21%) or no insomnia (18%).Persistent insomnia following the recovery from an episode of recurrent major depression is associated with increased risk of recurrence despite maintenance psychotherapy, particularly for those withdrawn from antidepressant medication.