Long day's journey into sleep.

My long day's journey into sleep began as an adolescent trying to manage my evening chronotype. The relief, I felt when my undergraduate finals were scheduled at night and as a medical student being able to select psychiatry over surgery deepened my interest in sleep and chronobiology. That interest was allowed to flourish at the National Institute of Mental Health and then at Yale Medical School in setting up a sleep laboratory. The decision to move to the University of Pittsburgh in 1973 led to a 42-year adventure in which we were able to initiate research efforts on the psychobiology of depression. Our interest in social zeitgebers (daily routines) led directly to the development and testing of a treatment intervention for mood disorders, interpersonal, and social rhythm therapy. Our continued emphasis on sleep and circadian rhythms convinced us that sleep and circadian factors were central to all of health, based on the importance of connectivity between sleep and major metabolic and cell functions. This ongoing research motivated our strong desire to study the developmental aspects of sleep. Our success was influenced immensely by the presence of young scientists and a strong subsequent interest in career mentoring. Finally, as we left Pittsburgh in 2015, we became involved in the field of continuous objective monitoring using the commercial smartphone's behavioral sensing capabilities. Our journey is not over. We hope to explore the potential of these remarkable devices to improve our understanding of sleep/wake and circadian factors across all of health.

Corrigendum: Personalized digital intervention for depression based on social rhythm principles adds significantly to outpatient treatment.

[This corrects the article DOI: 10.3389/fdgth.2022.870522.].

Personalized digital intervention for depression based on social rhythm principles adds significantly to outpatient treatment.

We conducted a 16-week randomized controlled trial in psychiatric outpatients with a lifetime diagnosis of a mood and/or anxiety disorder to measure the impact of a first-of-its-kind precision digital intervention software solution based on social rhythm regulation principles. The full intent-to-treat (ITT) sample consisted of 133 individuals, aged 18-65. An exploratory sub-sample of interest was those individuals who presented with moderately severe to severe depression at study entry (baseline PHQ-8 score ≥15; N = 28). Cue is a novel digital intervention platform that capitalizes on the smartphone's ability to continuously monitor depression-relevant behavior patterns and use each patient's behavioral data to provide timely, personalized "micro-interventions," making this the first example of a precision digital intervention of which we are aware. Participants were randomly allocated to receive Cue plus care-as-usual or digital monitoring only plus care as usual. Within the full study and depressed-at-entry samples, we fit a mixed effects model to test for group differences in the slope of depressive symptoms over 16 weeks. To account for the non-linear trajectory with more flexibility, we also fit a mixed effects model considering week as a categorical variable and used the resulting estimates to test the group difference in PHQ change from baseline to 16 weeks. In the full sample, the group difference in the slope of PHQ-8 was negligible (Cohen's d = -0.10); however, the Cue group demonstrated significantly greater improvement from baseline to 16 weeks (p = 0.040). In the depressed-at-entry sample, we found evidence for benefit of Cue. The group difference in the slope of PHQ-8 (Cohen's d = -0.72) indicated a meaningfully more rapid rate of improvement in the intervention group than in the control group. The Cue group also demonstrated significantly greater improvement in PHQ-8 from baseline to 16 weeks (p = 0.009). We are encouraged by the size of the intervention effect in those who were acutely ill at baseline, and by the finding that across all participants, 80% of whom were receiving pharmacotherapy, we observed significant benefit of Cue at 16 weeks of treatment. These findings suggest that a social rhythm-focused digital intervention platform may represent a useful and accessible adjunct to antidepressant treatment (https://clinicaltrials.gov/ct2/show/NCT03152864?term=ellen+frank&draw=2&rank=3).

A randomized pilot study of Rhythms And You (RAY): An internet-based program for bipolar disorder administered with and without clinical helper support in primary care.

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.

Development and Validation of Computerized Adaptive Assessment Tools for the Measurement of Posttraumatic Stress Disorder Among US Military Veterans.

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.

Dr. Gibbons et al. Reply.

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.

Computerized Adaptive Tests for Rapid and Accurate Assessment of Psychopathology Dimensions in Youth.

OBJECTIVE: At least half of youths with mental disorders are unrecognized and untreated. Rapid, accurate assessment of child mental disorders could facilitate identification and referral and potentially reduce the occurrence of functional disability that stems from early-onset mental disorders. METHOD: Computerized adaptive tests (CATs) based on multidimensional item response theory were developed for depression, anxiety, mania/hypomania, attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder, and suicidality, based on parent and child ratings of 1,060 items each. In phase 1, CATs were developed from 801 participants. In phase 2, predictive, discriminant, and convergent validity were tested against semi-structured research interviews for diagnoses and suicidality in 497 patients and 104 healthy controls. Overall strength of association was determined by area under the receiver operating characteristic curve (AUC). RESULTS: The child and parent independently completed the Kiddie-Computerized Adaptive Tests (K-CATs) in a median time of 7.56 and 5.03 minutes, respectively, with an average of 7 items per domain. The K-CATs accurately captured the presence of diagnoses (AUCs from 0.83 for generalized anxiety disorder to 0.92 for major depressive disorder) and suicidal ideation (AUC = 0.996). Strong correlations with extant measures were found (r ≥ 0.60). Test-retest reliability averaged r = 0.80. CONCLUSION: These K-CATs provide a new approach to child psychopathology screening and measurement. Testing can be completed by child and parent in less than 8 minutes and yields results that are highly convergent with much more time-consuming structured clinical interviews and dimensional severity assessment and measurement. Testing of the implementation of the K-CAT is now indicated.

The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology.

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.

Integrating Patients' Expectations into the Management of Their Depression: Report of a Symposium at the European College of Neuropsychopharmacology Congress.

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.

The impact of substance use disorders on recovery from bipolar depression: Results from the Systematic Treatment Enhancement Program for Bipolar Disorder psychosocial treatment trial.

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.

Early intervention for adolescents at-risk for bipolar disorder: A pilot randomized trial of Interpersonal and Social Rhythm Therapy (IPSRT).

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.

Association analysis of successive events data in the presence of competing risks.

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.

Psychotherapy Alone and Combined With Medication as Treatments for Bipolar II Depression: A Randomized Controlled Trial.

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.

The Relationship Between Childhood Trauma and Poor Sleep Health in Adulthood.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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: ß = -0.20, ΔR = 0.032; actigraphy: ß = -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. CONCLUSIONS: 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.

Smart phone technologies and ecological momentary data: is this the way forward on depression management and research?

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.

Development of a Computerized Adaptive Test Suicide Scale-The CAT-SS.

OBJECTIVE: Current suicide risk screening and measurement are inefficient, have limited measurement precision, and focus entirely on suicide-related items. For this study, a psychometric harmonization between related suicide, depression, and anxiety symptom domains that provides a more balanced and complete spectrum of suicidal symptomatology was developed. The objective of this article is to describe the results of the early stages of computerized adaptive testing development for a suicide scale and pave the way for the final stage of validation. METHODS: Data from psychiatric outpatients at the University of Pittsburgh and a community health clinic were collected from January 2010 through June 2012. 789 participants were enrolled in the calibration phase; 70% were female, and 30% were male. The rate of major depressive disorder as diagnosed by DSM-5 was 47%. The item bank contained 1,008 items related to depression, anxiety, and mania, including 11 suicide items. Data were analyzed using a bifactor model to identify a core dimension between suicidal ideation, depression, anxiety, and mania items. A computerized adaptive test was developed via simulation from the actual complete item responses in 308 subjects. RESULTS: 111 items were identified that provided an extension of suicidality assessment to include statistically related responses from depression and anxiety domains that are syndromally associated with suicidality. All items had high loadings on the primary suicide dimension (average = 0.67; range, 0.49-0.88). Analyses revealed that a mean of 10 items (5-20) had a correlation of 0.96 with the 111-item scale, with a precision of 5 points on a 100-point scale metric. Preliminary validation data based on 290 clinician interviews revealed a 52-fold increase in the likelihood of current suicidal ideation across the range of the Computerized Adaptive Test Suicide Scale (CAT-SS). CONCLUSIONS: The CAT-SS is able to accurately measure the latent suicide dimension with a mean of 10 items in approximately 2 minutes. Further validation against an independent clinician-administered assessment of suicide risk (ideation and attempts) and prediction of suicidal behavior is underway.

Objective Sleep Duration Is Prospectively Associated With Endothelial Health.

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 (ß = -0.24, p = .004) and decreased FMD (ß = 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.

Do Sleep Disturbances Predict or Moderate the Response to Psychotherapy in Bipolar Disorder?

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 (<6 hours/night), normal sleepers (6.5-8.5 hours/night), and long sleepers (≥9 hours/night), according to reported average nightly sleep duration the week before randomization. Sleep disturbances did not predict the likelihood of recovery nor time until recovery from a depressive episode. There was no difference in recovery rates between IP versus CC for normal sleepers, and medium effect sizes were observed for differences in short and long sleepers. In this study, sleep did not play a major role in predicting or moderating response to psychotherapy in bipolar disorder.