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.

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.

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.

The computerized adaptive diagnostic test for major depressive disorder (CAD-MDD): a screening tool for depression.

OBJECTIVE: To develop a computerized adaptive diagnostic screening tool for depression that decreases patient and clinician burden and increases sensitivity and specificity for clinician-based DSM-IV diagnosis of major depressive disorder (MDD). METHOD: 656 individuals with and without minor and major depression were recruited from a psychiatric clinic and a community mental health center and through public announcements (controls without depression). The focus of the study was the development of the Computerized Adaptive Diagnostic Test for Major Depressive Disorder (CAD-MDD) diagnostic screening tool based on a decision-theoretical approach (random forests and decision trees). The item bank consisted of 88 depression scale items drawn from 73 depression measures. Sensitivity and specificity for predicting clinician-based Structured Clinical Interview for DSM-IV Axis I Disorders diagnoses of MDD were the primary outcomes. Diagnostic screening accuracy was then compared to that of the Patient Health Questionnaire-9 (PHQ-9). RESULTS: An average of 4 items per participant was required (maximum of 6 items). Overall sensitivity and specificity were 0.95 and 0.87, respectively. For the PHQ-9, sensitivity was 0.70 and specificity was 0.91. CONCLUSIONS: High sensitivity and reasonable specificity for a clinician-based DSM-IV diagnosis of depression can be obtained using an average of 4 adaptively administered self-report items in less than 1 minute. Relative to the currently used PHQ-9, the CAD-MDD dramatically increased sensitivity while maintaining similar specificity. As such, the CAD-MDD will identify more true positives (lower false-negative rate) than the PHQ-9 using half the number of items. Inexpensive (relative to clinical assessment), efficient, and accurate screening of depression in the settings of primary care, psychiatric epidemiology, molecular genetics, and global health are all direct applications of the current system.

Clinical staging in psychiatry: a cross-cutting model of diagnosis with heuristic and practical value.

Staging models are used routinely in general medicine for potentially serious or chronic physical disorders such as diabetes, arthritis and cancers, describing the links between biomarkers, clinical phenotypes and disease extension, and promoting a personalised or stratified medicine approach to treatment planning. Clinical staging involves a detailed description of where an individual exists on a continuum of disorder progression from stage 0 (an at-risk or latency stage) through to stage IV (late or end-stage disease). The approach is popular owing to its clinical utility and is increasingly being applied in psychiatry. The concept offers an informed approach to research and the active promotion of indicated prevention and early intervention strategies. We suggest that for young persons with emerging bipolar disorder, such transdiagnostic staging models could provide a framework that better reflects the developmental psychopathology and matches the complex longitudinal inter-relationships between subsyndromal and syndromal mood, psychotic and other disorders.

Development of a computerized adaptive test for depression.

CONTEXT Unlike other areas of medicine, psychiatry is almost entirely dependent on patient report to assess the presence and severity of disease; therefore, it is particularly crucial that we find both more accurate and efficient means of obtaining that report. OBJECTIVE To develop a computerized adaptive test (CAT) for depression, called the Computerized Adaptive Test-Depression Inventory (CAT-DI), that decreases patient and clinician burden and increases measurement precision. DESIGN Case-control study. SETTING A psychiatric clinic and community mental health center. PARTICIPANTS A total of 1614 individuals with and without minor and major depression were recruited for study. MAIN OUTCOME MEASURES The focus of this study was the development of the CAT-DI. The 24-item Hamilton Rating Scale for Depression, Patient Health Questionnaire 9, and the Center for Epidemiologic Studies Depression Scale were used to study the convergent validity of the new measure, and the Structured Clinical Interview for DSM-IV was used to obtain diagnostic classifications of minor and major depressive disorder. RESULTS A mean of 12 items per study participant was required to achieve a 0.3 SE in the depression severity estimate and maintain a correlation of r = 0.95 with the total 389-item test score. Using empirically derived thresholds based on a mixture of normal distributions, we found a sensitivity of 0.92 and a specificity of 0.88 for the classification of major depressive disorder in a sample consisting of depressed patients and healthy controls. Correlations on the order of r = 0.8 were found with the other clinician and self-rating scale scores. The CAT-DI provided excellent discrimination throughout the entire depressive severity continuum (minor and major depression), whereas the traditional scales did so primarily at the extremes (eg, major depression). CONCLUSIONS Traditional measurement fixes the number of items administered and allows measurement uncertainty to vary. In contrast, a CAT fixes measurement uncertainty and allows the number of items to vary. The result is a significant reduction in the number of items needed to measure depression and increased precision of measurement.

An adaptation of the Interpersonal Problem Areas Rating Scale: pilot and interrater agreement study / Adaptação da Escala de Áreas Problema da Psicoterapia Interpessoal: estudo piloto e avaliação de concordância

OBJECTIVE: This article describes the adaptation of a rating scale of interpersonal psychotherapy problem areas to include a fifth problem area appropriate to bipolar disorder and an interrater agreement study in identifying interpersonal problem areas and selecting a primary treatment focus if patients were to engage in treatment. METHOD: Five research interpersonal psychotherapists assessed nine audiotapes of a single interview with five bipolar and four unipolar patients in which the interpersonal inventory and identification of problem areas were undertaken. RESULTS: Raters agreed on presence and absence of problem areas in seven tapes. Kappas for identification of problem areas were 1.00 (grief), 0.77 (role dispute), 0.61 (role transition), 0.57 (interpersonal deficits) and 1.00 (loss of healthy self). Kappa for agreement on a primary clinical focus if patients were to engage in interpersonal psychotherapy treatment was 0.64. CONCLUSIONS: The adaptation of the original scale to include an area pertinent to bipolar disorder proved to be applicable and relevant for use with this population. The results show substantial interrater agreement in identifying problem areas and potential treatment focus.

OBJETIVO: Este artigo descreve a adaptação de uma escala de avaliação de áreas problema da psicoterapia interpessoal que inclui uma área própria ao transtorno bipolar e um estudo de concordância em identificar áreas problema e selecionar um foco primário de tratamento caso os pacientes fossem participar de tratamento. MÉTODO: Cinco terapeutas interpessoais avaliaram nove audiotapes de uma única entrevista com cinco pacientes bipolares e quatro pacientes unipolares em que o inventário interpessoal e identificação de áreas problema foram empreendidos. RESULTADOS: Os avaliadores concordaram na presença e ausência de áreas problema em sete fitas. Kappas para identificação de áreas problema foram 1,00 (luto), 0,77 (disputa de papel), 0,61 (transição de papel), 0,57 (déficits interpessoais) e 1,00 (perda do self sadio). Kappa para concordância num foco de tratamento clínico foi 0,64. CONCLUSÕES: A adaptação da escala original para incluir área pertinente ao transtorno bipolar mostrou-se relevante para o uso com tal população. Os resultados demonstram uma concordância substancial entre avaliadores na identificação de áreas problema e foco de tratamento.

Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group Report.

OBJECTIVE: The National Heart, Lung, and Blood Institute convened an interdisciplinary working group of experts to develop recommendations for the assessment and treatment of depression in patients with coronary heart disease (CHD). METHOD: Consensus of experts. RESULTS: Our current recommendations are that the Beck Depression Inventory-I be employed for epidemiological studies of depression and CHD, that the Patient Health Questionnaire 2-item version be employed for screening for trial eligibility, that the Depression Interview and Structured Hamilton (DISH) be employed for diagnostic ascertainment for trial inclusion, and that the Hamilton rating scale, which is part of the DISH, be employed for both depression symptom reduction and the remission criterion in any trial. We further recommend that a randomized controlled trial be undertaken to determine whether selective serotonin reuptake inhibitors, psychotherapy, or combined treatment can reduce the risk of CHD events and mortality associated with depression in CHD patients. CONCLUSIONS: This report summarizes the recommendations made by the working group and discusses the rationale for each recommendation, the strengths and weaknesses of alternative approaches to assessment and treatment, and the implications for future research in this area.

Cross-cultural validity of the structured clinical interview for panic-agoraphobic spectrum.

BACKGROUND: We sought to develop a series of assessment measures of psychiatric spectrum conditions associated with major DSM-IV mood and anxiety disorders that might capture the true phenotypes underlying these disorders. The specific objective of this report was to describe the methods we employed to create instruments that could cross linguistic and national boundaries and to evaluate the comparability of results obtained when one of these instruments, the Structured Clinical Interview for Panic-Agoraphobic Spectrum (SCI-PAS), was administered in the United States and in Italy. METHOD: After developing, in parallel, the English and the Italian versions of the SCI-PAS, identical protocols were conducted in patients and control samples at the University of Pittsburgh and the University of Pisa to examine the reliability and validity of the interview. RESULTS: Total and domain scores on the SCI-PAS were strikingly similar in the US and Italian patient groups and in controls. In addition, similarly high levels of inter-rater and test-retest reliability were found at the two sites. Finally, virtually identical patterns of relationships were found between the domains of the SCI-PAS and established measures of the same constructs. CONCLUSIONS: The SCI-PAS displays similar reliability and validity properties in the two versions. This suggests that the instrument taps a phenotype that is consistent in American and Italian patient and control populations.

Acute treatment outcomes in patients with bipolar I disorder and co-morbid borderline personality disorder receiving medication and psychotherapy.

OBJECTIVE: Patients suffering from both bipolar I disorder and borderline personality disorder (BPD) pose unique treatment challenges. The purpose of this matched case-control study was to compare acute treatment outcomes of a sample of patients who met standardized diagnostic criteria for both bipolar I disorder and BPD (n = 12) to those who met criteria for bipolar I disorder only (n = 58). METHOD: Subjects meeting criteria for an acute affective episode were treated with a combination of algorithm-driven pharmacotherapy and weekly psychotherapy until stabilization (defined as four consecutive weeks with a calculated average of the 17-item version of the Hamilton Rating Scale for Depression and Bech-Rafaelsen Mania scale totaling < or = 7). RESULTS: Only three of 12 (25%) bipolar-BPD patients achieved stabilization, compared with 43 of 58 (74%) bipolar-only patients. Two of the three bipolar-BPD patients who did stabilize took over 95 weeks to do so, compared with a median time-to-stabilization of 35 weeks in the bipolar-only group. The bipolar-BPD group received significantly more atypical mood-stabilizing medications per year than the bipolar-only group (Z = 4.3, p < 0.0001). Dropout rates in the comorbid group were high. CONCLUSIONS: This quasi-experimental study suggests that treatment course may be longer in patients suffering from both bipolar I disorder and BPD. Some patients improved substantially with pharmacotherapy and psychotherapy, suggesting that this approach is worthy of further investigation.

Computerized adaptive measurement of depression: a simulation study.

BACKGROUND: Efficient, accurate instruments for measuring depression are increasingly important in clinical practice. We developed a computerized adaptive version of the Beck Depression Inventory (BDI). We examined its efficiency and its usefulness in identifying Major Depressive Episodes (MDE) and in measuring depression severity. METHODS: Subjects were 744 participants in research studies in which each subject completed both the BDI and the SCID. In addition, 285 patients completed the Hamilton Depression Rating Scale. RESULTS: The adaptive BDI had an AUC as an indicator of a SCID diagnosis of MDE of 88%, equivalent to the full BDI. The adaptive BDI asked fewer questions than the full BDI (5.6 versus 21 items). The adaptive latent depression score correlated r =.92 with the BDI total score and the latent depression score correlated more highly with the Hamilton (r =.74) than the BDI total score did (r =.70). CONCLUSIONS: Adaptive testing for depression may provide greatly increased efficiency without loss of accuracy in identifying MDE or in measuring depression severity.

2001 anthrax crisis in Washington, D.C.: pharmacists' role in screening patients and selecting prophylaxis.

Pharmacists' development and use of a worksheet facilitating their rapid selection of patient-appropriate prophylactic antimicrobials in an anthrax clinic is described. A clinic housed at D.C. General Hospital, in Washington, D.C., treated most of the people--many of them postal workers--who may have been exposed to anthrax in that city during the 2001 anthrax crisis. A form was needed to assist pharmacists in the rapid selection of prophylactic antimicrobials and in patient education and counseling. A team of pharmacists collaborated on the development of a form tailored to the clinical and logistical needs of the operation. The questions on the form were based largely on the two antianthrax agents most likely to be used, ciprofloxacin and doxycycline, and were designed to identify the circumstances that would most frequently require a medication change or a modification of patient education. Yes-or-no check boxes allowed pertinent data to be captured most efficiently. A positive response to any question triggered a personal interview and assessment by a pharmacist. A treatment algorithm was also developed to ensure consistent pharmacist selection of agents in the face of potentially changing policies and staff. The worksheet questions sought to establish treatment objectives, document allergies and concomitant therapies, and identify patients who were pregnant or lactating. Pharmacists developed a patient-screening worksheet that helped determine their choice of treatment for people who may have been exposed to anthrax in Washington, D.C., during the 2001 anthrax crisis.

Demographic and clinical characteristics of individuals in a bipolar disorder case registry.

BACKGROUND: The goal of this analysis was to characterize a cohort of 3000 persons who self-identified as having bipolar disorder by demographic, clinical, and treatment characteristics and to document the burden that this disorder imposed on their lives. METHOD: The Stanley Center Bipolar Disorder Registry used a variety of recruitment methods to reach people with bipolar disorder. The cohort included those currently in treatment and those active in support groups. Registrants completed an interviewer-administered questionnaire to obtain information on demographic characteristics, clinical history, and treatment history. RESULTS: The median age of the 2839 patients who were analyzed was 40.1 years, 64.5% were women, and over 90% were white. The median age at onset was 17.5 years, and the mean was 19.8 years. Despite the fact that over 60% completed at least some college and 30% completed college, 64% were currently unemployed. The patients' family histories point to a high prevalence of mental disorder in the families, especially mood disorders. Patients were concurrently taking multiple medications, and more than one third were taking at least 3 types of psychotropic medications. This pattern of pharmacotherapy was consistent with participants' overall mood ratings, which demonstrated how unusual it was for them to be symptom-free over a 6-month period. CONCLUSION: Our present findings point to the chronicity and severity of bipolar disorder as experienced in the community. We still need to develop better interventions, ensure access to care consistent with current consensus guidelines, and initiate care as early as possible in the course of the condition.