Publications by authors named "David Kupfer"

The nature of data obtainable from the commercial smartphone - bolstered by a translational model emphasizing the impact of social and physical zeitgebers on circadian rhythms and mood - offers the possibility of scalable and objective vital signs for major depression. Our objective was to explore associations between passively sensed behavioral smartphone data and repeatedly measured depressive symptoms to suggest which features could eventually lead towards vital signs for depression. We collected continuous behavioral data and bi-weekly depressive symptoms (PHQ-8) from 131 psychiatric outpatients with a lifetime DSM-5 diagnosis of depression and/or anxiety over a 16-week period.

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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.

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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;  = 28).

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In clinical practice, differentiating Bipolar Disorder (BD) from unipolar depression is a challenge due to the depressive symptoms, which are the core presentations of both disorders. This misdiagnosis during depressive episodes results in a delay in proper treatment and a poor management of their condition. In a first step, using A-to-I RNA editome analysis, we discovered 646 variants (366 genes) differentially edited between depressed patients and healthy volunteers in a discovery cohort of 57 participants.

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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.

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We thank Kaufman et al. 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.

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Sleep disturbances, including insomnia (difficulty falling or staying asleep), are common nicotine withdrawal symptoms particularly during the initial stage of nicotine abstinence, and increase the likelihood of relapse within the first 4 weeks of quitting. Although clinically recognized as a key symptom of nicotine withdrawal, sleep disturbances are not addressed in the clinical guidelines for nicotine dependence treatment. Unfortunately, Nicotine Replacement Therapy (NRT) and other pharmacologic interventions do not attenuate withdrawal-provoked sleep disturbances, with several even exacerbating sleep disruption.

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Exercise is presumed to be a potentially helpful smoking cessation adjunct reputed to attenuate the negative effects of deprivation. The present study examined the effectiveness of moderate within-session exercise to reduce 4 key symptoms of smoking deprivation during 3 72-hr nicotine abstinence blocks in both male and female smokers. Forty-nine (25 male, 24 female) sedentary smokers abstained from smoking for 3 consecutive days on 3 separate occasions.

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Importance: Early identification of individuals at high risk for the onset of bipolar spectrum disorder (BPSD) is key from both a clinical and research perspective. While previous work has identified the presence of a bipolar prodrome, the predictive implications for the individual have not been assessed, to date.

Objective: To build a risk calculator to predict the 5-year onset of BPSD in youth at familial risk for BPSD.

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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.

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Background: Sleep disturbances are a prominent feature of bipolar disorder (BP). However, it remains unclear how sleep phenotypes may evolve among at-risk youth, and their relevance to BP onset.

Methods: Pittsburgh Bipolar Offspring Study (BIOS) offspring (ages 10-18) and their parents completed assessments approximately every two years pertaining to current psychopathology and offspring sleep habits.

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Background: Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Schedule (SLES) among 3 groups of adolescent offspring of probands with bipolar (BD), with non-BD psychiatric disorders, and healthy controls. Furthermore, we examined the relationship between stressful life events and the presence of DSM-IV Axis I disorders in these offspring.

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Background: The diagnostic scheme for psychiatric disorders is currently based purely on descriptive nomenclature given that biomarkers subtypes and clearly defined causal mechanisms are lacking for the vast majority of disorders. The emerging field of "immuno-psychiatry" has the potential to widen the exploration of a mechanism-based nosology, possibly leading to the discovery of more effective personalised treatment strategies.

Discussion: Disturbances in immuno-inflammatory and related systems have been implicated in the aetiology, pathophysiology, phenomenology and comorbidity of several psychiatric disorders, including major mood disorders and schizophrenia.

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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.

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Study Objectives: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMR) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS).

Methods: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21-60), sex, and race.

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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.

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Objective: The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths).

Method: Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.

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