David Kupfer

University of Pittsburgh | Pitt · Department of Psychiatry

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 sm...

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

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...

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...

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 based on social rhythm regulation principles (Cue). The full intent to treat (ITT) sample consisted of 133 individuals, aged 18 to 65. T...

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 editom...

This review focuses on information concerning antidepressants and psychotherapy in the treatement of both acute and chronic forms of unipolar depression in the English language literature. In it, we address the use of combination therapy, both from the outset of treatment and in a variety of sequences, ie, we examine the potential advantages of add...

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...

Introduction In clinical practice, differentiating Bipolar Disorder (BD) from unipolar depression is challenging due to the depressive symptoms, which are the core presentations of both disorders. Patients with BD are often misdiagnosed during depressive episodes resulting in a delay in proper treatment and a poor management of their condition. Ob...

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 a...

Background: At least half of youth 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...

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 (2...

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 calculat...

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...

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 pertaini...

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 health...

Neuropsychopharmacology accepted article preview online, 09 February 2017. doi:10.1038/npp.2017.33.

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...

Delgado-Gomez et al. (2016) have provided an interesting example of the comparison of computerized adaptive testing (CAT) based on unidimensional item response theory (IRT) and a machine learning approach based on decision trees (DT) in the prediction of people who have a history of suicide attempts. ... In the following we attempt to better articu...

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, poss...

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 g...

Study objective: 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 (rCMRglc) in these...

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-repor...

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 forest...

Objective: The goal of this study was to explore the association of timing of and frequency of meals with markers of cardiometabolic risk in patients with bipolar disorder in out-patient maintenance treatment. Methods: We used Pittsburgh Sleep Diary and actigraphy measures for individuals with bipolar I disorder. Linear and logistic regression a...

(Reprinted with permission from The Lancet 2012; 379:1045-55).

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, 8.4% of the...

Electroencephalographic slow-wave activity (0.5–4 Hz) during non-rapid eye movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow wave activity during sleep may promote greater waking prefrontal metabolic rate and, in turn, executive function. However, this process may be affected by a...

Objectives: Disruptions in sleep and dysregulation in circadian functioning may represent core abnormalities in the pathophysiology of bipolar disorder (BP). However, it is not clear whether these dysfunctions are state or trait markers of BP. This report compared sleep and circadian phenotypes among three groups: offspring of parents with BP diag...

Objectives: As outlined in the social zeitgeber hypothesis, social rhythm disrupting (SRD) life events begin a cascade of social and biological rhythm disruption that may lead to the onset of affective episodes in those vulnerable to bipolar disorder. Thus, the study of SRD events is particularly important in individuals with this chronic conditio...

Neuroscience based Nomenclature (NbN) is a new system of classifying psychotropic drugs by their pharmacological profile. The NbN was developed to replace the current indication-based nomenclature and to provide an up-to-date and more useful framework to better inform pharmacological decisions. NbN provides updated relevant and specific scientific,...

The DSM-5 process, and the publication of DSM-5 in 2013, have had a considerable impact on the classification of anxiety disorders. Major changes included the reorganization of the chapter structure, individual groupings of disorders within each chapter from a life span viewpoint, and the use of specifiers. The DSM-5 chapter on anxiety disorders do...

The need for innovative methods to promote training, advancement, and retention of clinical and translational investigators in order to build a pipeline of trainees to focus on mental health-relevant research careers is pressing. The specific aim of the Career Development Institute for Psychiatry is to provide the necessary skill set and support to...

Objectives To study the longitudinal course of sleep timing and circadian preferences in individuals with bipolar disorder (BP) compared to individuals with non-BP psychopathology and healthy controls.Methods Individuals with bipolar I and bipolar II disorder (n = 257), non-BP psychopathology (n = 105), and healthy controls (n = 55) (mean age 40.2...

Objective: Computerized adaptive testing (CAT) provides an alternative to fixed-length assessments. The study validated a suite of computerized adaptive tests for mental health (CAT-MH) in a community psychiatric sample. Methods: A total of 145 adults from a community outpatient clinic, including 19 with no history of a mental disorder (control gr...

Although bipolar disorder is increasingly recognised as a spectrum of multisystem disorders (ie, bipolar disorders), proposed staging models and theories of bipolar disease progression often fail to incorporate longitudinal data or data from multiple domains of dysfunction. We propose that bipolar disorders are best thought of as syndromes, with di...

Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportiv...

Objective: The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder ("high-risk offspring"). Method: High-risk offspring 6-18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudin...

There is growing evidence that bipolar disorder (BD) is associated with inflammation, including abnormal levels of acute-phase C-reactive protein (CRP). Our meta-analysis was conducted to estimate the size of the association between CRP levels and BD, accounting also for subgroup differences (mood phases and treatment). MEDLINE, EMBASE, PsycINFO, a...

Objectives 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.MethodsA total of 122 patie...

Introduction: Chronic medicated patients with schizophrenia have marked reductions in sleep spindle activity and a correlated deficit in sleep-dependent memory consolidation. Using archival data, we investigated whether antipsychotic-naïve early course patients with schizophrenia and young non-psychotic first-degree relatives of patients with schiz...

Objective In this study, we aim to assess whether current mood state (depressed or manic/hypomanic) among parents with a mood disorder affects their reports of their offspring's psychopathology. Method Sixty-five parents with current depression, 42 with current mania/hypomania, 181 with mood disorder in remission, and their offspring (n=479, ages...

Objectives Many of the first-line screening tools for obstructive sleep apnea (OSA) may not be accurate in patients with bipolar disorder due to confounding factors, such as chronic depressive symptoms, weight gain, and sedation due to medications. In the present study, we assessed the feasibility of in-home screening for sleep apnea in patients wi...

The authors describe a model for teaching grant writing and other research survival skills to postdoctoral clinical-research fellows in psychiatry and for improving research mentoring. Over the past 4 years, the authors have developed a course on writing grant applications for postdoctoral clinical-research fellows, using peer-review processes mode...

This review considers evidence that sleep and circadian rhythms are disturbed in bipolar patients during both mood episodes and periods of remission. Indeed, bipolar patients display disturbances of subjective and objective circadian markers, in sleep continuity, and in cortisol and melatonin secretion. Better characterization of sleep and circadia...

Psychiatric disorders have traditionally been classified using a static, categorical approach. However, this approach falls short in facilitating understanding of the development, common comorbid diagnoses, prognosis and treatment of these disorders. We propose a 'staging' model of bipolar disorder that integrates genetic and neural information wit...

Objective: Pediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive nondirective therapy (SNDT) in treating youth with comorbid IBD and depression. Method: Youth (51% female and 49% male; age 9-17 years, mean age 14.3 years) with d...

Background / Purpose: Previous research has shown that chronic medicated patients with schizophrenia have a dramatic reduction in sleep spindle activity that correlates with deficient sleep dependent memory consolidation. Archival data was used to investigate whether antipsychotic-naïve early course patients with schizophrenia also show reduced s...

Background / Purpose: Previous research has shown that chronic medicated patients with schizophrenia have a dramatic reduction in sleep spindle activity that correlates with deficient sleep dependent memory consolidation. Archival data was used to investigate whether young non-psychotic first-degree relatives of schizophrenia patients also showed...

We appreciate Dr. Kawada’s interest in our paper1 and the opportunity to respond. Our manuscript presented secondary analyses and should be considered exploratory. Dr. Kawada notes the small number of controls. We agree and included this as a limitation in our original publication. Given the high subject burden of this study, it was difficult to re...

The development of the DSM-5 over the past decade included a systematic review of the major scientific and methodological advances made in the last two decades. The organizational chapter structure for the DSM has been reorganized to facilitate both clinical practice and teaching to improve assessment skills and at the same time, appreciate how to...

The declining success rate of National Institutes of Health (NIH) grant applications highlights the need for interdisciplinary work within a large, diverse department to improve chances of federal funding success. The authors demonstrate how systematic peer review promotes two goals: enhancing the quality of research proposals and cultivating a col...

Bipolar disorder (BP) has been associated with increased aggressive behaviors. However, all existing studies are cross-sectional and include forensic or inpatient populations and many do not take into account the effects of comorbid conditions. The goal of this study was to evaluate the longitudinal course of aggression among adult outpatients with...

The association between Inflammatory bowel disease (IBD) and depression provides a unique opportunity to understand the relationship between systemic inflammation and depressive symptom profiles. Youth (n = 226) ages 9-17 years with co-morbid IBD and depression underwent psychiatric assessment and evaluation of IBD activity. Latent profile analysis...

To the Editor We apologize to the editors and readers of JAMA Psychiatry for our failure to fully disclose our financial interests in an article1 that reported a diagnostic tool, the Computerized Adaptive Test for Depression (CAT-DI). Following acceptance of the paper, we disclosed that “The CAT-DI will ultimately be made available for routine admi...

To explore which symptoms are common in patients who experience a range of symptom severity that spans minor depression and major depressive disorder (MDD). A post hoc analysis of subjects entering outpatient, pharmacologic treatment studies for minor depression or MDD who provided baseline data on the Inventory for Depressive Symptomatology-Clinic...

Current psychopharmacological nomenclature remains wedded in an earlier period of scientific understanding, failing to reflect contemporary developments and knowledge, does not aid clinicians in selecting the best medication for a given patient, and tends to confuse patients by prescribing a drug that does not reflect their identified diagnosis (e....

In this podcast we talk to Prof David Kupfer about the challenges, controversies and future directions of DSM-5 by considering other research frameworks and classification systems of disease, and how this revised psychiatric diagnostic manual will impact global mental health classification and the field of medicine. The podcast for this interview i...

Differentiating bipolar from recurrent unipolar depression is a major clinical challenge. In 18 healthy females and 36 females in a depressive episode – 18 with bipolar disorder type I, 18 with recurrent unipolar depression – we applied pattern recognition analysis using subdivisions of anterior cingulate cortex (ACC) blood flow at rest, measured w...

Objective: The authors developed a computerized adaptive test for anxiety that decreases patient and clinician burden and increases measurement precision. Method: A total of 1,614 individuals with and without generalized anxiety disorder from a psychiatric clinic and community mental health center were recruited. The focus of the present study w...

Objective: This article describes the clinical utility and feasibility of proposed DSM-5 criteria and measures as tested in the DSM-5 Field Trials in Routine Clinical Practice Settings (RCP). METHODS RCP data were collected online for six months (October 2011 to March 2012). Participants included psychiatrists, licensed clinical psychologists, cli...