Eric A Nofzinger

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (74)455.7 Total impact

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    ABSTRACT: Rapid eye movement (REM) sleep disturbances predict poor clinical outcomes in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In MDD, REM sleep is characterized by activation of limbic and paralimbic brain regions compared to wakefulness. The neural correlates of PTSD during REM sleep remain scarcely explored, and comparisons of PTSD and MDD have not been conducted. The present study sought to compare brain activity patterns during wakefulness and REM sleep in 13 adults with PTSD and 12 adults with MDD using [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET). PTSD was associated with greater increase in relative regional cerebral metabolic rate of glucose (rCMRglc) in limbic and paralimbic structures in REM sleep compared to wakefulness. Post-hoc comparisons indicated that MDD was associated with greater limbic and paralimbic rCMRglc during wakefulness but not REM sleep compared to PTSD. Our findings suggest that PTSD is associated with increased REM sleep limbic and paralimbic metabolism, whereas MDD is associated with wake and REM hypermetabolism in these areas. These observations suggest that PTSD and MDD disrupt REM sleep through different neurobiological processes. Optimal sleep treatments between the two disorders may differ: REM-specific therapy may be more effective in PTSD.
    Psychiatry Research Neuroimaging 01/2013; 214(3):422–428. · 3.36 Impact Factor
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    ABSTRACT: Relative regional cerebral metabolic rate of glucose in rapid eye movement (REM) sleep and wakefulness was explored in combat veterans with and without PTSD, using positron emission tomography. Hypermetabolism in brain regions involved in arousal regulation, fear responses, and reward processing persist during REM sleep in combat veterans with PTSD.
    Psychiatry research. 11/2012;
  • Journal of psychosomatic research 08/2012; 73(2):154-5. · 2.91 Impact Factor
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    ABSTRACT: While insomnia is a well-established risk factor for the initial onset, recurrence or relapse of affective disorders, the specific characteristics of insomnia that confer risk remain unclear. Patients with insomnia with an evening chronotype may be one particularly high-risk group, perhaps due to alterations in positive affect and its related affective circuitry. We explored this possibility by comparing diurnal patterns of positive affect and the activity of positive affect-related brain regions in morning- and evening-types with insomnia. We assessed diurnal variation in brain activity via the relative regional cerebral metabolic rate of glucose uptake by using [(18) F]fluorodeoxyglucose-positron emission tomography during morning and evening wakefulness. We focused on regions in the medial prefrontal cortex and striatum, which have been consistently linked with positive affect and reward processing. As predicted, chronotypes differed in their daily patterns in both self-reported positive affect and associated brain regions. Evening-types displayed diurnal patterns of positive affect characterized by phase delay and smaller amplitude compared with those of morning-types with insomnia. In parallel, evening-types showed a reduced degree of diurnal variation in the metabolism of both the medial prefrontal cortex and the striatum, as well as lower overall metabolism in these regions across both morning and evening wakefulness. Taken together, these preliminary findings suggest that alterations in the diurnal activity of positive affect-related neural structures may underlie differences in the phase and amplitude of self-reported positive affect between morning and evening chronotypes, and may constitute one mechanism for increased risk of mood disorders among evening-type insomniacs.
    Journal of Sleep Research 02/2012; 21(5):515-26. · 3.04 Impact Factor
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    ABSTRACT: Pharmacological and cognitive-behavioral treatments targeting insomnia and nightmares have been shown to be effective in the treatment of military veterans with sleep complaints comorbid with symptoms of stress-related disorders, including Post-Traumatic Stress Disorder (PTSD), but the two approaches have not been directly compared. This randomized controlled trial compared the effects of prazosin vs. a behavioral sleep intervention (BSI), targeting nightmares and insomnia against a placebo pill control condition on sleep and daytime symptoms. Fifty United States military veterans (mean age 40.9years, SD=13.2years) with chronic sleep disturbances were randomized to prazosin (n=18), BSI (n=17), or placebo (n=15). Each intervention lasted 8weeks. Participants completed self-report measures of insomnia severity, sleep quality, and sleep disturbances. All kept a sleep diary throughout the intervention period. Polysomnographic studies were conducted pre- and post-intervention. Both active treatment groups showed greater reductions in insomnia severity and daytime PTSD symptom severity. Sleep improvements were found in 61.9% of those who completed the active treatments and 25% of those randomized to placebo. BSI and prazosin were both associated with significant sleep improvements and reductions in daytime PTSD symptoms in this sample of military veterans. Sleep-focused treatments may enhance the benefits of first-line PTSD treatments.
    Journal of psychosomatic research 02/2012; 72(2):89-96. · 2.91 Impact Factor
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    ABSTRACT: Insomnia is a common clinical condition resulting in significant costs and morbidity. Previous models of insomnia focusing on psychological and behavioral processes are useful clinically, but lack neurobiological specificity. We propose an insomnia model based on basic and clinical neuroscience findings, and hypothesize that insomnia results from persistent activity in wake-promoting neural structures during NREM sleep. The simultaneous occurrence of sleeping and waking neural activity helps to explain clinical phenomenology and treatment effects in insomnia.
    Drug Discovery Today Disease Models 01/2011; 8(4):129-137.
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    Anne Germain, Eric A. Nofzinger
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    ABSTRACT: This is the final report for this study. We have completed all pre-and post assessment in all participants randomized to prazosin, placebo, or the behavioral sleep intervention. Two participants are currently completing the 4-month follow-up period. Data analysis for the acute treatment phase is currently underway, and the final analyses (which include 4-month follow-up data) will be initiated shortly. Recruitment has been more difficult than anticipated, but our enrollment rate (10% of individuals who completed the initial screening) is consistent with other ongoing studies in this population. Over the course of the performance period to date, this award has produced a number of reportable outcomes, including several scientific, peer-review presentations and symposia, and provided preliminary data for three successful applications for federal funding by the PI, Dr. Germain.
    02/2010;
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    ABSTRACT: The aim of this study was to investigate the effects of obstructive sleep apnea (OSA) on procedural and declarative memory encoding in the evening prior to sleep, on memory consolidation during subsequent sleep, and on retrieval in the morning after sleep. Memory performance (procedural mirror-tracing task, declarative visual and verbal memory task) and general neuropsychological performance were assessed before and after one night of polysomnographic monitoring in 15 patients with moderate OSA and 20 age-, sex-, and IQ-matched healthy subjects. Encoding levels prior to sleep were similar across groups for all tasks. Conventional analyses of averaged mirror tracing performance suggested a significantly reduced overnight improvement in OSA patients. Single trial analyses, however, revealed that this effect was due to significantly flattened learning curves in the evening and morning session in OSA patients. OSA patients showed a significantly lower verbal retention rate and a non-significantly reduced visual retention rate after sleep compared to healthy subjects. Polysomnography revealed a significantly reduced REM density, increased frequency of micro-arousals, elevated apnea-hypopnea index, and subjectively disturbed sleep quality in OSA patients compared to healthy subjects. The results suggest that moderate OSA is associated with a significant impairment of procedural and verbal declarative memory. Future work is needed to further determine the contribution of structural or functional alterations in brain circuits relevant for memory, and to test whether OSA treatment improves or normalizes the observed deficits in learning.
    Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 12/2009; 5(6):540-8. · 2.93 Impact Factor
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    ABSTRACT: To determine in healthy people aged > or = 75 years 1) if restricting time in bed and education in health sleep practices are superior to an attention-only control condition (i.e., education in healthy dietary practices) for maintaining or enhancing sleep continuity and depth over 2.5 years; and 2) if maintenance or enhancement of sleep continuity and depth promotes the maintenance or enhancement of health-related quality of life. Single-blind, randomized, clinical trial in a university-based sleep center, enrolling 64 adults (n = 30 women, 34 men; mean age = 79 years) without sleep/wake complaints (e.g., insomnia or daytime sleepiness), followed by randomized assignment to either: 1) restriction of time in bed by delaying bedtime 30 minutes nightly for 18 months, together with education in healthy sleep practices (SLEEP); or 2) attention-only control condition with education in health dietary practices (NUTRITION). SLEEP did not enhance sleep continuity or depth; however, compared with NUTRITION, SLEEP was associated with decreased time spent asleep (about 30 minutes nightly over 18 months). Contrary to hypothesis, participants in SLEEP reported a decrement in physical health-related quality of life and an increase in medical burden (cardiovascular illness), relative to NUTRITION. Neither markers of inflammation, body mass index, or exercise explained treatment-related changes in medical burden. Although we cannot exclude a positive effect of education in healthy nutrition, for healthy elderly >75 years of age without sleep complaints, reducing sleep time may be detrimental, whereas allowing more time to sleep (about 7.5 hours nightly) is associated with better maintenance of physical health-related quality of life and stability of medical illness burden over 30 months.
    Psychosomatic Medicine 12/2009; 72(2):178-86. · 4.08 Impact Factor
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    ABSTRACT: To compare NREM EEG power in primary insomnia (PI) and good sleeper controls (GSC), examining both sex and NREM period effects; to examine relationships between EEG power, clinical characteristics, and self-reports of sleep. Overnight polysomnographic study. Sleep laboratory. PI (n=48; 29 women) and GSC (n=25; 15 women). None. EEG power from 1-50 Hz was computed for artifact-free sleep epochs across four NREM periods. Repeated measures mixed effect models contrasted differences between groups, EEG frequency bands, and NREM periods. EEG power-frequency curves were modeled using regressions with fixed knot splines. Mixed models showed no significant group (PI vs. GSC) differences; marginal sex differences (delta and theta bands); significant differences across NREM periods; and group*sex and group*NREM period interactions, particularly in beta and gamma bands. Modeled power-frequency curves showed no group difference in whole-night NREM, but PI had higher power than GSC from 18-40 Hz in the first NREM period. Among women, PI had higher 16 to 44-Hz power than GSC in the first 3 NREM periods, and higher 3 to 5-Hz power across all NREM periods. PI and GSC men showed no consistent differences in EEG power. High-frequency EEG power was not related to clinical or subjective sleep ratings in PI. Women with PI, but not men, showed increased high-frequency and low-frequency EEG activity during NREM sleep compared to GSC, particularly in early NREM periods. Sex and NREM period may moderate quantitative EEG differences between PI and GSC.
    Sleep 01/2009; 31(12):1673-82. · 5.10 Impact Factor
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    Anne Germain, Daniel J Buysse, Eric Nofzinger
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is a prevalent disorder that is associated with poor clinical and health outcomes, and considerable health care utilization and costs. Recent estimates suggest that 5-20% of military personnel who serve in current conflicts in Iraq and Afghanistan meet diagnostic criteria for PTSD. Clinically, sleep disturbances are core features of PTSD that are often resistant to first-line treatments, independently contribute to poor daytime functioning, and often require sleep-focused treatments. Physiologically, these observations suggest that PTSD is partially mediated by sleep disruption and its neurobiological correlates that are not adequately addressed by first-line treatments. However, polysomnographic studies have provided limited insights into the neurobiological underpinnings of PTSD during sleep. There is an urgent need to apply state-of-the-science sleep measurement methods to bridge the apparent gap between the clinical significance of sleep disturbances in PTSD and the limited understanding of their neurobiological underpinnings. Here, we propose an integrative review of findings derived from neurobiological models of fear conditioning and fear extinction, PTSD, and sleep-wake regulation, suggesting that the amygdala and medial prefrontal cortex can directly contribute to sleep disturbances in PTSD. Testable hypotheses regarding the neurobiological underpinnings of PTSD across the sleep-wake cycle are offered.
    Sleep Medicine Reviews 07/2008; 12(3):185-95. · 8.68 Impact Factor
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    ABSTRACT: To examine diary-based, laboratory-based, and actigraphic measures of sleep in a group of healthy older women and men (> or =75 years of age) without sleep/wake complaints and to describe sleep characteristics which may be correlates of health-related quality of life in old age. Cross-sectional, descriptive study. University-based sleep and chronobiology program. None. Sixty-four older adults (30 women, 34 men; mean age 79). We used diary-, actigraphic-, and laboratory-based measures of sleep, health-related quality of life, mental health, social support, and coping strategies. We used two-group t-tests to compare baseline demographic and clinical measures between men and women, followed by ANOVA on selected EEG measures to examine first-night effects as evidence of physiological adaptability. Finally, we examined correlations between measure of sleep and health-related quality of life. We observed that healthy men and women aged 75 and older can experience satisfactory nocturnal sleep quality and daytime alertness, especially as reflected in self-report and diary-based measures. Polysomnography (psg) suggested the presence of a first-night effect, especially in men, consistent with continued normal adaptability in this cohort of healthy older adults. Continuity and depth of sleep in older women were superior to that of men. Diary-based measures of sleep quality (but not psg measures) correlated positively (small to moderate effect sizes) with physical and mental health-related quality of life. Sleep quality and daytime alertness in late life may be more important aspects of successful aging than previously appreciated. Good sleep may be a marker of good functioning across a variety of domains in old age. Our observations suggest the need to study interventions which protect sleep quality in older adults to determine if doing so fosters continued successful aging.
    American Journal of Geriatric Psychiatry 02/2008; 16(1):74-82. · 4.13 Impact Factor
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    ABSTRACT: Although psychological stress has been associated with disturbed sleep in younger populations, little is known about the stress-sleep relationship in late-life. In the present study, we evaluated relationships among a chronic stressor, ongoing financial strain, and sleep in a heterogenous sample (n=75) of community-dwelling elders (mean age=74.0 years). Self-report measures included ongoing financial strain, mental health, physical health and subjective sleep quality. Sleep duration, continuity, and architecture were measured by polysomnography (PSG). Analysis of variance and regression were used to test the hypothesis that ongoing financial strain is a significant correlate of disturbed sleep in the elderly. Covariates included age, sex, mental health and physical health. Analyses revealed that ongoing financial strain is a significant correlate of PSG-assessed sleep latency, wakefulness after sleep onset, and sleep efficiency. After adjusting for the effects of age, sex, mental health, and physical health on sleep, ongoing financial strain was associated with lower sleep efficiency (p<.01). Our results show that chronic stress, as measured by ongoing financial strain, is a significant correlate of sleep disturbances in the elderly, even after adjusting for factors known to impact sleep in late-life.
    Biological Psychology 02/2008; 77(2):217-22. · 3.40 Impact Factor
  • Eric A Nofzinger
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    ABSTRACT: Functional neuroimaging methods provide a means to understand brain function in patients with sleep disorders. This paper summarizes functional neuroimaging findings in sleep disorders patients, and studies addressing the pharmacology of sleep and sleep disorders. Areas in which functional neuroimaging methods may be helpful in sleep medicine, and in which future development is advised, include: 1) clarification of pathophysiology; 2) aid in differential diagnosis; 3) assessment of treatment response; 4) guiding new drug development; and 5) monitoring treatment response.
    Current pharmaceutical design 02/2008; 14(32):3417-29. · 4.41 Impact Factor
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    ABSTRACT: This study compared diurnal variation in mood and regional cerebral metabolic rate of glucose (rCMRglc) in depressed and healthy subjects. Depressed and healthy subjects were investigated using [18F]-fluoro-deoxyglucose positron emission tomography scans during morning and evening wakefulness. All subjects completed subjective mood ratings at both times of day. Statistical parametric mapping was used to compare rCMRglc between the two groups across time of day. Depressed patients showed evening mood improvements compared with healthy subjects. Compared with healthy subjects, depressed patients showed smaller increases in rCMRglc during evening relative to morning wakefulness in lingual and fusiform cortices, midbrain reticular formation, and locus coeruleus and greater increases in rCMRglc in parietal and temporal cortices. Depressed patients had hypermetabolism in limbic-paralimbic regions and hypometabolism in frontal and parietal cortex at both times of day compared with healthy subjects. Variation in rCMRglc differs across times of day in depressed and healthy subjects. In depressed patients, evening mood improvements were associated with increased metabolic activity in ventral limbic-paralimbic, parietal, temporal, and frontal regions and in the cerebellum. This increased metabolic pattern during evening wakefulness may reflect partial normalization of primary and compensatory neural systems involved in affect production and regulation.
    Biological Psychiatry 10/2007; 62(5):438-45. · 9.25 Impact Factor
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    ABSTRACT: To prospectively characterize and compare daytime symptoms in primary insomnia (PI) and good sleeper control (GSC) subjects using ecological momentary assessment; to examine relationships between daytime symptom factors, retrospective psychological and sleep reports, and concurrent sleep diary reports. Subjects included 47 PI and 18 GSC. Retrospective self-reports of daytime and sleep symptoms were collected. Daytime symptoms and sleep diary information were then collected for 1 week on hand-held computers. The Daytime Insomnia Symptom Scale (DISS) consisted of 19 visual analog scales completed four times per day. Factors for the DISS were derived using functional principal components analysis. Nonparametric tests were used to contrast DISS, retrospective symptom ratings, and sleep diary results in PI and GSC subjects, and to examine relationships among them. Four principal components were identified for the DISS: Alert Cognition, Negative Mood, Positive Mood, and Sleepiness/Fatigue. PI scored significantly worse than GSC on all four factors (p<0.0003 for each). Among PI subjects DISS scales and retrospective psychological symptoms were related to each other in plausible ways. DISS factors were also related to self-report measures of sleep, whereas retrospective psychological symptom measures were not. Daytime symptom factors of alertness, positive and negative mood, and sleepiness/fatigue, collected with ecological momentary assessment, showed impairment in PI versus GSC. DISS factors showed stronger relationships to retrospective sleep symptoms and concurrent sleep diary reports than retrospective psychological symptoms. The diurnal pattern of symptoms may inform studies of the pathophysiology and treatment outcome of insomnia.
    Sleep Medicine 05/2007; 8(3):198-208. · 3.49 Impact Factor
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    ABSTRACT: Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.
    Journal of Cognitive Neuroscience 12/2006; 18(11):1799-807. · 4.49 Impact Factor
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    ABSTRACT: Laboratory-based sleep studies have yielded inconsistent results regarding the nature of objective sleep anomalies in posttraumatic stress disorder (PTSD). This pilot study aimed at assessing sleep in adult crime victims with PTSD and healthy subjects by using in-home polysomnography. Compared to the control group, PTSD subjects showed longer sleep latency and reduced total sleep time. Ambulatory methods can capture objective signs of sleep disruption and corroborate subjective complaints of disrupted sleep in PTSD.
    Sleep and Biological Rhythms 09/2006; 4(3):286 - 289. · 1.05 Impact Factor
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    ABSTRACT: To compare sleep-related consolidation of procedural memory in patients with primary insomnia and healthy controls. Controlled comparison pilot study. Sleep Laboratory of the Department of Psychiatry and Psychotherapy, University of Freiburg, Germany. Seven patients with primary insomnia and 7 sex-, age-, and IQ-matched healthy controls. Subjects spent 1 night in the sleep laboratory with polysomnographic monitoring. Performance on a mirror tracing task was measured before and after sleep. Polysomnography revealed a trend toward disturbed sleep in the patients, compared with the control group, without reaching significance. Performance in the mirror tracing task before sleep did not differ between the groups. Both groups performed significantly better in the retest condition after sleep. Healthy controls showed an improvement of 42.8% +/- 5.8% in the mirror tracing draw time, whereas patients with insomnia showed an improvement of 20.4% +/- 14.8% (multivariate analyses of variance test session x group interaction: F(3,10) = 10.9, p = .002). These preliminary findings support the view that sleep-associated consolidation of procedural memories may be impaired in patients with primary insomnia.
    Sleep 09/2006; 29(8):1068-73. · 5.10 Impact Factor
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    ABSTRACT: The aim of this study was to determine whether naturally occurring inter-individual and intra-individual differences in bedtime selection in the elderly might be lawfully related to the amount of sleep that is obtained. A total of 128 seniors (63f, 65m) aged 70–92 years each provided a week of sleep diary data yielding a total of 896 subject-nights for analysis. From each subject-night the diary was used to derive measures of time in bed (TIB) and total sleep time (TST). These measures were used as dependent variables in mixed-effect linear models (nights nested within subjects) with the independent variable being bedtime for that subject-night, arbitrarily expressed as minutes since 19:00 hours. Although there were strong inter-individual and intra-individual differences, for both genders, bedtime had a statistically significant effect (P < 0.001) on both TIB and TST. We observed that later bedtimes were associated with less time in bed and less time asleep. On average between 7 and 8 min of less TIB and TST were associated with each 10-min delay in bedtime from 19:00 hours. These results are interpreted in terms of increases in sleep being derived from living in a better harmony with an earlier peaking circadian pacemaker characteristic of older age, although other possible mechanisms are also considered (e.g. age-dependent alterations in phase angle and homeostatic sleep need).
    Journal of Sleep Research 08/2006; 15(3):256 - 260. · 3.04 Impact Factor

Publication Stats

2k Citations
455.70 Total Impact Points

Institutions

  • 1993–2013
    • University of Pittsburgh
      • • Department of Psychiatry
      • • School of Medicine
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
  • 2006
    • University of Freiburg
      • Institute of Psychology
      Freiburg, Baden-Württemberg, Germany
  • 1990–2006
    • Western Psychiatric Institute and Clinic
      Pittsburgh, Pennsylvania, United States
  • 1988
    • The Ohio State University
      • Department of Psychiatry
      Columbus, OH, United States