Cocaine Dependence: EEG Sleep and Cytokines

Summary

Principal Investigator: M Irwin
Affiliation: University of California
Country: USA
Abstract: Sleep disturbance is a prominent complaint of cocaine dependent patients during usage, and also following withdrawal and abstinence. However, the high frequency of disordered sleep stands in sharp contrast with limited effort to fully evaluate sleep or to identify the mechanisms that account for sleep abnormalities associated with chronic cocaine abuse. Given evidence that cocaine addiction also leads to a striking increase in the risk of infectious disease, we hypothesize that the complex cytokine network is one physiological system that mediates both sleep and immune abnormalities in cocaine dependence. Basic observations demonstrate that cytokines play a key role in the regulation of sleep. Translation of cytokine-sleep mechanisms into the clinic show that sleep loss and disturbances of sleep architecture are coincident with alterations in pro-inflammatory and helper T cell type 1/type 2 (Th1/Th2) cytokines, and that cytokine abnormalities predict disordered sleep in cocaine dependent patients. Thus, the over-arching objective of this study is to evaluate sleep and the reciprocal relationships between sleep and cytokine expression in cocaine dependent patients during acute and protracted abstinence as compared to controls. Acute administration of cocaine will serve as a pharmacologic probe of cytokine-sleep regulatory processes. The specific aims of this study are to: 1) evaluate whether cocaine and cocaine dependence are associated with disturbances of sleep including loss of delta sleep and increases of REM sleep; 2) determine the predictive validity of proteomic measures of nocturnal pro-inflammatory-, Th1, and Th2 cytokines on sleep depth in cocaine dependent subjects during acute- and protracted abstinence and following acute cocaine administration; 3) examine the consequences of disordered sleep on the expression of pro-inflammatory, Th1, and Th2 cytokines and daytime sleepiness during acute- and protracted abstinence and following acute cocaine administration. Given the prominence of sleep disturbance in cocaine dependent subjects and evidence of sleep architecture abnormalities into recovery, understanding the bi-directional relationships between cytokines and sleep in cocaine dependence has implications for answering why sleep is disordered in cocaine dependent patients and for the development of novel treatments for sleep disturbance in cocaine dependence.
Funding Period: 2002-09-30 - 2006-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Sleep deprivation potentiates activation of cardiovascular and catecholamine responses in abstinent alcoholics
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Neuropsychiatric Institute, Los Angeles 90095 7057, USA
    Hypertension 45:252-7. 2005
  2. ncbi Sleep loss activates cellular inflammatory signaling
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, CA 90095 7076, USA
    Biol Psychiatry 64:538-40. 2008
  3. ncbi Polysomnographic sleep dysregulation in cocaine dependence
    Edwin M Valladares
    Cousins Center for Psychoneuroimmunology, University of California Los Angeles, Semel Institute for Neuroscience and Human Behavior, Los Angeles, USA
    ScientificWorldJournal 7:213-6. 2007
  4. ncbi Sex differences in cardiac sympathovagal balance and vagal tone during nocturnal sleep
    Edwin M Valladares
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, 300 Medical Plaza, Suite 3 109, Los Angeles, CA 90095 7057, USA
    Sleep Med 9:310-6. 2008
  5. ncbi Loss of slow-wave sleep
    Sam M Eljammal
    Cousins Center for Psychoneuroimmunmolog, University of California, Los Angeles, CA 90095-7057, USA
    J Clin Sleep Med 2:213-4. 2006
  6. ncbi Sex differences in monocyte expression of IL-6: role of autonomic mechanisms
    Mary Frances O'Connor
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 300 Medical Plaza, Los Angeles, CA 90095 7076, USA
    Am J Physiol Regul Integr Comp Physiol 293:R145-51. 2007
  7. ncbi Cocaine dependence and acute cocaine induce decreases of monocyte proinflammatory cytokine expression across the diurnal period: autonomic mechanisms
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA 90095 7057, USA
    J Pharmacol Exp Ther 320:507-15. 2007
  8. ncbi Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 7057, USA
    Arch Intern Med 166:1756-62. 2006
  9. ncbi Association between nocturnal vagal tone and sleep depth, sleep quality, and fatigue in alcohol dependence
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Neuropsychiatric Institute, Los Angeles, CA 90095 7057, USA
    Psychosom Med 68:159-66. 2006
  10. ncbi Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of age
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles UCLA Neuropsychiatric Institute, Los Angeles, CA 90095 7057, USA
    Health Psychol 25:3-14. 2006

Scientific Experts

Detail Information

Publications13

  1. ncbi Sleep deprivation potentiates activation of cardiovascular and catecholamine responses in abstinent alcoholics
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Neuropsychiatric Institute, Los Angeles 90095 7057, USA
    Hypertension 45:252-7. 2005
    ..It is possible that modest habitual sleep loss could contribute to triggering cardiac arrhythmias or other cardiovascular events in alcohol dependence...
  2. ncbi Sleep loss activates cellular inflammatory signaling
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, CA 90095 7076, USA
    Biol Psychiatry 64:538-40. 2008
    ..This study was undertaken to test the effects of sleep loss on activation of nuclear factor (NF)-kappaB, a transcription factor that serves a critical role in the inflammatory signaling cascade...
  3. ncbi Polysomnographic sleep dysregulation in cocaine dependence
    Edwin M Valladares
    Cousins Center for Psychoneuroimmunology, University of California Los Angeles, Semel Institute for Neuroscience and Human Behavior, Los Angeles, USA
    ScientificWorldJournal 7:213-6. 2007
    ..Few studies have used polysomnography to evaluate sleep in cocaine-dependent persons, yet these studies have the potential to advance treatments that will ultimately reduce morbidity in cocaine-dependent subjects...
  4. ncbi Sex differences in cardiac sympathovagal balance and vagal tone during nocturnal sleep
    Edwin M Valladares
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, 300 Medical Plaza, Suite 3 109, Los Angeles, CA 90095 7057, USA
    Sleep Med 9:310-6. 2008
    ..To analyze sex differences in nocturnal vagal tone and cardiac sympathovagal balance during sleep in healthy men and women...
  5. ncbi Loss of slow-wave sleep
    Sam M Eljammal
    Cousins Center for Psychoneuroimmunmolog, University of California, Los Angeles, CA 90095-7057, USA
    J Clin Sleep Med 2:213-4. 2006
  6. ncbi Sex differences in monocyte expression of IL-6: role of autonomic mechanisms
    Mary Frances O'Connor
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 300 Medical Plaza, Los Angeles, CA 90095 7076, USA
    Am J Physiol Regul Integr Comp Physiol 293:R145-51. 2007
    ..Interventions that target autonomic mechanisms might constitute new strategies to constrain IL-6 production with impacts on inflammatory disease risk in women...
  7. ncbi Cocaine dependence and acute cocaine induce decreases of monocyte proinflammatory cytokine expression across the diurnal period: autonomic mechanisms
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA 90095 7057, USA
    J Pharmacol Exp Ther 320:507-15. 2007
    ..Targeting sympathovagal balance might represent a novel strategy for partial amelioration of impairments of innate immunity in cocaine dependence...
  8. ncbi Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 7057, USA
    Arch Intern Med 166:1756-62. 2006
    ..The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known...
  9. ncbi Association between nocturnal vagal tone and sleep depth, sleep quality, and fatigue in alcohol dependence
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Neuropsychiatric Institute, Los Angeles, CA 90095 7057, USA
    Psychosom Med 68:159-66. 2006
    ....
  10. ncbi Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of age
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles UCLA Neuropsychiatric Institute, Los Angeles, CA 90095 7057, USA
    Health Psychol 25:3-14. 2006
    ..A research agenda is recommended to examine the mechanisms of action of behavioral treatments on sleep with increased attention to the high prevalence of insomnia in older individuals...
  11. ncbi Dissociation of inflammatory markers and natural killer cell activity in major depressive disorder
    Jennifer L Pike
    Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Neuropsychiatric Institute, Los Angeles, CA 90095-7057, USA
    Brain Behav Immun 20:169-74. 2006
    ..The independent effect of depression on inflammatory markers and natural killer immune responses has implications for understanding individual differences in the adverse health effects of major depressive disorder...
  12. ncbi Inflammatory markers and sleep disturbance in major depression
    Sarosh J Motivala
    Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute, University of California, Los Angeles, CA, USA
    Psychosom Med 67:187-94. 2005
    ..This study was conducted to determine whether immune activation occurs in major depression, and to evaluate the associations between disordered sleep and markers of inflammation in patients with major depressive disorder...
  13. ncbi Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependence
    Michael R Irwin
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, University of California, Los Angeles, California 90095 7076, USA
    Biol Psychiatry 66:191-5. 2009
    ..This study was undertaken to test whether blockade of biologically active tumor necrosis factor-alpha (TNF-alpha) normalizes REM sleep in alcohol-dependent adults...