Cocaine Dependence: EEG Sleep and Cytokines
Principal Investigator: M Irwin
Affiliation: University of California
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
- Sleep deprivation potentiates activation of cardiovascular and catecholamine responses in abstinent alcoholicsMichael 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...
- Sleep loss activates cellular inflammatory signalingMichael 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...
- Polysomnographic sleep dysregulation in cocaine dependenceEdwin 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...
- Sex differences in cardiac sympathovagal balance and vagal tone during nocturnal sleepEdwin 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...
- Loss of slow-wave sleepSam M Eljammal
Cousins Center for Psychoneuroimmunmolog, University of California, Los Angeles, CA 90095-7057, USA
J Clin Sleep Med 2:213-4. 2006
- Sex differences in monocyte expression of IL-6: role of autonomic mechanismsMary 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...
- Cocaine dependence and acute cocaine induce decreases of monocyte proinflammatory cytokine expression across the diurnal period: autonomic mechanismsMichael 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...
- Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammationMichael 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...
- Association between nocturnal vagal tone and sleep depth, sleep quality, and fatigue in alcohol dependenceMichael 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....
- Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of ageMichael 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...
- Dissociation of inflammatory markers and natural killer cell activity in major depressive disorderJennifer 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...
- Inflammatory markers and sleep disturbance in major depressionSarosh 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...
- Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependenceMichael 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...