Disturbances of sleep are prominent in alcoholic patients, persist into recovery, and have recently been found to predict those alcoholics who are most likely to relapse. This study hypothesizes that the complex cytokine network is one system that is associated with declines of sleep depth and loss of delta sleep in alcoholics. Basic observations demonstrate that pro-inflammatory and helper T cell type 1/type 2 (Thl/Th2) cytokines have a physiological role in the regulation of sleep with both somnogenic and inhibitory effects depending on the cytokine, dose, and circadian phase. However, translation of these basic mechanisms into the clinical setting is limited, and virtually no study has examined the relationships between cytokine expression and disordered sleep in patients with chronic alcohol dependence. Because evidence further indicates that African American alcoholics are at increased risk for infectious disease morbidity, disordered sleep, and abnormal cytokine expression, this study further proposes to examine the effects of alcohol dependence on sleep and on the relationships between sleep and pro-inflammatory and Thl/Th2 cytokine expression in """"""""at risk"""""""" African American alcoholics vs. Euro-American alcoholics and controls. Sleep deprivation serves as a naturalistic probe of sleep regulatory processes to evaluate the capacity of sleep recovery in alcoholics and to test the effects of sleep on immune system functioning.
The specific aims of this study are to: 1) evaluate whether alcohol dependence and African American ethnicity are associated with disturbances of sleep including loss of delta sleep and deficits in recovery of delta sleep following sleep deprivation as compared to ethnicity matched controls; 2) establish the impact of sleep on the diurnal- and nocturnal expression of pro-inflammatory-, Thl, and Th2 cytokine levels in African American and Euro- American alcoholics vs. controls; 3) determine the predictive validity of circulating interlekin-6 on delta sleep. This study will advance our understanding of the reciprocal relationships between cytokines and sleep in alcohol dependence with implications for answering why sleep is disordered in alcoholics patients and for the development of novel treatments (e.g., cytokine antagonists) for sleep disturbance in alcoholism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA013239-05
Application #
6729844
Study Section
Special Emphasis Panel (ZAA1-BB (03))
Program Officer
Grandison, Lindsey
Project Start
2001-06-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
5
Fiscal Year
2004
Total Cost
$381,250
Indirect Cost
Name
University of California Los Angeles
Department
Psychiatry
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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