This is a renewal of a K24 Career Investigator Award on sleep disturbances in alcohol-dependent patients. Insomnia is common, frequently persistent in newly recovering patients, and associated with relapse. In the first 5 years, the investigator acquired knowledge about sleep medicine, sleep research methods, traditional sleep stage scoring, and pharmacotherapy trial methods. He then designed and conducted a randomized, controlled pilot trial to study night-time administration of the sedating anticonvulsant drug, gabapentin, for its effects on both sleep and relapse to alcohol. This work produced the first evidence from a randomized controlled trial that gabapentin was superior to placebo for reducing time to relapse. Although robust effects on traditional measures of subjective and objective sleep were not found, analysis of sleep microarchitecture revealed that gabapentin increased delta (slow frequency) activity during rapid eye movement sleep, the period of sleep during which the cortex is paradoxically activated. Thus, gabapentin may have exerted its effect on daytime abstinence by slowing cortical hyperactivity during sleep. The current proposal builds on this work by investigating potential mechanisms for sleep disturbance in alcohol-dependent patients that could be targeted by medications. A novel sleep laboratory paradigm is described (and will be refined) that can inform the field about mechanisms of alcohol-related sleep disturbances as well as screen for medications that improve sleep. To demonstrate proof-of-concept, two medications with known potential for treating either alcohol dependence or insomnia (gabapentin, trazodone) will be studied for their short-term effects on disregulated sleep in alcohol-dependent patients. Training will comprise 10-15% effort for 5 years including mostly time in the sleep lab, but also local and national conferences on the neurobiology of sleep and alcoholism, and selected readings. Another 5-10% effort is for training new investigators supported by T32 and other fellowships. With Drs. Armitage and Hoffmann, the candidate will acquire new knowledge and skills about quantitative sleep EEG analysis and interpretation, as well as methods for measuring and analyzing homeostatic sleep drive and circadian rhythm regulation. He will apply these methods to alcohol dependent patients, an understudied population that may benefit clinically from a more sophisticated understanding of their sleep problems.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AA000304-09
Application #
7469530
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Fertig, Joanne
Project Start
1999-09-27
Project End
2010-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
9
Fiscal Year
2008
Total Cost
$175,279
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Zhabenko, Olena; Krentzman, Amy R; Robinson, Elizabeth A R et al. (2013) A longitudinal study of drinking and depression as predictors of insomnia in alcohol-dependent individuals. Subst Use Misuse 48:495-505
Zhabenko, Nataliya; Wojnar, Marcin; Brower, Kirk J (2012) Prevalence and correlates of insomnia in a polish sample of alcohol-dependent patients. Alcohol Clin Exp Res 36:1600-7
Wong, Maria M; Brower, Kirk J (2012) The prospective relationship between sleep problems and suicidal behavior in the National Longitudinal Study of Adolescent Health. J Psychiatr Res 46:953-9
Conroy, Deirdre A; Hairston, Ilana S; Arnedt, J Todd et al. (2012) Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls. Chronobiol Int 29:35-42
Brower, Kirk J; Wojnar, Marcin; Sliwerska, Elzbieta et al. (2012) PER3 polymorphism and insomnia severity in alcohol dependence. Sleep 35:571-7
Armitage, Roseanne; Hoffmann, Robert; Conroy, Deirdre A et al. (2012) Effects of a 3-hour sleep delay on sleep homeostasis in alcohol dependent adults. Sleep 35:273-8
Brower, Kirk J; McCammon, Ryan J; Wojnar, Marcin et al. (2011) Prescription sleeping pills, insomnia, and suicidality in the National Comorbidity Survey Replication. J Clin Psychiatry 72:515-21
Brower, Kirk J; Conroy, Deirdre A; Kurth, Megan E et al. (2011) Ramelteon and improved insomnia in alcohol-dependent patients: a case series. J Clin Sleep Med 7:274-5
Brower, Kirk J; Hoffmann, Robert; Conroy, Deirdre A et al. (2011) Sleep homeostasis in alcohol-dependent, depressed and healthy control men. Eur Arch Psychiatry Clin Neurosci 261:559-66
Brower, Kirk J; Krentzman, Amy; Robinson, Elizabeth A R (2011) Persistent insomnia, abstinence, and moderate drinking in alcohol-dependent individuals. Am J Addict 20:435-40

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