Insomnia and other sleep abnormalities are common, persistent, and, as a key component of protracted alcohol withdrawal, associated with relapse in alcohol-dependent patients. Both subjective and objective sleep measures can predict relapse;however, objective measures provide additional insight into the potential mechanisms underlying disrupted sleep. The overall, long-term objectives of the proposed research are to investigate the neurophysiologic mechanisms ~ofsleep disturbance that are associated with relapse in patients with alcohol dependence, and to target those mechanisms with medication in order to reduce relapse risk. The specific research aims are 1) to investigate three potential mechanisms of sleep disturbance in alcoholic patients with insomnia: impaired homeostatic drive, impaired circadian regulation, and brain hyperactivation;2) to investigate short-term effects of medication on sleep and its regulatory mechanisms in alcoholics;and 3) to investigate the short-term clinical course of alcoholism as a function of baseline sleep parameters. In Study Phases I &II (Screening &Baseline;10+ days), subjects are characterized clinically to diagnose insomnia and alcohol dependence;determine baseline values for drinking and sleeping;and rule out confounding sleep-impairing causes such as acute alcohol withdrawal, other substance use, and/or physical, mental, and other sleep disorders, e.g., sleep apnea. Phase III (Medication;10 days), is a randomized, double-blind parallel design comparison of gabapentin vs. placebo. Phases II &III each have 7 days of monitoring with sleep logs and actigraphy, followed by 3 nights in the sleep laboratory: an adaptation night, a baseline sleep night, and a challenge night in which sleep is recorded after a 3-hour extension of prior wakefulness. Dim-light melatonin onset (DLMO), a measure of circadian phase is also assessed. Power spectral analysis is used to quantify all-night EEG activity. On each challenge night, homeostatic sleep drive is assessed by evaluating the time course and distribution of delta power in NREM sleep after delay, compared to baseline levels. Phase IV is a 2-day med taper, &Phase V (Follow-up) consists of one visit after 12 weeks to assess course of drinking. In summary, sleep disturbance in alcoholic patients reflects neurophysiologic dysfunction, increases risk of relapse, and may be amenable to pharmacotherapy. Targeting treatment to the specific sleep regulatory disturbance is likely to improve alcoholism outcomes. Relevance: Alcoholism is a devastating chronic disorder that in any one year affects -10% of adults, costs over $185 billion, and causes more than 100,000 deaths in the U.S. Despite treatment, most alcoholic patients achieve only short-term abstinence, and medically based treatment improvements are needed that target biological risk factors for relapse. Overall public health will be improved by developing science-based treatments that can augment existing, but only partially effective, treatment approaches.
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