Sleep and the cholinergic rapid eye movement sleep induction test in patients with primary alcohol dependence

Background: The present study investigated polysomnographically assessed sleep parameters in alcohol-dependent patients after withdrawal and in healthy control subjects during baseline and after a cholinergic stimulation paradigm. The aim of the study was to test whether sleep parameters, especially rapid eye movement (REM) sleep variables, may serve as predictors for relapse in alcohol-dependent patients. Methods: Forty patients diagnosed with alcohol dependence were admitted to a specialized ward for alcohol withdrawal and were investigated by polysomnography at three time points: 2-3 weeks after withdrawal (T0) and at follow-up investigations 6 (T1) and 12 (T2) months after discharge from the hospital. A subgroup of patients (n = 17) was studied at T0 after challenge with galanthamine, a reversible cholinesterase inhibitor (cholinergic REM induction test, CRIT). Patients were compared with two control groups: a) 30 healthy control subjects (matched for age- and gender-distribution) for comparison at baseline conditions; and b) 17 age- and gender-matched control subjects for comparison with the CRIT. Results: At baseline the patients showed significant disturbances of sleep continuity and sleep architecture (decreased slow-wave sleep, SWS) and exhibited an increase of "REM sleep pressure" (a combined index of REM latency, REM density, and REM sleep percent). Galanthamine provoked significant alterations of sleep continuity, sleep architecture (reduced SWS), and increased most of the components of REM pressure, taking patients and control subjects together. Apart from SWS %SPT (sleep period time) no significant drug-group interactions occurred. Patients who remained abstinent (n = 11) for at least 6 months at follow-up exhibited significantly less abnormalities of REM sleep at T0 compared to the group of patients that relapsed at 6 months follow-up. Conclusions: It is concluded that increased REM sleep pressure after alcohol withdrawal is a robust predictor of vulnerability to relapse. Thus, a subgroup of alcoholic patients appears to exhibit distinct neurobiological abnormalities assessable by polysomnography that are related to an increased vulnerability for alcoholism and early relapse.