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We compared central cholinergic responsiveness (using the latency to induction of rapid eye movement sleep after arecoline challenge as a response marker) in 90 subjects: patients with major depressive disorder (MDD) (n = 53), nonaffective psychiatric controls (n = 17), and normal controls (n = 20). MDD patients as a whole showed a supersensitive cholinergic response compared to nonaffective patients and normal subjects. Further analysis indicated a strong association between cholinergic supersensitivity and endogenous subtype of MDD, including a significant correlation with specific endogenous features such as distinct quality of mood, anhedonia, lack of reactivity, and agitation. Unlike rapid eye movement (REM) latency (a more conventional physiological marker), cholinergic sensitivity did not correlate with age or severity of illness but only with the presence of endogenous features. Previously described sleep physiological correlates such as REM latency and REM density of the first REM period also distinguished between endogenous and nonendogenous MDD. There was a statistically significant correlation between REM latency and arecoline REM induction response.

Nine narcoleptic and nine control subjects underwent 4 nights of sleep recordings. On nights 3 and 4, they received continuous intravenous infusions of saline. Additionally, on both nights they received 0.2 mg glycopyrrolate at the end of the first REM period (REM1) and 0.5 mg arecoline or placebo in random order 20 min after the end of REM1. Heart rates were counted for a 40-min period following the end of REM1. There was a significant and similar cardioacceleratory effect after arecoline in both narcoleptic and normal subjects, beginning at 5 min from the start of the infusion and peaking at 9 min. Placebo had no effect. Narcoleptic subjects had consistently higher baseline heart rates than controls on infusion and noninfusion nights, most likely owing to age differences between the two groups. The results suggest that narcoleptic persons do not have increased cholinergic sensitivity, or that the canine model of narcolepsy differs from the human model, or that the muscarinic receptors that play a role in the pathophysiology of narcolepsy differ in sensitivity from those that regulate heart rate.