Search

Monoamine metabolite measurements are being increasingly used for making nosological, symptomatological and pharmacological profiles of the affective disorders. A number of unresolved methodological issues question the validity of using baseline metabolite levels for predicting treatment response. Some studies show correlations between baseline metabolite levels and response to treatment with specific antidepressant agents. Effects of antidepressant treatment on metabolite levels may be useful in predicting drug response.

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.

Basic physiological and neurochemical control mechanisms of human iris musculature are reviewed. The advantages and limitations of using pupillary responses to cholinergic and adrenergic drug challenges as peripheral indices of neuronal receptor sensitivity, are examined. A group of 15 depressed patients were tested with ocular instillation of pilocarpine and phenylephrine before and during treatment with Tranylcypromine. No change of pilocarpine sensitivity was found. A significant enhancement of phenylephrine sensitivity during weeks 3-5, but not during the first or second week of treatment was noted. The above potentiation of alpha-adrenergic responsiveness was correlated with clinical recovery.