Cholinergic sensitivity predicts severity of mania

Our laboratory and others have reported that pupillary constrictions following application of the cholinergic agonist pilocarpine are increased in depressed patients. Moreover, mood improvements in manic patients, given lithium or Depakote, are also correlated with increases in pupil sensitivity. The present report describes the relationship between symptom severity and cholinergic sensitivity in a larger group (N=20) of manic patients (bipolar I; 296.4x). Pupil responses to pilocarpine eye drops (0-2%) were recorded using infrared pupillometry. The results were compared with pupil sizes measured under conditions of cholinergic blockade (0.5% tropicamide). Pupil responses were computed as percentages of the maximal range of areas measured under saturating agonist and antagonist conditions. Dose response curves were subjected to a log-logit transformation and ED(50) values were determined by weighted least squares regression. Bech-Rafaelsen mania ratings were found to be linearly related to ED(50) values (r=0.48). Patients with more severe mania required higher concentrations of pilocarpine in order to elicit a 50% reduction in pupil size. The present findings support a putative cholinergic role in the regulation of mood state. Moreover, the results suggest that pupillary responses may provide a simple and non-invasive means to evaluate cholinergic sensitivity in patients with affective disorders.