Pupillary cholinergic sensitivity to pilocarpine increases in manic lithium responders

Background: The cholinergic hypothesis of affective disorders predicts that mania is a hypocholinergic state relative to monoaminergic activity. Treatments that increase cholinergic sensitivity are expected to improve manic symptoms. Methods: Ten male hypomanic or manic patients were treated with lithium carbonate (0.7–1.1 mEq/L) for 2 weeks. Cholinergic sensitivity was assessed prior to, and following treatments, using graded concentrations of pilocarpine eyedrops (.03–2.0%). Pupil size changes were quantified using an infrared pupillometer and ED50 values were referenced to maximal dilation with .5% tropicamide. Results: Lithium treatment decreased Bech mania ratings and ED50 values (p< .001). Improvements in mania with lithium treatment were closely correlated with decreases in ED50 (r = .88, p< .001). Conclusions: These results support the cholinergic-adrenergic hypothesis and suggest that one possible mechanism for the antimanic effects of lithium may involve increasing cholinergic activity in relation to monoaminergic neurotransmission.