[The cholinergic-adrenergic equilibrium hypothesis of affective psychoses]

The biochemical effects of antidepressant drugs generated the hypothesis of disturbances in the noradrenergic system in the pathogenesis of affective disorders. However, interference with the cholinergic system also yields psychotropic sequelae. Central cholinomimetics revealed antimanic properties as opposed to antidepressant effects of anticholinergics. Therefore, in extension of the catecholamine hypothesis and again based on the paradigm of pharmacological isomorphism, a cholinergic-adrenergic balance hypothesis has been suggested for affective disorders. This postulates a cholinergic predominance relative to noradrenergic activity in depression and the converse in mania. Although there are indications of inverse behavioural effects of cholinergic as opposed to catecholaminergic stimulation in man and animal, there is only few evidence at the neurophysiological and biochemical level in favour of the net effects depending on such a balance. However, only the direct demonstration of a biochemical defect can prove the balance hypothesis. More probably, interindividually different defects must be expected. They need not necessarily involve the synaptic signal transduction directly. Strategies and findings which might demonstrate biochemical disturbances are presented and discussed.