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The postulated disturbance of cyclic AMP (cAMP) in manic-depressive illness was investigated by using plasma as the biological material. Cyclic AMP was measured by a protein-binding assay, which was found very satisfactory for the purpose of this study. In the drug-free state, depressed patients (n = 28) had significantly lower and manic patients (n = 9) significantly higher plasma concentrations of cAMP than controls. Unmedicated manic-depressive subjects had normal cAMP levels during normothymic phases (n = 7). Cyclic AMP was reduced by neuroleptics in mania and elevated by tricyclics in depression. Lithium exerted a normalizing effect on cAMP in both phases of the illness. It is concluded that manic-depressive illness is associated with a disturbance in the cAMP system. The use of plasma rather than urine for the investigation of the state of cAMP in psychiatric disorders is advocated.
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