Affective disorders and S-adenosylmethionine: a new hypothesis

S-Adenosyl-L-methionine (AdoMet) is a safe and probably effective antidepressant agent in certain forms of clinical depression. This article presents a new hypothesis to account for the mechanism of action of S-adenosylmethionine in such illnesses, based upon the known biochemistry of this compound, and upon current knowledge of clinical and genetic aspects of affective disorders. Giulio Cantoni, S. Harvey Mudd and V. Andreoli postulate that at least some major mood disorders are due to abnormalities affecting the AdoMet-dependent methylation of a substance in the CNS. For convenience and without prejudging the chemical structure of this substance, they call it 'barinine'. The model requires that barinine be subject to AdoMet-dependent methylation and that methylbarinine be subject to metabolic demethylation to regenerate the original barinine. Methylbarinine should be mood elevating, whereas barinine itself should not be. Depression is a result of abnormalities lowering the normal steady-state concentration of methylbarinine, whereas mania results from an abnormal elevation of methylbarinine.