A novel hypothesis for the psycho-modulating effects of lithium: the role of essential fatty acids, eicosanoids and sub-cellular second messengers

Abstract

Evidence is presented for a novel proposal for the mechanism of action of lithium in manic depressive psychosis. Lithium has well established effects on catecholaminergic--and hormone--stimulated adenyl cyclase activity and on cyclic AMP formation. Although there is conflicting evidence in the literature concerning the effects of the ion on cyclic nucleotide phosphodiesterase, not much is known of the effects of lithium on cyclic GMP. These two second messengers have been proposed to be mutually antagonistic in their actions but that a physiological balance between the two is essential for maintaining homeostasis of the human psyche. An in vivo animal study was undertaken to determine the effects of chronic lithium treatment on the dynamics and kinetics of these two cyclic nucleotides and phosphodiesterase in rat cerebral cortex. From these results, a possible functional coupling mechanism between the two second messenger systems and the effects of lithium are proposed. Lithium by means of its specific site of action, is unique among psychoactive drugs in that it can control both phases of bipolar illness. This point of action is proposed to be the metabolism of free fatty acids where lithium, by altering the availability of precursors for eicosanoid metabolism, is able to modulate both noradrenergic- and cholinergic-dependent pathways. By doing this, the ion is able to reestablish lost control over adrenergic and cholinergic balance critical for thought process and mood stability.