ABSTRACT
The discovery, more than half a century ago, of the antimanic action of lithium ions by John Cade and the empirical proof of its antimanic and prophylactic efficacy by Mogens Schou and collaborators (for review see reference 1) has kindled much hope that, with the advent of a specific treatment and discovery of its mechanism of action, the road would be paved to rapid progress in the elucidation of the neurobiology of bipolar illness. However, while the accumulation of data on the neurobiological actions of lithium is impressive, it has been difficult to decide which of this multitude of effects on many neurobiologic parameters are instrumental in lithium’s efficacy as a mood stabilizer, and which are merely epiphenomena or responsible for side-effects. One potential solu-
tion to this problem is to identify biochemical actions that are common to several mood stabilizers, despite their different chemical structure and side-effect profile, and may therefore be most likely to be involved in their common beneficial clinical action. The presently established mood stabilizers are chemically diverse (a metal ion in the case of lithium, a simple branched-chained fatty acid in the case of valproate and a complex heterocyclic structure in the case of carbamazepine) and have thus quite different initial direct targets of action (for review see reference 2). However, recent progress in the elucidation of their downstream neurobiological actions has revealed remarkable similarities: they all have a prominent role in the regulation of neural resilience, growth and differentiation, albeit not always by virtue of similar mechanisms2-4.
