Brain neurotoxic amyloid-beta peptides: their potential role in the pathophysiology of depression and as molecular therapeutic targets.

The monoamine hypothesis ascribes an important role to the under activity of brain monoamines such as 5-HT, noradrenaline and dopamine to the pathophysiology of depression. This view emerged more than 50 years ago and has guided development of most medications currently used for the treatment of this disorder. However, large numbers of depressed individuals treated with currently available antidepressant agents, or even with various combinations, do not respond. Residual symptoms, relapses and recurrences are common while receiving adequate doses of these medications. In a recent issue of the BJP, Colaianna et al.describe results suggesting that a new neurobiological mechanism with treatment implications should be considered for the development of depression in humans, namely, elevations in potentially neurotoxic brain amyloid-ß peptides.