Faculty Bibliography

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

Retrograde facilitation (RF) of information learned prior to acute oral administration of trihexyphenidyl, a preferential muscarinic M1 receptor antagonist which impairs new learning, was studied in 24 healthy elderly subjects. The relationship between the RF induced by this anticholinergic drug and the APOE epsilon4 allele was also examined. Acute adverse performance effects of trihexyphenidyl (1- and 2mg) were determined using the Buschke Selective Reminding Test administered pre-drug and at 1, 2.5, and 5h post-drug. Recall of pre-drug words at the end of the fifth hour neuropsychological assessment (end-of-session recall) was of primary interest. Words studied before drug administration were better recalled following 2mg trihexyphenidyl compared to placebo, and this RF effect was not affected by the APOE epsilon4 allele. Better recall of pre-drug words following 2-mg trihexyphenidyl was associated with a greater amnestic effect of this dose. Our findings demonstrated that RF induced by trihexyphenidyl was related to anterograde amnestic effects of the drug and resulted in part from drug-induced reduction of retroactive interference