Depression: The case for a monoamine deficiency

The monoamine hypothesis of depression predicts that the underlying pathoph ysiologic basis of depression is a depletion in the levers of serotonin, no repinephrine, and/or dopamine in the central nervous system. This hypothesi zed pathophysiology appears to be supported by the mechanism of action of a ntidepressants: agents that elevate the levels of these neurotransmitters i n the brain have all been shown to be effective in the alleviation of depre ssive symptoms. However, intensive investigation has failed to find convinc ing evidence of a primary dysfunction of a specific monoamine system in pat ients with major depressive disorders. Understanding of the etiology of dep ression has been hampered by the absence of direct measurements of monoamin es in humans. However, the monoamine depletion paradigm, which reproduces t he clinical syndrome, allows a more direct method for investigating the rol e of monoamines. Results from such studies show that antidepressant respons es are transiently reversed, with the response being dependent on the class of antidepressant. In contrast, monoamine depletion does not worsen sympto ms in depressed patients not taking medication, nor does it cause depressio n in healthy volunteers with no depressive illness. In conclusion, it is cl ear that antidepressant agents in current use do indeed require intact mono amine systems for their therapeutic effect. However, some debate remains as to the precise role that a deficiency in monoamine system(s) may play in d epression itself.