Evidence for a biochemical lesion in depression

The monoamine hypothesis of depression predicts an impairment in central mo noaminergic function. The lesion may comprise deficiencies in the absolute concentrations of norepinephrine and/or serotonin (5-HT). Depletion studies have shown a correlation between such deficiencies and depressive symptoms . Measurement of the concentrations of the neurotransmitters and their meta bolites in cerebrospinal fluid, urine, and plasma of patients with depressi on has yielded equivocal results regarding the possibility of altered metab olism of these neurotransmitters. Other studios have investigated the possi bility of altered numbers and/or affinities of the serotonin and norepineph rine receptors and uptake sites. For example, there is evidence for a reduc tion in the activity of the serotonin reuptake transporter in patients with depression and an increase in the density of 5-HT2 receptors in the brains of suicide victims. Similarly, in the noradrenergic system, up-regulation of beta-adrenoceptors is consistently observed. Most recently, attention ha s focused on the possibility that a lesion may occur in the postreceptor, s ubcellular components of thr monoamine systems, such as the second messenge r processes. Also, experimental evidence has shown "cross-talk" between the noradrenergic and serotonergic systems. There is therefore substantial cli nical and experimental evidence that lesions in the serotonergic and noradr energic systems are responsible for depression and that antidepressant trea tment can reverse these alterations.