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Evidence for a Biochemical Lesion in Depression

Brian E. Leonard, PhD, DSc, MRIA

Published: March 31, 2000

Article Abstract

The monoamine hypothesis of depression predicts an impairment in central monoaminergic function.The lesion may comprise deficiencies in the absolute concentrations of norepinephrine and/orserotonin (5-HT). Depletion studies have shown a correlation between such deficiencies and depressivesymptoms. Measurement of the concentrations of the neurotransmitters and their metabolites incerebrospinal fluid, urine, and plasma of patients with depression has yielded equivocal results regardingthe possibility of altered metabolism of these neurotransmitters. Other studies have investigatedthe possibility of altered numbers and/or affinities of the serotonin and norepinephrine receptorsand uptake sites. For example, there is evidence for a reduction in the activity of the serotonin reuptaketransporter in patients with depression and an increase in the density of 5-HT2 receptors in thebrains of suicide victims. Similarly, in the noradrenergic system, up-regulation of β-adrenoceptors isconsistently observed. Most recently, attention has focused on the possibility that a lesion may occurin the postreceptor, subcellular components of the monoamine systems, such as the second messengerprocesses. Also, experimental evidence has shown “cross-talk” between the noradrenergic and serotonergicsystems. There is therefore substantial clinical and experimental evidence that lesions in theserotonergic and noradrenergic systems are responsible for depression and that antidepressant treatmentcan reverse these alterations.

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