Evidence for a biochemical lesion in depression.
The monoamine hypothesis of depression predicts an impairment in central monoaminergic 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 metabolites in cerebrospinal fluid, urine, and plasma of patients with depression has yielded equivocal results regarding the possibility of altered metabolism of these neurotransmitters. Other studies have investigated the possibility of altered numbers and/or affinities of the serotonin and norepinephrine receptors and uptake sites. For example, there is evidence for a reduction 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 has focused on the possibility that a lesion may occur in the postreceptor, subcellular components of the monoamine systems, such as the second messenger processes. Also, experimental evidence has shown "cross-talk" between the noradrenergic and serotonergic systems. There is therefore substantial clinical and experimental evidence that lesions in the serotonergic and noradrenergic systems are responsible for depression and that antidepressant treatment can reverse these alterations.
Leonard
B E
BE
Department of Pharmacology, National University of Ireland, Galway.
D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D009638:Norepinephrine / Q000172:deficiency / Q000502:physiology*; D017982:Receptors, Biogenic Amine / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000172:deficiency / Q000502:physiology*
D000928:Antidepressive Agents; D017982:Receptors, Biogenic Amine; D012701:Serotonin; D009638:Norepinephrine