title: Monoaminergic mechanisms in affective disorders.
abstract: The monoamine hypothesis of depression originally proposed that depression is caused by a central deficiency of biogenic amines, and antidepressants were considered to work by correcting this deficiency. In the course of time, many studies have analysed monoamine metabolites in the urine, plasma and cerebrospinal fluid of patients and healthy controls under different conditions to test the hypothesis. These studies have failed to identify a robust metabolic disorder in depressive patients as a group. Certain subgroups of depressed patients have shown deviations in biogenic amine metabolism, the most consistent being reduced levels of the major serotonin and dopamine metabolites in the cerebrospinal fluid. Noradrenaline metabolism is influenced by the activity of the sympathetic nervous system, and thus increases in anxious patients regardless of their clinical diagnosis. On the other hand, development of new antidepressants and advances in receptor techniques, together with modern electrophysiologic and behavioural studies have given increasing support to a receptor supersensitivity hypothesis of depression, based on the evidence that antidepressants lead to subsensitivity or down regulation of beta-adrenoceptors, and adaptive changes may occur also in other receptor systems after two three weeks of antidepressant treatment. There is also growing evidence on the manifold interplay of noradrenergic and serotonergic systems in the mechanism of actions of effective antidepressant treatments, including the new and more selective therapeutic compounds. The rapidly increasing knowledge of the neurotransmitter receptors as well as of the relations between the different regulatory systems may lead to more specific intervention strategies in efforts to correct the biological malfunction in the heterogeneous collection of diseases classified as affective disorders.
mesh_terms: D001679:Biogenic Amines / Q000502:physiology*; D003866:Depressive Disorder / Q000503:physiopathology; D006801:Humans; D008959:Models, Neurological; D008960:Models, Psychological; D019964:Mood Disorders / Q000209:etiology / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000502:physiology*
chemical_list: D001679:Biogenic Amines; D018377:Neurotransmitter Agents