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Biological Theory of Depression

There have been a variety of theories concerning the neurobiologic etiology of depression. The classic biogenic amine theory of depression suggests that a shortage of noradrenalin (NA) and serotonin (5-HT) in the synaptic clefts is the neurobiological basis of depression (Schildkraut 1965, Bunney & Davis 1965, Coppen 1967). Although the serotonin system is still the most widely studied system, there is evidence suggesting that other neurotransmitter systems also play important roles (Barros et al. 2002). It is suggested that instead of being a consequence of a simple decrease in some crucial cerebral transmitter concentrations depression may be the result of a disturbed balance between different regulatory systems and consequent transmitter overactivity in some brain regions (Syvälahti 1994). According to a hypothesis by Harro & Oreland (1996) the neurobiological starting-point of depression lies in the malfunction of the noradrenergic innervation from the locus coeruleus, which, in turn, leads to dysregulation of serotonergic and dopaminergic neurotransmission. A molecular and cellular theory of depression posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, the neurotrophic factors necessary for the survival and function of particular neurons (Duman et al. 1997).

Depression is often accompanied by certain biological alterations, which may well explain the comorbidity of depression and various diseases. The corticosteroid overdrive and noradrenergic hyperactivity present in depression may impair the normal functions of the immune system (Syvälahti 1994). The reports on immune alterations in the context of depression are contradictory, however. According to the meta-analysis of Herbert & Cohen (1993), it seems that such alterations mainly occur in cellular immunity. The association between depression and coronary heart disease, rheumatoid arthritis, and stroke as well as the higher incidence of depression among females have been explained with the macrophage theory of depression, suggesting that excessive secretion of macrophage monokines is the cause of depression (Smith 1991). Many aspects of cellular immunity are activated in depression, including the increased release of proinflammatory cytokines from activated macrophages in the periphery and brain, the excessive synthesis of prostaglandin E2 (PGE2) and nitric oxide (NO), and the increased release of acute-phase proteins from the liver, while there is also evidence of the suppression of natural killer (NK) cell activity, T-lymphocytes, and neutrophils. It is also suggested, that many of these unfavorable changes in immune function involving depression can be normalized with antidepressant treatment. (For a review, see Leonard 2001.)


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