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).


As reviewed by Sheline (2000), there is increasing evidence for structural brain changes associated with major depression. Brain changes associated with early-onset major depression have been reported in the hippocampus, amygdala, caudate nucleus, putamen, and frontal cortex, which structures are extensively interconnected. Furthermore, several studies utilizing the magnetic resonance imaging (MRI) technology have reported losses of left and right hippocampal volumes in subjects with a history of severe recurrent depression. (Sheline 2000.) Moreover, functional neuroimaging studies have identified abnormal blood flow in the medial prefrontal cortex in patients with depression. The medial prefrontal cortex is a region where activity is crucially modulated by the neurotransmitters believed to be implicated in depression. (For a review, see Elliott 1998.) 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).

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