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Postsynaptic neuron regulating the transcription of genes that influence survival of other proteins including brain derived neurotrophic factor (BDNF) which exerts effects on neuronal growth. The role of BDNF in depression is supported by the observation that stress both reduces its expression and impairs neurogenesis.

While the monoamine hypothesis of depression is conceptually straightforward, it is in reality it is an oversimplification of a complicated picture. Other systems that are implicated in the aetiology of depression (and which provide potential targets for drug therapy) include the hypothalamopituitary-thyroid axis and the hypothalamopituitary-adrenal axis (HPA). The finding that 50% of depressed patients have elevated plasma Cortisol concentrations constitutes evidence that depression may be associated with increased HPA drive.

Drugs with similar modes of action to antidepressants find other uses in medicine. Amfebutamone/

buproprion inhibits reuptake of both dopamine and noradrenaline and was originally developed and used as an antidepressant; it is now used to assist smoking cessation (see p. 178). Sibutramine, licenced as an anorectic agent, is a serotonin and noradrenaline reuptake inhibitor (see p. 697). Despite its similarity of action to venlafaxine and evidence of an antidepressant effect from animal studies, sibutramine has yet to be recognised as effective for depression.

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