British Medical Bulletin 2001;57: 61–79 The British Council 2001 Depression – emerging insights from neurobiology

An emerging hypothesis suggests that the pathogenesis and treatment of depression is likely to involve a plasticity of neuronal pathways. The inability of neuronal systems to exhibit appropriate, adaptive plasticity could contribute to the pathogenesis of depression. Antidepressant treatments may exert their therapeutic effects by stimulating appropriate adaptive changes in neuronal systems. Recent studies have demonstrated that chronic antidepressant administration up-regulates the cAMP signal transduction cascade resulting in an increased expression and function of the transcription factor CREB. Enhanced CREB expression leads to an up-regulation of specific target genes, including the neurotrophin BDNF. Chronic antidepressant treatments enhance BDNF expression within hippocampal and cortical neurons and can prevent the stress-induced decrease in BDNF expression. Stress has been shown to: (i) induce neuronal atrophy/death; and (ii) decrease neurogenesis of hippocampal neurons. Clinical studies indicate significant hippo-campal damage in cases of major, recurrent depression. It is possible that anti-depressant treatments through enhanced expression of growth and surviva