21 October 2007

Anxiety/depression, SSRIs and neurogenesis

Alex Dranovsky & Rene Hen (2006) Hippocampal Neurogenesis: Regulation by Stress and Antidepressants. Biological Psychiatry 59, p 1136-143. LINK
Synopsis: Except in trauma, where neural stem cells migrate to replace damaged tissue, neurogenesis in adult humans only occurs in the hippocampus, and possibly the SVN. In rodent models of anxiety/depression (e.g. anxious strains exposed to prolonged periods of stress, including 'social subordination') hippocampal neurogenesis is inhibited and hippocampal size is reduced, probably through direct action of glucocorticoids on hippocampal neurons and reduced transcription of BDNF and related genes. This may leave the hippocampus less able to excert its normally inhibitory effect on the HPA axis, glucocorticoid levels rise further, and depression ensues. Inhibitors of the serotonin transporter (SSRIs) help the brain break out of this cycle by stimulating hippocampal neurogenesis and BDNF transcription, probably via the 5HT1A receptor (5HT1A knockouts have normal baseline neurogenesis but do not respond to SSRIs). Noradrenaline has comparable effects to serotonin on neurogenesis.
Note: So cAMP, generally inhibited by serotonin and noradrenaline in the CNS, inhibits neurogenesis in the hippocampus, whilst simultaneously promoting synaptic plasticity via DARP-32, CREB and other pathways...?
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