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Stress and Neurogenesis

Can adult neurogenesis buffer stress responses and depressive behaviour?

Molecular Psychiatry volume 17, pages 9–10 (2012)Cite this article

As all novel theories, the neurogenesis model of depression has triggered reactions ranging from messianic conviction to total scepticism. The recent paper by Snyder et al.1 helps us refine this model, by introducing a crucial link with a major biological system consistently disrupted in depression, the hypothalamic–pituitary–adrenal (HPA) axis.2 The main finding is that inhibition of neurogenesis induces the classical neuroendocrine phenotype described in major depression: increased HPA axis activity and glucocorticoid resistance, that is, impaired suppression of HPA axis activity by dexamethasone. As stress and high levels of glucocorticoid hormones are well known to inhibit neurogenesis, the authors suggest that stress, by inhibiting neurogenesis, may lead to enhanced HPA axis responsiveness to future stressors, and thus establish a potentially vicious circle leading to the development of depressive behaviour.1

But how can neurogenesis regulate the HPA axis? The results by Snyder et al.1 are consistent with a previous report,3 but are in apparent contrast with a recent paper by Surget et al.4 showing that neurogenesis inhibition does not influence suppression of HPA axis activity by dexamethasone. Can the differences between these studies give us any mechanistic clues? It is of particular interest that Synder et al.1 injected dexamethasone 90 min before a restraint stress, and blood was sampled immediately after the restraint, while Surget et al.4 injected dexamethasone on the last day of a 7-week long unpredictable chronic mild stress. This indicates that neurogenesis is crucial to maintain an effective HPA axis suppression during an acute, and quite intense, stress, but not to maintain a normal HPA axis activity or during milder stressors. It is also of note that we and others have extensively shown that dexamethasone does not enter into the brain when administered in the periphery,5 and thus it is likely that the impaired suppression of HPA axis activity by dexamethasone (in the paper by Synder et al.1) is localised in subcortical HPA axis areas, such as the hypothalamus or the pituitary, which are under the tonic inhibitory control from the hippocampus. While these authors do not test or even discuss this hypothesis,1 Surget et al.4 show that chronic stress inhibits neurogenesis, induces glucocorticoid resistance and reduces hippocampal regulation of subcortical HPA areas.4 Therefore, it is possible that adult hippocampal neurogenesis contributes to HPA axis regulation by maintaining effective neuronal (inhibitory) connections between the hippocampus and other HPA axis areas. Of course, it is possible that neurogenesis buffers the behavioural effects of stress not only by supporting a normal HPA axis activity but also through other behaviourally relevant paths, such as the recently described ability to enhance encoding of new memories and respond to contextual changes,6 which may be protective against behavioural despair in the face of repeated stressors.

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Authors and Affiliations

  1. Department of Psychological Medicine, King’s College London, Institute of Psychiatry, Section of Perinatal Psychiatry and Stress, Psychiatry and Immunology (SPI-lab), London, UK

    C Anacker & C M Pariante

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  1. C Anacker
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  2. C M Pariante
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Correspondence to C M Pariante.

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Anacker, C., Pariante, C. Can adult neurogenesis buffer stress responses and depressive behaviour?. Mol Psychiatry 17, 9–10 (2012). https://doi.org/10.1038/mp.2011.133

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