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Neuropharmacology. 2012 Jan;62(1):3-12. doi: 10.1016/j.neuropharm.2011.07.014. Epub 2011 Jul 27.

Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress.

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Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.


The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult, as well as developing brain, possess a remarkable ability to show reversible structural and functional plasticity in response to stressful and other experiences, including neuronal replacement, dendritic remodeling, and synapse turnover. This is particularly evident in the hippocampus, where all three types of structural plasticity have been recognized and investigated, using a combination of morphological, molecular, pharmacological, electrophysiological and behavioral approaches. The amygdala and the prefrontal cortex, brain regions involved in anxiety and fear, mood, cognitive function and behavioral control, also show structural plasticity. Acute and chronic stress cause an imbalance of neural circuitry subserving cognition, decision making, anxiety and mood that can increase or decrease expression of those behaviors and behavioral states. In the short term, such as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive; but, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic or mood anxiety disorders. We shall review cellular and molecular mechanisms, as well as recent work on individual differences in anxiety-like behavior and also developmental influences that bias how the brain responds to stressors. Finally, we suggest that such an approach needs to be extended to other brain areas that are also involved in anxiety and mood. This article is part of a Special Issue entitled 'Anxiety and Depression'.

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