Neuropsychopharmacology Reviews

Neuropsychopharmacology (2008) 33, 88–109; doi:10.1038/sj.npp.1301574; published online 12 September 2007

Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms

Christopher Pittenger1 and Ronald S Duman1

1Department of Psychiatry, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA

Correspondence: Dr RS Duman, Connecticut Mental Health Center, Yale University School of Medicine, 34 Park Street, Third Floor, New Haven, CT 6508, USA. Tel: +1 203 974 7726; Fax: +1 203 974 7724; E-mail: ronald.duman@yale.edu

Received 11 July 2007; Revised 3 August 2007; Accepted 4 August 2007; Published online 12 September 2007.

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Abstract

Increasing evidence demonstrates that neuroplasticity, a fundamental mechanism of neuronal adaptation, is disrupted in mood disorders and in animal models of stress. Here we provide an overview of the evidence that chronic stress, which can precipitate or exacerbate depression, disrupts neuroplasticity, while antidepressant treatment produces opposing effects and can enhance neuroplasticity. We discuss neuroplasticity at different levels: structural plasticity (such as plastic changes in spine and dendrite morphology as well as adult neurogenesis), functional synaptic plasticity, and the molecular and cellular mechanisms accompanying such changes. Together, these studies elucidate mechanisms that may contribute to the pathophysiology of depression. Greater appreciation of the convergence of mechanisms between stress, depression, and neuroplasticity is likely to lead to the identification of novel targets for more efficacious treatments.

Keywords:

synapse, neurogenesis, antidepressant, signal transduction, gene expression

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