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Neurobiol Dis. 2013 Sep;57:28-37. doi: 10.1016/j.nbd.2012.05.022. Epub 2012 Jun 9.

Environmental and pharmacological modulations of cellular plasticity: role in the pathophysiology and treatment of depression.

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Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT 06508, USA.


Atrophy of neurons and gross structural alterations of limbic brain regions, including the prefrontal cortex (PFC) and hippocampus, have been reported in brain imaging and postmortem studies of depressed patients. Preclinical findings have suggested that prolonged negative stress can induce changes comparable to those seen in major depressive disorder (MDD), through dendritic retraction and decreased spine density in PFC and hippocampal CA3 pyramidal neurons. Interestingly, recent studies have suggested that environmental and pharmacological manipulations, including antidepressant medication, exercise, and diet, can block or even reverse many of the molecular changes induced by stress, providing a clear link between these factors and susceptibility to MDD. In this review, we will discuss the environmental and pharmacological factors, as well as the contribution of genetic polymorphisms, involved in the regulation of neuronal morphology and plasticity in MDD and preclinical stress models. In particular, we will highlight the pro-depressive changes incurred by stress and the reversal of these changes by antidepressants, exercise, and diet.

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