Abstract

In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

Author affiliations

1. Department of Medical Pharmacology, Leiden Amsterdam Center for Drug Research and Leiden University Medical Center, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
2. Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
3. Max Planck Institute of Psychiatry, Kraepelinstrasse 2–10, 80804 Munich, Germany.

Correspondence to: E. Ron de Kloet¹ Email: e.kloet@lacdr.leidenuniv.nl

Published online 13 May 2005

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