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Cardiovascular Psychiatry and Neurology
Volume 2009 (2009), Article ID 278531, 7 pages
http://dx.doi.org/10.1155/2009/278531
Hypothesis

Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder

1Department of Psychiatry, Soroka University Medical Center; Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
2Department of Physiology and Neurosurgery, Soroka University Medical Center; Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel

Received 2 April 2009; Accepted 4 July 2009

Academic Editor: Hari Manev

Copyright © 2009 Hadar Shalev et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The mechanisms underlying the development and progression of psychiatric illnesses are only partially known. Clinical data suggest blood-brain barrier (BBB) breakdown and inflammation are involved in some patients groups. Here we put forward the “BBB hypothesis” and abnormal blood-brain communication as key mechanisms leading to neuronal dysfunction underlying disturbed cognition, mood, and behavior. Based on accumulating clinical data and animal experiments, we propose that events within the “neurovascular unit” are initiated by a focal BBB breakdown, and are associated with dysfunction of brain astrocytes, a local inflammatory response, pathological synaptic plasticity, and increased network connectivity. Our hypothesis should be validated in animal models of psychiatric diseases and BBB breakdown. Recently developed imaging approaches open the opportunity to challenge our hypothesis in patients. We propose that molecular mechanisms controlling BBB permeability, astrocytic functions, and inflammation may become novel targets for the prevention and treatment of psychiatric disorders.