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Figure 1: The BBB Hypothesis of Psychiatric Disorders. Interactions within the neurovascular unit in the presence of abnormal blood-brain communication. BBB breakdown results in the diffusion of serum proteins (e.g., albumin, see text) into the brain, activation of signaling pathways, and inducing the transformation of astrocytes. This “reactive” glial reaction is associated with impaired extracellular homeostasis (e.g., reduced buffering of extracellular potassium and glutamate) and a local inflammatory response (e.g., secretion of cytokines, activation of microglia) and is enhanced in the presence of an inflammation in the periphery. Together, neuronal network dysfunction develops due to pathological synaptic plasticity.