Alterations in the Blood-Brain Barrier in Mood Disorders and Neurodegenerative Diseases.

Abstract

Depressive disorders and suicidal behaviors represent major causes of health loss. Modifications of brain microvasculature, and specifically alterations of the blood-brain barrier have been supposed to participate in the vulnerability to those disorders along with cognitive impairment, especially in the older adults. In this article, we addressed evidence linking blood-brain barrier impairments with mood disorders and suicide. Secondly, we investigated their relationship with depression in old age, and with neurodegenerative processes. Particular attention was drawn toward the potential interactions between the coagulation processes and the blood-brain barrier dysfunctions, as innovative treatment strategies may emerge from research in those fields. Overall, the studies reviewed highlight the implication of multiple dysfunctions of the blood-brain barrier in mood disorders and suicide. Impairments of the blood-brain barrier show relationships with altered expression of endothelial cell junction proteins. These modifications also implicate receptors of the extracellular matrix, the vascular endothelial growth factor, changes in perivascular astrocytes, and has links with local and systemic inflammatory processes. Dysfunctions of the blood-brain barrier underly chronic stress and participate in psychiatric diathesis in old age. In addition, we outline that coagulation processes are likely to interact with the blood-brain barrier and further contribute to neurodegenerative disorders. In conclusion, new pathophysiological models offer perspectives toward detecting new biomarkers in mood disorders and suicide. In parallel, these models open avenues for developing innovative therapeutic agents, although further considering their potential risks and eventual benefits is needed.