INFLAMMATION AND BLOOD BRAIN BARRIER INTEGRITY AS BIOMARKERS OF SUICIDAL BEHAVIOR. – IBBBIS

The prevention of suicidal behaviors (SB) is a major public health priority worldwide, especially since the phenomenon is feared to worsen in the context of the COVID 19 pandemic. The identification of hig-risk subjects remains a major challenge for clinicians as they currently assess only clinical factors not enough reliable to predict the occurrence of SB in a given subject. Improving the understanding of SB pathophysiology is necessary to identify biological factors (biomarkers) that will facilitate, alone or in combination with clinical factors, the identification of high-risk subjects and the implementation of effective prevention strategies. Recently, scientific data suggest the involvement of low-level but chronic inflammation in SB, both at the peripheral and cerebral level. This link would be independent of major depression, which is the psychiatric disorder most often associated with CS. However, the link between peripheral and brain inflammation (or neuroinflammation) remains relatively unexplored. Peripheral inflammation may lead to blood-brain barrier (BBB) damage responsible for neurovascular permeability which plays a role in the pathophysiology of SB Our project aims at studying a set of biomarkers of inflammation and biomarkers of neurovascular damage at the blood level. We will also study epigenetic factors involved in immune regulation and brain changes related to neuroinflammation. In particular, we will focus on small circulating RNAs (miRNAs) in exosomes. For this purpose, we will recruit a prospective cohort of 100 depressed subjects with a recent SB (within the last 8 days) or without a lifetime history of SB (affective controls) as well as 50 subjects without lifetime psychiatric disorder (healthy controls). A blood sample will be taken to measure peripheral markers. Quantitative MRI will be performed to measure for white matter, diffusion and functional connectivity abnormalities. These assays and the MRI will be repeated at one month to evaluate the evolution of these markers after the resolution of the acute suicidal crisis. We will identify biomarkers associated with SB by comparing the 3 groups of subjects. We will also study the association between MRI biomarkers and peripheral markers to better determine the blood-brain interactions involved in SB. The longitudinal approach will allow us to distinguish between trait and state biomarkers while taking into account elements of stress (depression/suicidal crisis). The originality of the project lies in the methodological design and the combination of different synergistic expertises to study the association between all these markers of inflammation and neurovascular dysfunctions, both peripheral and cerebral, in order to propose a multimodal diagnostic tool whose validity can then be tested in further clinical studies.