[PUBLICATION] Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study


du 30 août 2023 au 25 septembre 2023

Une publication dans Molecular Psychiatry sur les mécanismes cérébraux de l'effet antidépresseur du Protoxyde d'azote, en IRMf et Ultrasons avec Thomas Desmidt, en collaboration avec Helmet T. Karim (Université de Pittsburg, USA).

Nitrous oxide (N2 O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this
effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide
(EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a
major depressive episode resistant to at least one antidepressant and 10 healthy controlsHC, aged 2550, only females) were
exposed to a 1-h single session of EMONO and followed for 1 week. We defined response as a reduction of at least 50% in the
MADRS score 1 week after exposure. Cerebral connectivity of the Anterior Cingulate Cortex (ACC), using ROI-based resting state
fMRI, and BTP, using ultrasound Tissue Pulsatility Imaging, were compared before and rapidly after exposure (as well as during
exposure for BTP) among HC, non-responders and responders. We conducted analyses to compare group × time, group, and time
effects. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we
observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal
ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in
the three groups between baseline and gas exposure, but the increase in BTP within the first 10 min was only significant in
responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the subgenual ACC-
precuneus, nodes within the default mode network, in depressed participants responders to EMONO. In addition, larger increases in
BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating
optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of
N2 O, as well as potential markers for treatment response with this fast-acting antidepressant.

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