Int J Neuropsychopharmacol. 2021 Mar 1:pyab008. doi: 10.1093/ijnp/pyab008. Online ahead of print.
ABSTRACT
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are predominantly prescribed for people suffering from major depressive disorder (MDD). These antidepressants exert their effects by blocking the serotonin transporter (SERT) leading to increased levels of serotonin in the synaptic cleft and subsequently to an attenuation of depressive symptoms and elevation in mood. Although long-term studies investigating white matter (WM) alterations after exposure to antidepressant treatment exist, results on the acute effects on the brain’s WM microstructure are lacking.
METHODS: In this interventional longitudinal study, 81 subjects were included (33 patients and 48 healthy controls). All participants underwent diffusion weighted imaging (DWI) on two separate days receiving either citalopram or placebo using a randomized, double-blind, cross-over design. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were calculated within FSL and analysed using tract-based spatial statistics (TBSS).
RESULTS: The repeated measures ANOVA model revealed significant decreases after SSRI administration in MD, AD and RD regardless of the group (p<0.05, FWE-corrected). Results were predominantly evident in frontal WM regions comprising the anterior corona radiata, corpus callosum, external capsule and in distinct areas of the frontal blade. No increases in diffusivity were found and no changes in FA were present.
CONCLUSIONS: Our investigation provides first evidence that fast WM microstructure adaptions within one hour after intravenous SSRI administration precede elevations in mood due to SSRI treatment. These results add a new facet to the complex mode of action of antidepressant therapy. This study was registered at clinicaltrials.gov with the identifier NCT02711215.
PMID:33667309 | DOI:10.1093/ijnp/pyab008
