Department of Neuroscience, Imaging, and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, Italy; Institute for Advanced Biomedical Technologies (ITAB), "G. d'Annunzio" University, Chieti-Pescara, Italy. Electronic address: ssensi@uci.edu.
3 papers in the library · 51 citations · publishing 2023-2024
LSD selectively alters the functional connectivity between specific thalamic nuclei and sensory and associative cortical areas. Using structural and resting-state functional MRI in healthy volunteers under acute LSD administration, researchers found increased coupling of the ventral complex, pulvinar, and non-specific thalamic nuclei with somatosensory and auditory cortices, as well as with associative cortex regions rich in serotonin 2A receptors. At subcortical levels, LSD increased connectivity among these thalamic nuclei but decreased striatal-thalamic connectivity. These nucleus-specific changes help explain LSD's modulation of subcortical-cortical circuits and associated behavioral effects.
LSD alters brain functional connectivity and local signal amplitude in opposite directions depending on the type of serotonin receptor involved. In healthy volunteers, LSD increased activity and connectivity in cortical regions of the default mode and attention networks, which have high densities of 5-HT2A receptors; these changes correlated with visual hallucinations. Conversely, LSD decreased activity and connectivity in limbic areas rich in 5-HT1A receptors. The spatial patterns of these functional changes overlapped with the distribution of the two serotonin receptor subtypes, suggesting distinct receptor-mediated mechanisms underlie LSD's reorganization of brain networks.
In patients with treatment-resistant depression, combining vortioxetine with esketamine nasal spray reduces depressive symptoms as effectively as the standard combination of an SSRI or SNRI with esketamine. The vortioxetine combination also showed a larger reduction in emotional blunting after three months and had fewer treatment-emergent side effects. These findings come from a post-hoc analysis of twenty patients, ten in each group. The authors suggest the vortioxetine-plus-esketamine regimen may be a valuable alternative, but they call for larger randomized controlled trials to confirm the results.