Contrasting the amygdala activity and functional connectivity profile between antidepressant-free participants with major depressive disorder and healthy controls: A systematic review of comparative fMRI studies.

Functional neuroimaging research suggests that the amygdala is implicated in the pathophysiology of major depressive disorder (MDD). This systematic review aimed to identify consistently reported amygdala activity and functional connectivity (FC) abnormalities in antidepressant-free participants with MDD as compared to healthy controls at baseline (i.e., before treatment initiation or experimental manipulation). A search for relevant published studies and registered clinical trials was conducted through OVID (MEDLINE, PsycINFO, and Embase) and ClinicalTrials.gov with an end date of March 7th, 2022. Fifty published studies and two registered clinical trials were included in this review. Participants with MDD frequently exhibited amygdala hyperactivity in response to negative stimuli, abnormal event-related amygdala-anterior cingulate cortex (ACC) FC, and abnormal resting-state amygdala FC with the insula and the prefrontal, temporal, and parietal cortices. Decreased resting-state FC was consistently found between the amygdala and the orbitofrontal cortex, striatum, cerebellum, and middle/inferior frontal gyri. Due to the limited number of studies examining resting-state amygdala activity and FC with specific subregions of interest, including those within the ACC, further investigation is warranted.

Neuroimaging Correlates of Treatment Response with Psychedelics in Major Depressive Disorder: A Systematic Review.

Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42 articles were screened. Six published studies and one conference abstract were included. Five ongoing trials were included from subjective outcomesTrials.gov. Our search covered several psychedelics, though included studies were specific to psilocybin, ayahuasca, and lysergic acid diethylamide. Three psilocybin studies noted amygdala activity and functional connectivity (FC) alterations that correlated with treatment response. Two psilocybin studies reported that FC changes in the medial and ventromedial prefrontal cortices correlated with treatment response. Two trials from a single study reported global decreases in brain network modularity which correlated with antidepressant response. One ayahuasca study reported increased activity in the limbic regions following treatment. Preliminary evidence suggests that the default mode and limbic networks may be a target for future research on the neural mechanisms of psychedelics. More data is required to corroborate these initial findings as the evidence summarized in this review is based on four datasets.