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

Abstract

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.

The Psychedelic Future of Post-Traumatic Stress Disorder Treatment

“…Aligned with those changes, increased psychological flexibility is likely to attenuate the cognitive and behavioral rigidity that can be associated with depression [ 273 ]. Additionally, reduced functional connectivity between the right amygdala and the vmPFC as well as the vmPFC and the occipital and parietal lobes; changes in the functional connectivity of the vmPFC and mPFC; and decreased brain modularity have all been associated with treatment response in psychedelic-assisted psychotherapy for depression [ 748 ]. The use of serotonergic psychedelics is also associated with prosocial behavior; the ego-dissolution effect is a potential mitigator of common difficulties in social functioning experienced by individuals with depressive disorders [ 747 ].…”

A systematic review of structural and functional magnetic resonance imaging studies on the neurobiology of depressive symptoms in schizophrenia spectrum disorders

“…Neuroimaging methods could enhance our comprehension of the pathophysiological mechanisms linked to depression in SSDs 20 . For instance, in MDD, identifying neuroimaging correlates of antidepressant treatment responses has enabled researchers to gain insights into how antidepressants impact select brain regions, perhaps leading to improved symptom outcomes 21 . Moreover, neuroimaging can serve as a tool to guide nonpharmacological interventions, such as repetitive transcranial magnetic stimulation (rTMS), allowing for more precise and individualized targeting of symptom-related circuits that optimize treatment response 22 – 25 .…”

Polygenic scores of subcortical brain volumes as possible modulators of treatment response in depression

“…The integrity of white matter tracts in the cortico-striatal-limbic systems was also useful in predicting response to treatment (Perlman et al, 2019); these tracts connect the orbitofrontal cortex with subcortical structures, such as the nucleus accumbens, amygdala, caudate nucleus, globus pallidus, putamen, and thalamus (Fettes et al, 2017). The importance of subcortical structures in the modulation of response to medications for depression was also highlighted by functional studies showing that the activity of the amygdala may predict response to psychedelic drugs (Kuburi et al, 2022).…”