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Review
. 2022 Aug 2:6:24705470221115342.
doi: 10.1177/24705470221115342. eCollection 2022 Jan-Dec.

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

Sarah Kuburi  1 , Anne-Marie Di Passa  1 , Vanessa K Tassone  1 , Raesham Mahmood  2 , Aleksandra Lalovic  3   4 , Karim S Ladha  4   5   6 , Katharine Dunlop  1   3   7   8 , Sakina Rizvi  3   4 , Ilya Demchenko  1 , Venkat Bhat  1   2   3   4
Affiliations
Review

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

Sarah Kuburi et al. Chronic Stress (Thousand Oaks). .

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.

Keywords: LSD; ayahuasca; depression; neural correlates; psilocybin; psychedelics; systematic review; treatment-resistant depression.

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Conflict of interest statement

Declaration of Conflicting Interests: SK, AD, VKT, RM, AL, SR, and ID declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. KSL is supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto (Toronto, Canada). KD is supported by an Academic Scholar Award from the University of Toronto, Department of Psychiatry. VB is supported by an Academic Scholar Award from the University of Toronto Department of Psychiatry and has received research support from the Canadian Institutes of Health Research, Brain & Behavior Foundation, Ministry of Health Innovation Funds, Royal College of Physicians and Surgeons of Canada, Department of National Defence (Canada), and an investigator-initiated trial from Roche Canada.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram of published studies and registered trials screened and evaluated for eligibility.
Figure 2.
Figure 2.
Type of psychedelic intervention examined in the published studies and conference abstract.
Figure 3.
Figure 3.
Published studies by the per-protocol sample size for each study. Note: Carhart–Harris et al (2017) has two different sample sizes for their ASL and RSFC sample sizes. Doss et al (2021) has four different sample sizes for their RSFC, ACC, left hippocampus and right hippocampus analyses. Daws et al (2022) has two different sample sizes for their psilocybin open-label trial and double-blind RCT.
See this image and copyright information in PMC

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