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. 2022 Dec 12;25(12):1003-1013.
doi: 10.1093/ijnp/pyac049.

Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker

Anne Weigand  1 , Matti Gärtner  1   2 , Milan Scheidegger  3 , Patrik O Wyss  4 , Anke Henning  5 , Erich Seifritz  3 , Anna Stippl  2 , Ana Herrera-Melendez  2 , Malek Bajbouj  2 , Sabine Aust  2 , Simone Grimm  1   2   3
Affiliations

Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker

Anne Weigand et al. Int J Neuropsychopharmacol. .

Abstract

Background: Growing evidence underscores the utility of ketamine as an effective and rapid-acting treatment option for major depressive disorder (MDD). However, clinical outcomes vary between patients. Predicting successful response may enable personalized treatment decisions and increase clinical efficacy.

Methods: We here explored the potential of pregenual anterior cingulate cortex (pgACC) activity to predict antidepressant effects of ketamine in relation to ketamine-induced changes in glutamatergic metabolism. Prior to a single i.v. infusion of ketamine, 24 patients with MDD underwent functional magnetic resonance imaging during an emotional picture-viewing task and magnetic resonance spectroscopy. Changes in depressive symptoms were evaluated using the Beck Depression Inventory measured 24 hours pre- and post-intervention. A subsample of 17 patients underwent a follow-up magnetic resonance spectroscopy scan.

Results: Antidepressant efficacy of ketamine was predicted by pgACC activity during emotional stimulation. In addition, pgACC activity was associated with glutamate increase 24 hours after the ketamine infusion, which was in turn related to better clinical outcome.

Conclusions: Our results add to the growing literature implicating a key role of the pgACC in mediating antidepressant effects and highlighting its potential as a multimodal neuroimaging biomarker of early treatment response to ketamine.

Keywords: antidepressant effects; ketamine; multimodal neuroimaging biomarker; pgACC; pregenual anterior cingulate cortex.

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Figures

Figure 1.
Figure 1.
T1 weighted image of 1 exemplary patient. Color overlays represent segmentation results for grey matter (red), white matter (blue), and cerebrospinal fluid (green). In addition, the voxel placement is shown in yellow (figure created with MRIcron, Version 2.9.2019).
Figure 2.
Figure 2.
(A) Representative spectroscopy data with PRESS localization (TE = 80 milliseconds) and LCModel fitting for the first and second time point. (left): The measured data (blue), the fitted spectrum (red) and the baseline (orange) are shown. (right): The fitted signal contribution of glutamate (Glu) is shown as envelope for the first and second time point. (B) Representative 1-dimensional projections of the 2D JPRESS data and ProFit2 fitting for the first and second time point. Left: The measured data (blue), the fitted spectrum (red), and the baseline (orange) are shown for the first and second time point. Right: The 1-dimensional projection of the fitted signal contribution of Glu is shown as envelope for the first and second timepoint.
Figure 3.
Figure 3.
Representative 2-dimensional JPRESS data: the acquired spectrum (1), the fitted spectrum (2) and the fit error (residuum, 3) are shown including the signal contributions of glutamate (4).
Figure 4.
Figure 4.
Prediction of clinical improvement (percent change in the Beck Depression Inventory [BDI] score) based on pregenual anterior cingulate cortex (pgACC) activity during emotional stimulation.
See this image and copyright information in PMC

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References

    1. Abdallah CG, Averill LA, Krystal JH (2015) Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Ann N Y Acad Sci 1344:66–77. - PMC - PubMed
    1. Abdallah CG, Averill LA, Collins KA, Geha P, Schwartz J, Averill C, DeWilde KE, Wong E, Anticevic A, Tang CY, Iosifescu DV, Charney DS, Murrough JW (2017a) Ketamine treatment and global brain connectivity in major depression. Neuropsychopharmacology 42:1210–1219. - PMC - PubMed
    1. Abdallah CG, Hannestad J, Mason GF, Holmes SE, DellaGioia N, Sanacora G, Jiang L, Matuskey D, Satodiya R, Gasparini F, Lin X, Javitch J, Planeta B, Nabulsi N, Carson RE, Esterlis I (2017b) Metabotropic glutamate receptor 5 and glutamate involvement in major depressive disorder: a multimodal imaging study. Biol Psychiatry Cogn Neurosci Neuroimaging 2:449–456. - PMC - PubMed
    1. Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GM, Purohit P, de Graaf RA, Esterlis I, Juchem C (2018) The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 43:2154–2160. - PMC - PubMed
    1. Alexander L, Jelen LA, Mehta MA, Young AH (2021) The anterior cingulate cortex as a key locus of ketamine’s antidepressant action. Neurosci Biobehav Rev 127:531–554. - PubMed

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