The anterior cingulate cortex as a key locus of ketamine's antidepressant action

TY - JOUR

T1 - The anterior cingulate cortex as a key locus of ketamine's antidepressant action

AU - Alexander, Laith

AU - Jelen, Luke A

AU - Mehta, Mitul A

AU - Young, Allan H

N1 - Funding Information: Mitul Mehta: Employed by King’s College London. Grant funding (past 3 years): Takeda , Johnson & Johnson , Lundbeck , Wellcome Trust ( 212952/Z/18/Z ; 200102/Z/15/Z ), MRC ( MR/R005931/1 ; MR/R005885/1 ; MR/S003444/1 ), NIHR ( CRF-2016-10023 ). Funding Information: This report represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London . The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Dr Laith Alexander is an Academic Foundation Doctor at Guy’s and St Thomas’ NHS Foundation Trust. Dr Luke A Jelen is a Medical Research Council (MRC) Clinical Research Training Fellow (MR/T028084/1). The authors thank Min Lee for assistance with the figures in the manuscript. Funding Information: Mitul Mehta: Employed by King's College London. Grant funding (past 3 years): Takeda, Johnson & Johnson, Lundbeck, Wellcome Trust (212952/Z/18/Z; 200102/Z/15/Z), MRC (MR/R005931/1; MR/R005885/1; MR/S003444/1), NIHR (CRF-2016-10023).Allan Young: Employed by King's College London; Honorary Consultant SLaM (NHS UK). Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK). No shareholdings in pharmaceutical companies.This report represents independent research funded by the National Institute for Health Research (NIHR)Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Dr Laith Alexander is an Academic Foundation Doctor at Guy's and St Thomas? NHS Foundation Trust. Dr Luke A Jelen is a Medical Research Council (MRC) Clinical Research Training Fellow (MR/T028084/1). The authors thank Min Lee for assistance with the figures in the manuscript. Funding Information: Allan Young: Employed by King’s College London; Honorary Consultant SLaM (NHS UK). Grant funding (past and present): NIMH (USA) ; CIHR (Canada) ; NARSAD (USA) ; Stanley Medical Research Institute (USA) ; MRC (UK) ; Wellcome Trust (UK) ; Royal College of Physicians (Edin) ; BMA (UK) ; UBC-VGH Foundation (Canada) ; WEDC (Canada) ; CCS Depression Research Fund (Canada ); MSFHR (Canada) ; NIHR (UK) . Janssen (UK) . No shareholdings in pharmaceutical companies. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/8

Y1 - 2021/8

N2 - The subdivisions of the anterior cingulate cortex (ACC) - including subgenual, perigenual and dorsal zones - are implicated in the etiology, pathogenesis and treatment of major depression. We review an emerging body of evidence which suggests that changes in ACC activity are critically important in mediating the antidepressant effects of ketamine, the prototypical member of an emerging class of rapidly acting antidepressants. Infusions of ketamine induce acute (over minutes) and post-acute (over hours to days) modulations in subgenual and perigenual activity, and importantly, these changes can correlate with antidepressant efficacy. The subgenual and dorsal zones of the ACC have been specifically implicated in ketamine's anti-anhedonic effects. We emphasize the synergistic relationship between neuroimaging studies in humans and brain manipulations in animals to understand the causal relationship between changes in brain activity and therapeutic efficacy. We conclude with circuit-based perspectives on ketamine's action: first, related to ACC function in a central network mediating affective pain, and second, related to its role as the anterior node of the default mode network.

AB - The subdivisions of the anterior cingulate cortex (ACC) - including subgenual, perigenual and dorsal zones - are implicated in the etiology, pathogenesis and treatment of major depression. We review an emerging body of evidence which suggests that changes in ACC activity are critically important in mediating the antidepressant effects of ketamine, the prototypical member of an emerging class of rapidly acting antidepressants. Infusions of ketamine induce acute (over minutes) and post-acute (over hours to days) modulations in subgenual and perigenual activity, and importantly, these changes can correlate with antidepressant efficacy. The subgenual and dorsal zones of the ACC have been specifically implicated in ketamine's anti-anhedonic effects. We emphasize the synergistic relationship between neuroimaging studies in humans and brain manipulations in animals to understand the causal relationship between changes in brain activity and therapeutic efficacy. We conclude with circuit-based perspectives on ketamine's action: first, related to ACC function in a central network mediating affective pain, and second, related to its role as the anterior node of the default mode network.

UR - http://www.scopus.com/inward/record.url?scp=85107270972&partnerID=8YFLogxK

U2 - 10.1016/j.neubiorev.2021.05.003

DO - 10.1016/j.neubiorev.2021.05.003

M3 - Review article

C2 - 33984391

SN - 0149-7634

VL - 127

SP - 531

EP - 554

JO - Neuroscience and Biobehavioral Reviews

JF - Neuroscience and Biobehavioral Reviews

ER -