Year: 2021
Type: article
Abstract: 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.
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,340
Funders: National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, Michael Smith Health Research BC, National Institute for Health and Care Research, King's College London, H. Lundbeck A/S, Victoria General Hospital Foundation, Canadian Institutes of Health Research, Medical Research Council, National Institute of Mental Health
Awards: Tools for Human Neuroscience Drug Research 2: THuNDR2, G224075605, MICA: SRC inhibition as a potential target for Parkinson's disease psychosis, The neural mechanisms linking psychotic disorders and the social environment, G5236209695, THE IMPACT OF EARLY ADVERSITY ON TRAJECTORIES OF BRAIN MATURATION AND MENTAL HEALTH IN YOUNG ADOLESCENTS, G5639932287, G6868616705, G7416102250, Tools for Human Neuroscience Drug Research 2: THuNDR2, Investigating Glutamate and Opioid Mechanisms of Antidepressant Response to Ketamine (GO-MARK), G8417216027, NIHR Senior Investigator Award, The neural mechanisms linking psychotic disorders and the social environment
OpenAlex ID: W3162599249