Encoding, Consolidation, and Renormalization in Depression : Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

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Rantamäki, T & Kohtala, S 2020, ' Encoding, Consolidation, and Renormalization in Depression : Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects ', Pharmacological Reviews, vol. 72, no. 2, pp. 439-465 . https://doi.org/10.1124/pr.119.018697

Title: Encoding, Consolidation, and Renormalization in Depression : Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects
Author: Rantamäki, Tomi; Kohtala, Samuel
Contributor organization: Drug Research Program
Division of Pharmacology and Pharmacotherapy
Laboratory of Neurotherapeutics
Faculty of Pharmacy
SLEEPWELL Research Program
Faculty of Medicine
University of Helsinki
Divisions of Faculty of Pharmacy
Date: 2020-04
Language: eng
Number of pages: 27
Belongs to series: Pharmacological Reviews
ISSN: 0031-6997
DOI: https://doi.org/10.1124/pr.119.018697
URI: http://hdl.handle.net/10138/316273
Abstract: Recent studies have strived to find an association between rapid antidepressant effects and a specific subset of pharmacological targets and molecular pathways. Here, we propose a broader hypothesis of encoding, consolidation, and renormalization in depression (ENCORE-D), which suggests that, fundamentally, rapid and sustained antidepressant effects rely on intrinsic homeostatic mechanisms evoked as a response to the acute pharmacological or physiologic effects triggered by the treatment. We review evidence that supports the notion that various treatments with a rapid onset of action, such as ketamine, electroconvulsive therapy, and sleep deprivation, share the ability to acutely excite cortical networks, which increases synaptic potentiation, alters patterns of functional connectivity, and ameliorates depressive symptoms. We proceed to examine how the initial effects are short-lived and, as such, require both consolidation during wake and maintenance throughout sleep to remain sustained. Here, we incorporate elements from the synaptic homeostasis hypothesis and theorize that the fundamental mechanisms of synaptic plasticity and sleep, particularly the homeostatic emergence of slow-wave electroencephalogram activity and the renormalization of synaptic strength, are at the center of sustained antidepressant effects. We conclude by discussing the various implications of the ENCORE-D hypothesis and offer several considerations for future experimental and clinical research. Significance Statement-Proposed molecular perspectives of rapid antidepressant effects fail to appreciate the temporal distribution of the effects of ketamine on cortical excitation and plasticity as well as the prolonged influence on depressive symptoms. The encoding, consolidation, and renormalization in depression hypothesis proposes that the lasting clinical effects can be best explained by adaptive functional and structural alterations in neural circuitries set in motion in response to the acute pharmacological effects of ketamine (i.e., changes evoked during the engagement of receptor targets such as N-methyl-D-aspartate receptors) or other putative rapid-acting antidepressants. The present hypothesis opens a completely new avenue for conceptualizing and targeting brain mechanisms that are important for antidepressant effects wherein sleep and synaptic homeostasis are at the center stage.
Subject: LONG-TERM POTENTIATION
TREATMENT-RESISTANT DEPRESSION
SLOW-WAVE-SLEEP
GLYCOGEN-SYNTHASE KINASE-3
TRANSCRANIAL MAGNETIC STIMULATION
DORSOLATERAL PREFRONTAL CORTEX
CEREBRAL PROTEIN-SYNTHESIS
DENDRITIC SPINE STABILITY
ANTERIOR CINGULATE CORTEX
NMDA RECEPTOR BLOCKADE
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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