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Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies.

Authors
  • Tonon, André C1, 2
  • Pilz, Luísa K1, 2
  • Markus, Regina P3
  • Hidalgo, Maria Paz1, 2
  • Elisabetsky, Elaine4
  • 1 Laboratório de Cronobiologia e Sono, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. , (Brazil)
  • 2 Graduate Program in Psychiatry and Behavioral Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. , (Brazil)
  • 3 Laboratório de Cronofarmacologia, Departamento de Fisiologia, Instituto de Biociência, Universidade de São Paulo, São Paulo, Brazil. , (Brazil)
  • 4 Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. , (Brazil)
Type
Published Article
Journal
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Publication Date
Jan 01, 2021
Volume
12
Pages
638981–638981
Identifiers
DOI: 10.3389/fpsyt.2021.638981
PMID: 33897495
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Daily rhythm of melatonin synchronizes the body to the light/dark environmental cycle. Several hypotheses have been raised to understand the intersections between melatonin and depression, in which changes in rest-activity and sleep patterns are prominent. This review describes key experimental and clinical evidence that link melatonin with the etiopathology and symptomatology of depressive states, its role in the follow up of therapeutic response to antidepressants, as well as the clinical evidence of melatonin as MDD treatment. Melatonin, as an internal temporal cue contributing to circadian organization and best studied in the context of circadian misalignment, is also implicated in neuroplasticity. The monoaminergic systems that underly MDD and melatonin production overlap. In addition, the urinary metabolite 6-sulfatoxymelatonin (aMT6) has been proposed as biomarker for antidepressant responders, by revealing whether the blockage of noradrenaline uptake has taken place within 24 h from the first antidepressant dose. Even though animal models show benefits from melatonin supplementation on depressive-like behavior, clinical evidence is inconsistent vis-à-vis prophylactic or therapeutic benefits of melatonin or melatonin agonists in depression. We argue that the study of melatonin in MDD or other psychiatric disorders must take into account the specificities of melatonin as an integrating molecule, inextricably linked to entrainment, metabolism, immunity, neurotransmission, and cell homeostasis. Copyright © 2021 Tonon, Pilz, Markus, Hidalgo and Elisabetsky.

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