title: Synaptic plasticity model of therapeutic sleep deprivation in major depression.
abstract: Therapeutic sleep deprivation (SD) is a rapid acting treatment for major depressive disorder (MDD). Within hours, SD leads to a dramatic decrease in depressive symptoms in 50-60% of patients with MDD. Scientifically, therapeutic SD presents a unique paradigm to study the neurobiology of MDD. Yet, up to now, the neurobiological basis of the antidepressant effect, which is most likely different from today's first-line treatments, is not sufficiently understood. This article puts the idea forward that sleep/wake-dependent shifts in synaptic plasticity, i.e., the neural basis of adaptive network function and behavior, represent a critical mechanism of therapeutic SD in MDD. Particularly, this article centers on two major hypotheses of MDD and sleep, the synaptic plasticity hypothesis of MDD and the synaptic homeostasis hypothesis of sleep-wake regulation, and on how they can be integrated into a novel synaptic plasticity model of therapeutic SD in MDD. As a major component, the model proposes that therapeutic SD, by homeostatically enhancing cortical synaptic strength, shifts the initially deficient inducibility of associative synaptic long-term potentiation (LTP) in patients with MDD in a more favorable window of associative plasticity. Research on the molecular effects of SD in animals and humans, including observations in the neurotrophic, adenosinergic, monoaminergic, and glutamatergic system, provides some support for the hypothesis of associative synaptic plasticity facilitation after therapeutic SD in MDD. The model proposes a novel framework for a mechanism of action of therapeutic SD that can be further tested in humans based on non-invasive indices and in animals based on direct studies of synaptic plasticity. Further determining the mechanisms of action of SD might contribute to the development of novel fast acting treatments for MDD, one of the major health problems worldwide.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Normann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Mainberger
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Maier
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maywald
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Aliza
authors.initials: A
authors.lastname: Bredl
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klöppel
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: van Calker
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Riemann
authors.affiliation: Department of Psychology, University of Surrey, United Kingdom.
authors.forename: Annette
authors.initials: A
authors.lastname: Sterr
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany. Electronic address: christoph.nissen@uniklinik-freiburg.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Nissen
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy*; D006801:Humans; D009473:Neuronal Plasticity; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000503:physiopathology*; D014851:Wakefulness / Q000502:physiology
keywords: LTP; Major depressive disorder; Synaptic homeostasis; Synaptic plasticity; Therapeutic sleep deprivation