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Current Psychiatry Reports
Published in: Current Psychiatry Reports 5/2019

01-05-2019 | Sleep Disorders (P Gehrman, Section Editor)

An Integrated Model of Slow-Wave Activity and Neuroplasticity Impairments in Major Depressive Disorder

Authors: Jennifer R. Goldschmied, Philip Gehrman

Published in: Current Psychiatry Reports | Issue 5/2019

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Abstract

Purpose of Review

In this review, we aim to integrate the most recent research highlighting alterations in sleep slow-wave activity (SWA), and impairments in neuroplasticity in major depressive disorder (MDD) into a novel model of disorder maintenance.

Recent Findings

Sleep homeostasis has been shown to be impaired in MDD, with a subset of individuals also demonstrating impaired SWA. SWA is considered a marker of the homeostatic regulation of sleep, and is implicated in the downscaling of synaptic strength in the context of maintaining homeostatic plasticity. Individuals with MDD have been shown to exhibit impairments in both neural plasticity such as loss of dendritic branching, and synaptic plasticity such as decreased long-term potentiation-dependent learning and memory.

Summary

Alterations in the homeostatic regulation of sleep, SWA, and synaptic plasticity in MDD suggest an underlying impairment in the modulation of synaptic strength. One candidate mechanism for this impairment is AMPA receptor trafficking.
Literature
1.
Baglioni C, Nanovska S, Regen W, Spiegelhalder K, Feige B, Nissen C, et al. Sleep and mental disorders: a meta-analysis of polysomnographic research. Psychol Bull. 2016;142(9):969–90.CrossRef
2.
Tsuno N, Besset A, Ritchie K. Sleep and depression. J Clin Psychiatry. 2005;66(10):1254–69.CrossRef
3.
Armitage R, Hoffmann RF. Sleep EEG, depression and gender. Sleep Med Rev. 2001;5(3):237–46.CrossRef
4.
Benca RM, Obermeyer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders: a meta-analysis. Arch Gen Psychiatry. 1992;49(8):651–68.CrossRef
5.
Swanson LM, Hoffmann R, Armitage R. Sleep macroarchitecture in depression: sex differences. Open Sleep J. 2010;3:12–8.CrossRef
6.
Armitage R, Hoffmann R, Trivedi M, Rush AJ. Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls. Psychiatry Res. 2000;95(3):201–13.CrossRef
7.
Goldschmied JR, Cheng P, Armitage R, Deldin PJ. Examining the effects of sleep delay on depressed males and females and healthy controls. J Sleep Res. 2014;23(6):664–72.CrossRef
8.
Frey S, Birchler-Pedross A, Hofstetter M, Brunner P, Götz T, Münch M, et al. Young women with major depression live on higher homeostatic sleep pressure than healthy controls. Chronobiol Int. 2012;29(3):278–94.CrossRef
9.
Duman RS, Voleti B. Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci. 2012;35(1):47–56.CrossRef
10.
•• Tononi G, Cirelli C. Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull. 2003;62(2):143–50 This comprehensive theoretical review posits that the function of sleep is to facilitate the downscaling of synaptic strength in order to maintain synaptic homeostasis. CrossRef
11.
Borbely AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1(3):195–204.PubMed
12.
Borbély AA, Baumann F, Brandeis D, Strauch I, Lehmann D. Sleep deprivation: effect on sleep stages and EEG power density in man. Electroencephalogr Clin Neurophysiol. 1981;51(5):483–93.CrossRef
13.
Werth E, Dijk DJ, Achermann P, Borbely AA. Dynamics of the sleep EEG after an early evening nap: experimental data and simulations. Am J Phys. 1996;271(3 Pt 2):R501–10.
14.
Borbely AA, Wirz-Justice A. Sleep, sleep deprivation and depression. A hypothesis derived from a model of sleep regulation. Hum Neurobiol. 1982;1(3):205–10.PubMed
15.
Boland EM, Rao H, Dinges DF, Smith RV, Goel N, Detre JA, et al. Meta-analysis of the antidepressant effects of acute sleep deprivation. J Clin Psychiatry. 2017;78(8):e1020–34.CrossRef
16.
Wirz-Justice A, Van den Hoofdakker RH. Sleep deprivation in depression: what do we know, where do we go? Biol Psychiatry. 1999;46(4):445–53.CrossRef
17.
Gillin JC, Buchsbaum M, Wu J, Clark C, Bunney W. Sleep deprivation as a model experimental antidepressant treatment: findings from functional brain imaging. Depress Anxiety. 2001;14(1):37–49.CrossRef
18.
Goldstein MR, Plante DT, Hulse BK, Sarasso S, Landsness EC, Tononi G, et al. Overnight changes in waking auditory evoked potential amplitude reflect altered sleep homeostasis in major depression. Acta Psychiatr Scand. 2012;125(6):468–77.CrossRef
19.
Plante DT, Goldstein MR, Landsness EC, Riedner BA, Guokas JJ, Wanger T, et al. Altered overnight modulation of spontaneous waking EEG reflects altered sleep homeostasis in major depressive disorder: a high-density EEG investigation. J Affect Disord. 2013;150(3):1167–73.CrossRef
20.
Kupfer DJ, Frank E, McEachran AB, Grochocinski VJ. Delta sleep ratio: a biological correlate of early recurrence in unipolar affective disorder. Arch Gen Psychiatry. 1990;47(12):1100–5.CrossRef
21.
Lotrich FE, Germain A. Decreased delta sleep ratio and elevated alpha power predict vulnerability to depression during interferon-alpha treatment. Acta Neuropsychiatr. 2015;27(01):14–24.CrossRef
22.
Thase ME, Fasiczka AL, Berman SR, Simons AD, Reynolds CF. Electroencephalographic sleep profiles before and after cognitive behavior therapy of depression. Arch Gen Psychiatry. 1998;55(2):138–44.CrossRef
23.
• Goldschmied JR, Cheng P, Hoffmann R, Boland EM, Deldin PJ, Armitage R. Effects of slow-wave activity on mood disturbance in major depressive disorder. Psychol Med. 2018;1–7. This study demonstrates that a slower rate of SWA dissipation is associated with increased mood disturbance in depression, providing evidence that the mechanism responsible for the modulation of SWA is associated with mood regulation in depression.
24.
Liu ZW, Faraguna U, Cirelli C, Tononi G, Gao XB. Direct evidence for wake-related increases and sleep-related decreases in synaptic strength in rodent cortex. J Neurosci. 2010;30(25):8671–5.CrossRef
25.
Diering GH, Nirujogi RS, Roth RH, Worley PF, Pandey A, Huganir RL. Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science. 2017;355(6324):511–5.CrossRef
26.
• de Vivo L, Bellesi M, Marshall W, Bushong EA, Ellisman MH, Tononi G, et al. Ultrastructural evidence for synaptic scaling across the wake/sleep cycle. Science. 2017;355(6324):507–10 This study provides evidence for the synaptic homeostasis hypothesis by objectively demonstrating structural changes associated with the downscaling of synapses following sleep. CrossRef
27.
•• Wolf E, Kuhn M, Normann C, Mainberger F, Maier JG, Maywald S, et al. Synaptic plasticity model of therapeutic sleep deprivation in major depression. Sleep Med Rev. 2016;30:53–62 This theoretical paper reviews the synaptic plasticity model of depression and the synaptic homeostasis hypothesis and introduces an integrative model that posits that depression is characterized by a deficiency in synaptic strength and sleep deprivation results in antidepressant effects by normalizing this deficiency.CrossRef
28.
Wu JC, Bunney WE. The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Am J Psychiatry. 1990;147(1):14–21.CrossRef
29.
Landsness EC, Goldstein MR, Peterson MJ, Tononi G, Benca RM. Antidepressant effects of selective slow wave sleep deprivation in major depression: a high-density EEG investigation. J Psychiatr Res. 2011;45(8):1019–26.CrossRef
30.
• Cheng P, Goldschmied J, Casement M, Kim HS, Hoffmann R, Armitage R, et al. Reduction in delta activity predicted improved negative affect in major depressive disorder. Psychiatry Res. 2015;228(3):715–8 This study demonstrates that following an experimental slow-wave disruption paradigm, a reduction in SWA was associated with a decrease in self-reported negative affect in MDD, providing early evidence that SWA may be depressogenic. CrossRef
31.
Beersma DG, Van den Hoofdakker RH. Can non-REM sleep be depressogenic? J Affect Disord. 1992;24(2):101–8.CrossRef
32.
McIntyre RS, Cha DS, Soczynska JK, Woldeyohannes HO, Gallaugher LA, Kudlow P, et al. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety. 2013;30(6):515–27.CrossRef
33.
Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008;7(5):426–37.CrossRef
34.
Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology. 2008;33(1):88–109.CrossRef
35.
Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997;386(6627):824–7.CrossRef
36.
Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Jurjus GJ, Meltzer HY, et al. Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry. 2004;56(9):640–50.CrossRef
37.
Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59(12):1116–27.CrossRef
38.
Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008;64(6):527–32.CrossRef
39.
• Player MJ, Taylor JL, Weickert CS, Alonzo A, Sachdev P, Martin D, et al. Neuroplasticity in depressed individuals compared with healthy controls. Neuropsychopharmacology. 2013;38(11):2101–8 This is one of the first studies to objectively demonstrate neuroplasticity impairments in MDD. Paired associative stimulation, a TMS-based approach, provides an in-vivo index of associative neuroplasticity. CrossRef
40.
•• Marsden W. Synaptic plasticity in depression: molecular, cellular and functional correlates. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;43:168–84 A clear and concise review of the neurobiological features associated with synaptic plasticity, and of the pre-clinical and clinical evidence that suggests that depression is characterized by alterations to these features. CrossRef
41.
Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22(3):238–49.CrossRef
42.
Normann C, Schmitz D, Fürmaier A, Döing C, Bach M. Long-term plasticity of visually evoked potentials in humans is altered in major depression. Biol Psychiatry. 2007;62(5):373–80.CrossRef
43.
Popoli M, Gennarelli M, Racagni G. Modulation of synaptic plasticity by stress and antidepressants. Bipolar Disord. 2002;4(3):166–82.CrossRef
44.
Duncan WC, Zarate CA. Ketamine, sleep, and depression: current status and new questions. Curr Psychiatry Rep. 2013;15(9):394.CrossRef
45.
Alt A, Nisenbaum ES, Bleakman D, Witkin JM. A role for AMPA receptors in mood disorders. Biochem Pharmacol. 2006;71(9):1273–88.CrossRef
46.
• Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533(7604):481–6 Critical study that demonstrates that the mechanism of action of ketamine may not be mediated directly via NMDA receptor antagonism, but rather via increased AMPA receptor throughput. CrossRef
47.
•• Freudenberg F, Celikel T, Reif A. The role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in depression: central mediators of pathophysiology and antidepressant activity? Neurosci Biobehav Rev. 2015;52:193–206 A comprehensive review of the clinical and pre-clinical evidence that suggests that AMPA receptors are altered in MDD, and that the modulation of AMPA receptors may be involved with the mechanism of action of antidepressant drugs. CrossRef
48.
Murthy VN. Synaptic plasticity: step-wise strengthening. Curr Biol. 1998;8(18):R650–3.CrossRef
49.
Koizumi T, Tani H, Nakajima S, Nagai N, Suzuki T, Mimura M, et al. T108. AMPA receptor subunit expression and receptor binding in patients with major depressive disorder: a systematic review of postmortem studies. Biol Psychiatry. 2018;83(9):S170.CrossRef
50.
Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O’shea DJ, et al. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature. 2011;477(7363):171–8.CrossRef
51.
Groch S, Wilhelm I, Diekelmann S, Born J. The role of REM sleep in the processing of emotional memories: evidence from behavior and event-related potentials. Neurobiol Learn Mem. 2013;99:1–9.CrossRef
52.
Allen NJ, Barres BA. Signaling between glia and neurons: focus on synaptic plasticity. Curr Opin Neurobiol. 2005;15(5):542–8.CrossRef
53.
Havekes R, Vecsey CG, Abel T. The impact of sleep deprivation on neuronal and glial signaling pathways important for memory and synaptic plasticity. Cell Signal. 2012;24(6):1251–60.CrossRef
54.
Cotter D, Mackay D, Landau S, Kerwin R, Everall I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry. 2001;58(6):545–53.CrossRef
55.
Bowley MP, Drevets WC, Öngür D, Price JL. Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry. 2002;52(5):404–12.CrossRef
56.
Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999;45(9):1085–98.CrossRef
57.
Ngo HV, Martinetz T, Born J, Mölle M. Auditory closed-loop stimulation of the sleep slow oscillation enhances memory. Neuron. 2013;78(3):545–53.CrossRef
58.
Besedovsky L, Ngo HV, Dimitrov S, Gassenmaier C, Lehmann R, Born J. Auditory closed-loop stimulation of EEG slow oscillations strengthens sleep and signs of its immune-supportive function. Nat Commun. 2017;8(1):1984.CrossRef
Metadata
Title
An Integrated Model of Slow-Wave Activity and Neuroplasticity Impairments in Major Depressive Disorder
Authors
Jennifer R. Goldschmied
Philip Gehrman
Publication date
01-05-2019
Publisher
Springer US
Published in
Current Psychiatry Reports / Issue 5/2019
Print ISSN: 1523-3812
Electronic ISSN: 1535-1645
DOI
https://doi.org/10.1007/s11920-019-1013-4

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