Indices of cortical plasticity after therapeutic sleep deprivation in patients with major depressive disorder

Marion Kuhn; Jonathan G Maier; Elias Wolf; Florian Mainberger; Bernd Feige; Sarah Maywald; Aliza Bredl; Maike Michel; Nicola Sendelbach; Claus Normann; Stefan Klöppel; Anne Eckert; Dieter Riemann; Christoph Nissen

doi:10.1016/j.jad.2020.08.052

Indices of cortical plasticity after therapeutic sleep deprivation in patients with major depressive disorder

J Affect Disord. 2020 Dec 1:277:425-435. doi: 10.1016/j.jad.2020.08.052. Epub 2020 Aug 27.

Authors

Affiliations

¹ Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
² Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
³ University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
⁴ Neurobiology Lab for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland; Psychiatric University Clinics, University of Basel, Basel, Switzerland.
⁵ Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland. Electronic address: christoph.nissen@upd.ch.

PMID: 32866801
DOI: 10.1016/j.jad.2020.08.052

Abstract

Background: Therapeutic sleep deprivation (SD) presents a unique paradigm to study the neurobiology of major depressive disorder (MDD). However, the rapid antidepressant mechanism, which differs from today's slow first-line treatments, is not sufficiently understood. We recently integrated two prominent hypotheses of MDD and sleep, the synaptic plasticity hypothesis of MDD and the synaptic homeostasis hypothesis of sleep-wake regulation, into a synaptic plasticity model of therapeutic SD in MDD. Here, we further tested this model positing that homeostatically elevating net synaptic strength through therapeutic SD shifts the initially deficient inducibility of associative synaptic long-term potentiation (LTP)-like plasticity in patients with MDD into a more favorable window of associative plasticity.

Methods: We used paired associative stimulation (PAS), a transcranial magnetic stimulation protocol (TMS), to quantify cortical LTP-like plasticity after one night of therapeutic sleep deprivation in 28 patients with MDD.

Results: We demonstrate a significantly different inducibility of associative plasticity in clinical responders to therapeutic SD (> 50% improvement on the 6-item Hamilton-Rating-Scale for Depression, n=13) compared to non-responders (n=15), which was driven by a long-term depression (LTD)-like response in SD-non-responders. Indices of global net synaptic strength (wake EEG theta activity, intracortical inhibition and BDNF serum levels) were increased after SD in both groups, with responders showing a generally lower intracortical inhibition than non-responders.

Limitations: Repetitive assessments prior to and after treatment would be needed to further determine potential mechanisms.

Conclusion: After a night of therapeutic SD, clinical responders show a significantly higher inducibility of associative LTP-like plasticity than non-responders.

Keywords: Major depressive disorder; Sleep deprivation; Synaptic homeostasis hypothesis; Transcranial magnetic stimulation; neural plasticity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Depressive Disorder, Major* / therapy
Evoked Potentials, Motor
Humans
Long-Term Potentiation
Neuronal Plasticity
Sleep Deprivation
Transcranial Magnetic Stimulation