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  • Title: Indices of cortical plasticity after therapeutic sleep deprivation in patients with major depressive disorder.
    Author: Kuhn M, Maier JG, Wolf E, Mainberger F, Feige B, Maywald S, Bredl A, Michel M, Sendelbach N, Normann C, Klöppel S, Eckert A, Riemann D, Nissen C.
    Journal: J Affect Disord; 2020 Dec 01; 277():425-435. PubMed ID: 32866801.
    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.
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