State-Dependent Partial Occlusion of Cortical LTP-Like Plasticity in Major Depression

Abstract

The synaptic plasticity hypothesis of major depressive disorder (MDD) posits that alterations in synaptic plasticity represent a final common pathway underlying the clinical symptoms of the disorder. This study tested the hypotheses that patients with MDD show an attenuation of cortical synaptic long-term potentiation (LTP)-like plasticity in comparison with healthy controls, and that this attenuation recovers after remission. Cortical synaptic LTP-like plasticity was measured using a transcranial magnetic stimulation protocol, ie, paired associative stimulation (PAS), in 27 in-patients with MDD according to ICD-10 criteria and 27 sex-and age-matched healthy controls. The amplitude of motor-evoked potentials was measured before and after PAS. Patients were assessed during the acute episode and at follow-up to determine the state-or trait-character of LTP-like changes. LTP-like plasticity, the PAS-induced increase in motor-evoked potential amplitudes, was significantly attenuated in patients with an acute episode of MDD compared with healthy controls. Patients with remission showed a restoration of synaptic plasticity, whereas the deficits persisted in patients without remission, indicative for a state-character of impaired LTP-like plasticity. The results provide first evidence for a state-dependent partial occlusion of cortical LTP-like plasticity in MDD. This further identifies impaired LTP-like plasticity as a potential pathomechanism and treatment target of the disorder.

Cortical Plasticity in Depression

“…More recently, an investigation using a PAS protocol in patients with MDD further supported this hypothesis by showing that cortical LTP-like plasticity was significantly decreased in a state-dependent manner in a group of 27 patients who suffered an acute episode of MDD. Interestingly, this study clearly showed that LTP-like plasticity was restored after remission (Kuhn et al., 2016). Finally, after facilitatory PAS, changes in cortical excitability were linked to associative LTP.…”

“…The articles reviewed here provide neurophysiological evidence for altered cortical excitability (Maeda et al., 2000; Fitzgerald et al., 2004; Levinson et al., 2010; Spampinato et al., 2013; Concerto et al., 2013; Croarkin et al., 2013; Veronezi et al., 2016) and synaptic plasticity (Chroni et al., 2008; Bajwa et al., 2008; Spampinato et al., 2013; Croarkin et al., 2013; Player et al., 2013; Kuhn et al., 2016) in MDD. These data confirm the findings of previous investigations that have used different approaches (Debener et al., 2000; Normann et al., 2007; Teyler and Cavus, 2007; Salustri et al., 2007; Nissen et al., 2010).…”

Microglial-driven changes in synaptic plasticity: A possible role in major depressive disorder

“…In particular, studies of cortical excitability and by extension neuronal plasticity in MDD, have reported consistent evidence for changes in LTP-like plasticity in patients with depression. Using a paired associative stimulation protocol, with transcranial stimulations, one study has identified impaired LTP-like plasticity in MDD patients who possess reduced motor evoked potential amplitudes, when compared with healthy controls (Kuhn et al, 2016). This finding was particularly interesting, as these reductions in motor evoked potential amplitudes were restored after MDD patients had entered remission (Kuhn et al, 2016).…”

Targeting Arousal and Sleep through Noninvasive Brain Stimulation to Improve Mental Health

“…Scientifically, sleep deprivation presents a unique paradigm to study rapid mechanisms of antidepressant response and relapse, which are most likely different from those of today's standard treatments. We recently proposed a new framework of mechanisms [44] which integrates two prominent lines of research on MDD and sleep, the synaptic plasticity hypothesis of MDD [45,46] and the synaptic homeostasis hypothesis of sleep-wake regulation [47]. The figure depicts the proposed interplay between the time course of net synaptic strength (homeostatic plasticity; solid and dotted lines) and the inducibility of synaptic LTP (associative plasticity; red window).…”