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

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 lon...

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Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2016-05, Vol.41 (6), p.1521-1529
Main Authors: Kuhn, Marion, Mainberger, Florian, Feige, Bernd, Maier, Jonathan G, Wirminghaus, Mailies, Limbach, Lotte, Mall, Volker, Jung, Nicolai H, Reis, Janine, Klöppel, Stefan, Normann, Claus, Nissen, Christoph
Format: Article
Language:English
Subjects:
Adolescent
Adult
Case-Control Studies
Cerebral Cortex - physiopathology
Depressive Disorder, Major - physiopathology
Electromyography
Female
Humans
Hypotheses
Long-Term Potentiation
Male
Mental depression
Middle Aged
Neuronal Plasticity - physiology
Neuropsychological Tests
Original
Psychotherapy
Transcranial Magnetic Stimulation
Young Adult
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Summary: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.
ISSN:0893-133X
1740-634X
DOI:10.1038/npp.2015.310