title: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Mainberger
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Bernd
authors.identifier: 0000-0002-9436-1258
authors.initials: B
authors.lastname: Feige
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Maier
authors.forename: Mailies
authors.initials: M
authors.lastname: Wirminghaus
authors.forename: Lotte
authors.initials: L
authors.lastname: Limbach
authors.affiliation: Department of Pediatrics, Technische Universität München, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mall
authors.affiliation: Department of Pediatrics, Technische Universität München, Munich, Germany.
authors.forename: Nicolai H
authors.initials: NH
authors.lastname: Jung
authors.affiliation: Department of Neurology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Reis
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.|Department of Neurology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klöppel
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Normann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Nissen
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D004576:Electromyography; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology*; D009483:Neuropsychological Tests; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult