title: Impaired long-term depression in schizophrenia: a cathodal tDCS pilot study.
abstract: BACKGROUND
  Neural plasticity involves the reorganization of synaptic connections and represents the ability of the brain to adjust its function in response to challenge. Disturbed cortical plasticity has been linked to the pathophysiology of schizophrenia, with indirect evidence for disturbed plasticity in the disease state having been provided by postmortem studies and various animal models. However, glutamate-dependent long-term depression (LTD)-like cortical plasticity has not yet been investigated.
  
  
  OBJECTIVE
  To investigate LTD-like cortical plasticity after transcranial direct current stimulation (tDCS) in schizophrenia patients.
  
  
  METHODS
  Using excitability-diminishing cathodal tDCS, we performed the first in vivo assessment of glutamate-dependent LTD-like cortical plasticity in 21 schizophrenia patients and 21 matched healthy control subjects. To reveal the physiologic basis of the hypothesized plasticity deficits, we tested different inhibitory and excitatory neuronal circuits with transcranial magnetic stimulation (TMS).
  
  
  RESULTS
  Cathodal tDCS failed to reduce motor-evoked potential amplitudes in schizophrenia patients, indicating abolished LTD-like plasticity. Furthermore, schizophrenia patients had a prolonged GABA(B)-dependent cortical silent period (CSP) at baseline and tDCS failed to modulate the duration of CSP in the patient group. Finally, schizophrenia patients presented an elevated resting-motor threshold at baseline in comparison to healthy controls.
  
  
  CONCLUSIONS
  The pattern of our results provides evidence for a specific plasticity deficit in schizophrenia patients, which might be associated with a hyperglutamatergic state. These findings may reflect a reduced signal-to-noise ratio and a disturbed filter function in schizophrenia patients. An increase of GABA(B)-activity may be a compensatory mechanism to dysfunctional LTD-like plasticity in schizophrenia.
authors.affiliation: Department of Psychiatry and Psychotherapy, Georg-August University, Goettingen, Germany. ahasan@gwdg.de
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nitsche
authors.forename: Maximiliane
authors.initials: M
authors.lastname: Herrmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider-Axmann
authors.forename: Louise
authors.initials: L
authors.lastname: Marshall
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.forename: Thomas
authors.initials: T
authors.lastname: Wobrock
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000503:physiopathology*; D004558:Electric Stimulation; D004566:Electrodes; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology; D010865:Pilot Projects; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation
chemical_list: D014150:Antipsychotic Agents