title: BDNF-Val66Met-polymorphism impact on cortical plasticity in schizophrenia patients: a proof-of-concept study.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients.
  
  
  METHODS
  Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied.
  
  
  RESULTS
  Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS.
  
  
  CONCLUSIONS
  These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory intracortical interneuron-networks, cortical plasticity, and the BDNF-Val66Met-polymorphism. Further replication and validation need to be dedicated to this question to confirm this relationship.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel). wolfgang.strube@med.uni-muenchen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Strube
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nitsche
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Thomas
authors.initials: T
authors.lastname: Wobrock
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bunse
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Bettina
authors.initials: B
authors.lastname: Rein
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Maximiliane
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Andrea
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nieratschker
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D019054:Evoked Potentials, Motor / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D065908:Transcranial Direct Current Stimulation / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: brain-derived neurotrophic factor; motor-cortical plasticity; schizophrenia; transcranial direct current stimulation; transcranial magnetic stimulation