BDNF-Val66Met-polymorphism impact on cortical plasticity in schizophrenia patients: a proof-of-concept study

Wolfgang Strube; Michael A Nitsche; Thomas Wobrock; Tilmann Bunse; Bettina Rein; Maximiliane Herrmann; Andrea Schmitt; Vanessa Nieratschker; Stephanie H Witt; Marcella Rietschel; Peter Falkai; Alkomiet Hasan

doi:10.1093/ijnp/pyu040

BDNF-Val66Met-polymorphism impact on cortical plasticity in schizophrenia patients: a proof-of-concept study

Int J Neuropsychopharmacol. 2014 Oct 31;18(4):pyu040. doi: 10.1093/ijnp/pyu040.

Affiliations

¹ 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.
² 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).

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.

Keywords: brain-derived neurotrophic factor; motor-cortical plasticity; schizophrenia; transcranial direct current stimulation; transcranial magnetic stimulation.

MeSH terms

Adult
Brain-Derived Neurotrophic Factor / genetics*
Evoked Potentials, Motor / genetics
Female
Genotyping Techniques
Heterozygote
Humans
Male
Motor Cortex / physiopathology*
Neuronal Plasticity / physiology*
Polymorphism, Genetic*
Psychiatric Status Rating Scales
Schizophrenia / drug therapy
Schizophrenia / genetics*
Schizophrenia / physiopathology*
Transcranial Direct Current Stimulation / methods

Substances

Brain-Derived Neurotrophic Factor
BDNF protein, human