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BDNF-Val66Met-polymorphism impact on cortical plasticity in schizophrenia patients: a proof-of-concept study
Wolfgang Strube1, Michael A Nitsche2, Thomas Wobrock2
1Department 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.
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.
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