Investigation of motor cortical long-term potentiation-like plasticity in schizophrenia patients: an anodal transcranial direct current stimulation study

Context: Neural and cortical plasticity involves the reorganization of synaptic connections and represent the brain`s ability to reorganize its functions in response to external stimuli. Long-term potentiation is one important mechanism underlying these synaptic changes. Dysfunctional neuronal plasticity is considered to be involved in the pathophysiology of schizophrenia. Objective: To investigate nonfocal motor-cortical plasticity and excitability in recent-onset and multi-episode schizophrenia compared to healthy subjects. Design: Nonfocal cortical plasticity can be induced in the motor cortex of healthy subjects with anodal transcranial direct current stimulation. Animal and human research indicates that these effects are related to glutamate-dependent long-term-potentiation. Transcranial direct current stimulation-induced plasticity was monitored by transcranial magnetic stimulation-generated motor evoked potentials. Healthy controls were compared to schizophrenia patients and the latter group was divided into recent-onset and multi-episode patients. Setting: All patient were recruited from in- and outpatient units from the Department of Psychiatry and Psychotherapy (University of Goettingen). Healthy subjects were recruited from the same geographical area. Main Outcome Measure: It was hypothesized that patients with schizophrenia would display a disturbed long-term-potential-like plasticity compared to healthy controls and that these alterations would be related to the disease course. The main outcome measure was change in motor evoked potentials after stimulation across study groups. Results: Multi-episode schizophrenia patients showed significantly reduced long-term-potential-like plasticity compared to recent-onset schizophrenia patients and healthy controls. All schizophrenia patients demonstrated reduced cortical inhibition. Conclusion: These results indicate that the long-term-potential-like plasticity deficit in chronically ill schizophrenia patients is related to the disease course. Disturbances of N-methyl-D-Aspartate, gamma-aminobutyric acid and dopamine receptors may account for this plasticity deficit. LTP-like plasticity deficits might be related to disturbed information processing in schizophrenia patients.2015-09-2