Dysfunctional neural plasticity in patients with schizophrenia.
BACKGROUND
Neural plasticity in the human cortex involves a reorganization of synaptic connections in an effort to adapt to a changing environment. In schizophrenia, dysfunctional neural plasticity has been proposed as a key pathophysiological mechanism.


OBJECTIVE
To evaluate neural plasticity in unmedicated and medicated patients with schizophrenia compared with healthy subjects.


METHODS
Neural plasticity can be evaluated from the motor cortex in healthy subjects using transcranial magnetic stimulation through a paradigm known as use-dependent plasticity. This paradigm involves several steps: (1) measuring the spontaneous direction of transcranial magnetic stimulation-induced thumb movements; (2) training subjects to practice thumb movements opposite to this baseline direction for 30 minutes; and (3) measuring the direction of transcranial magnetic stimulation-induced thumb movement after training. Previous experiments have shown that in healthy subjects, posttraining transcranial magnetic stimulation-induced movements occur in a vector commensurate with the practiced movements, which may be associated with time-limited reorganization of motor circuits.


METHODS
All of the participants were recruited and evaluated at the Centre for Addiction and Mental Health.


METHODS
Fourteen medicated and 6 unmedicated patients with schizophrenia and 20 healthy subjects were recruited.


METHODS
It was anticipated that patients with schizophrenia would demonstrate attenuated motor reorganization in the direction of training.


RESULTS
Both medicated and unmedicated patients with schizophrenia demonstrated significantly reduced motor reorganization compared with healthy subjects.


CONCLUSIONS
It is possible that in schizophrenia, these deficits in neural plasticity are related to disturbances of gamma-aminobutyric acid, N-methyl-D-aspartate neurotransmission, or dopamine that may potentially account for the aberrant motor performance of these patients.
Daskalakis
Zafiris J
ZJ
Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. jeff_daskalakis@camh.net
Christensen
Bruce K
BK
Fitzgerald
Paul B
PB
Chen
Robert
R
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003710:Demography; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009949:Orientation; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D013663:Teaching / Q000379:methods; D050781:Transcranial Magnetic Stimulation
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D018079:Receptors, GABA