Commentary

Glutamatergic dysfunction


 

References

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I read with interest the article by Drs. Kantrowitz and Javitt (“Glutamate: New hope for schizophrenia treatment,” Current Psychiatry, April 2011, p. 68-74) describing the glutamatergic model of schizophrenia. There is extensive evidence that in addition to neurocognitive deficits, schizophrenia is characterized by various neuromuscular abnormalities, including skeletal muscle fiber changes, alterations of alpha-motor neuron excitability, increased motor unit fiber densities, increased branching of terminal motor nerves, and elevated levels of muscular enzymes.1,2 These neuromuscular abnormalities also are found in healthy first-degree relatives of patients with schizophrenia.3 Although the precise cause of these neuromuscular abnormalities has not been elucidated, one possible explanation is that they may be the result of neuronal injury mediated by excitatory amino acids.1 For example, Stevens4 suggested that abnormal sprouting and reinnervation of neurons in schizophrenia might be caused by such injury.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative syndrome involving upper and lower alpha-motor neuron systems. A substantial body of evidence supports the hypothesis that glutamate-mediated excito-toxicity is responsible for the death of motor neurons in ALS.5 Evidence suggests that having schizophrenia may be associated with an increased risk of developing ALS, and this risk might be explained by the toxic effects of excitatory amino acids on neuronal function.1,6 Recently, Stommel et al7 hypothesized that treating schizophrenia could protect against development of ALS, which is of interest because antipsychotics may have direct and indirect effects on modulating glutamate receptor systems.8

Robert H. Howland, MD
Associate Professor of Psychiatry
University of Pittsburgh School of Medicine
Western Psychiatric Institute and Clinic
Pittsburgh, PA

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