Synaptic Elimination and the Treatment of Prodromal Symptoms in Schizophrenia

As the investigator who proposed that schizophrenia is a neurodevelopmental disorder caused by errors in adolescent synaptic pruning,¹ I wish to comment on the article by Drs McGlashan and Woods,²“Early Antecedents and Detection of Schizophrenia” in the March 2011 issue of Psychiatric Times. When I proposed the synaptic pruning model, I noted that schizophrenia might result from the elimination of “too many, too few, or the wrong synapses” during adolescence, and that we had no basis for choosing among these possibilities. Any of these errors could produce the impaired integration of brain systems that Bleuler³ considered the cardinal defect in schizophrenia.

Some years ago, McGlashan and Hoffman⁴ created a computer simulation to illustrate how excessive pruning might produce schizophrenic symptoms. However, one could devise other simulations in which the elimination of too few or of the wrong synapses would give rise to these symptoms. Unfortunately, we still have no basis for choosing among the 3 types of error in synaptic elimination originally envisioned.

Although McGlashan and Woods² do not make this error, readers of the current psychiatric literature might be led to conclude that the structural MRI findings of increased or accelerated cortical thinning in schizophrenia demonstrate abnormally increased synaptic elimination. However, MRI-measured cortical thickness is quite unlikely to be determined by the density of synapses, which are ultramicroscopic. Indeed, the anatomical basis of this MRI change is unknown and it may even be nonneuronal.⁵

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