Neurotoxicity, Neuroplasticity, and Magnetic Resonance Imaging Morphometry: What is Really Happening in the Schizophrenic Brain? Daniel Weinberger & Robert K. McClure. Archives of General Psychiatry, vol 59, p 553-558, June 2002. [The authors are from the Clinical Brain Disorders Branch of the NIMH]

There is tremendous interest nowadays in establishing a neurodegenerative (aka neurotoxicity) model of schizophrenia. It would fit with the drug company desire to market early medication intervention and even prophylaxis. "Enthusiasm for the notion of neurodegeneration in schizophrenia (and other psychiatric disorders) has outpaced the strength of the evidence." There is no post mortem evidence of degeneration, no loss of neurons, degeneration of neurons, or gliosis. That leaves only two lines of evidence in favor of neurodegeneration 1) apparent clinical progression of certain aspects of the illness, including personality degeneration, dilapidation, and treatment resistance (cognitive functions was noted to remain stable) and 2) MRI studies showing changes in volume measures -- the focus of this article. The problem with MRI studies is that "no 2 studies have found the same pattern of changes" and "in most studies, patients have improved symptomatically while their MRI changes have appeared to progress." Even more puzzling is that the observed volume losses have been of huge magnitudes, more than for known degenerative disorders such as Alzheimer's, far more than can be confirmed in post mortem studies, and far more than can be sustained for long. Shrinkages are about 7% per year and lateral ventricles appear to double in size every 8 to 10 years, at those rates an adolescent patient would have no brain left by the time they turned 60. Yet similar rates of change have been seen in patients in their teens, 20's, 40's and 50's, both in first episode patients and patients with several years of disease. These authors therefore assume that there must be some plasticity to the brain with physiologic volume variation as well as variation caused by environmental factors -- including neuroleptics.