Neuroleptic Medication & Gray Matter

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Abstract

Both in vivo and post-mortem investigations have demonstrated smaller volumes of the whole brain and of certain brain regions in individuals with schizophrenia. It is unclear to what degree such smaller volumes are due to the illness or to the effects of antipsychotic medication treatment. Indeed, we recently reported that chronic exposure of macaque monkeys to haloperidol or olanzapine, at doses producing plasma levels in the therapeutic range in schizophrenia subjects, was associated with significantly smaller total brain weight and volume, including an 11.8–15.2% smaller gray matter volume in the left parietal lobe. Consequently, in this study we sought to determine whether these smaller volumes were associated with lower numbers of the gray matter's constituent cellular elements. The use of point counting and Cavalieri's principle on Nissl-stained sections confirmed a 14.6% smaller gray matter volume in the left parietal lobe from antipsychotic-exposed monkeys. Use of the optical fractionator method to estimate the number of each cell type in the gray matter revealed a significant 14.2% lower glial cell number with a concomitant 10.2% higher neuron density. The numbers of neurons and endothelial cells did not differ between groups. Together, the findings of smaller gray matter volume, lower glial cell number, and higher neuron density without a difference in total neuron number in antipsychotic-exposed monkeys parallel the results of post-mortem schizophrenia studies, and raise the possibility that such observations in schizophrenia subjects might be due, at least in part, to antipsychotic medication effects.

Source: Effect of Chronic Exposure to Antipsychotic Medication on Cell Numbers in the Parietal Cortex of Macaque Monkeys

Psychiatrist, Loren Mosher, raised this point many years ago.

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As for the abnormalities that researchers have found with brain scans, Mosher thinks the antischizophrenic medication accounts for much of this. He says, "The Germans, who invented neuropathology, looked at the brains of thousands of schizophrenics before there were any neuroleptics. And they were never able to find anything. They never reported increased ventricular volume, which at postmortem you can measure quite easily. And they also never reported any specific cellular pathology, and they studied many, many, many brains." He adds that "there are a whole lot of people who don't have schizophrenia and also have enlarged ventricles. And there are people who have other psychiatric conditions who have enlarged ventricles, and there are a number of known causes of enlarged ventricles that are not schizophrenia. So, yes, there is a statistical difference, but it is not specific."

"On the other hand," Mosher continues, "there are studies that have shown that people treated with neuroleptics have changes in brain structure that are at least associated with drug treatment, dosage, and duration -- and have been shown to increase over time as drugs are given." He cites one "horrific study" of children between the ages of 10 and 15 in which the researchers measured the volumes of the kids' cortexes. "The cortex is what you think with, the part on the outside," Mosher explains. Over time, "They watched the cortical volume of these young people decline, while the cortical volume of the nonschizophrenic controls was expanding because they were adolescents and still growing." The researcher concluded that their schizophrenia had caused the decrease in the subjects. "And yet every single one was taking neuroleptic drugs," Mosher says.

Source: Still Crazy After All These Years


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Ugh, now that made me downright sick.
Definitely gotta make more research on this when I recover (heh, heh)