Full Text (PDF) Selemon/Kleinman/Herman Response Correction (v164,p529) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by BARTZOKIS, G. Articles by ALTSHULER, L. Search for Related Content PubMed Citation Articles by BARTZOKIS, G. Articles by ALTSHULER, L. Gender Schizophrenia Spectrum Disorders Suicide Homicide Conventional Neuroleptics

Reduced Intracortical Myelination in Schizophrenia

To the Editor: Lynn D. Selemon, Ph.D., and colleagues (1) suggested that frontal cortical volume is reduced in schizophrenia. We suggest the possibility that a subtle fixation artifact may offer an alternative and more comprehensive explanation for their results.

Past dogma erroneously suggested that the aging process of normal adulthood is associated with a reduction in cortical neuron number. This conclusion was based on data showing that neuronal density in young adults was higher than in middle-aged to older individuals. The apparent age-related reductions in cortical neuronal density were later shown to be caused by an age-related tissue fixation shrinkage artifact that caused cortices from younger individuals to shrink more than older ones. Unbiased stereological assessments have demonstrated that there is minimal if any neuronal cell loss or cortical thickness decrements before the age of 55 (reviewed in references 2–4).

The excess fixation-related cortical shrinkage of younger brains is likely because of their lower levels of intracortical myelin. Intracortical myelination increases during adulthood to peak in the mid to late fifth decade of life in association with regions such as the frontal and temporal lobes (reviewed in references 3 and 4), and the lipid-rich myelin reduces the amount of dehydration-related cortical shrinkage (5, 6). Thus, the lower the myelin content of any cortex, the more fixation shrinkage is expected.

Genetic, imaging, and cellular evidence for a myelination defect in schizophrenia has been published (reviewed in references 3, 4, and 7). A 22% reduction in frontal lobe cortical oligodendrocyte density has been observed (7). This reduction may itself be an underestimate for the same reasons (excessive shrinkage upon fixation), as discussed.

Therefore, it is possible that the apparent reduction in cortical volume in the frontal lobes of schizophrenics and the associated evidence of "reduced neuropil" in schizophrenia (1) may in large part be due to a myelination deficit of this and other regions that normally continue to myelinate in adulthood (2–4). We suggest that oligodendrocyte and myelin sheath reductions result in a modest loss of cortical neuropil and that this loss is likely further amplified by fixation artifact (5, 6).

Footnotes

Reprints are not available; however, Letters to the Editor can be downloaded at http://ajp.psychiatryonline.org.

References

1. Selemon LD, Kleinman JE, Herman MM, Goldman-Rakic PS: Smaller frontal gray matter volume in postmortem schizophrenic brains. Am J Psychiatry 2002; 159:1983–1991[Abstract/Free Full Text]
2. Bartzokis G, Beckson M, Lu PH, Nuechterlein KH, Edwards N, Mintz J: Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. Arch Gen Psychiatry 2001; 58:461–465[Abstract/Free Full Text]
3. Bartzokis G: Schizophrenia: breakdown in the well-regulated lifelong process of brain development and maturation. Neuropsychopharmacology 2002; 27:672–683[CrossRef][Medline]
4. Bartzokis G, Nuechterlein KH, Lu PH, Gitlin M, Rogers S, Mintz J: Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study. Biol Psychiatry 2003; 53:412–421[CrossRef][Medline]
5. Kreschmann H-J, Tafesse U, Herrmann A: Different volume changes of cerebral cortex and white matter during biological histological preparation. Microsc Acta 1982; 86:13–24[Medline]
6. Ogata J, Feigin I: The relative weight of the gray and white matter of the normal human brain. J Neuropathol Exp Neurol 1973; 32:585–588[Medline]
7. Hof PR, Haroutunian V, Copland C, Davis KL, Buxbaum JD: Molecular and cellular evidence for an oligodendrocyte abnormality in schizophrenia. Neurochem Res 2002; 27:1193–1200[CrossRef][Medline]

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Full Text (PDF) Selemon/Kleinman/Herman Response Correction (v164,p529) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by BARTZOKIS, G. Articles by ALTSHULER, L. Search for Related Content PubMed Citation Articles by BARTZOKIS, G. Articles by ALTSHULER, L. Gender Schizophrenia Spectrum Disorders Suicide Homicide Conventional Neuroleptics

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