0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Reduced Intracortical Myelination in Schizophrenia
GEORGE BARTZOKIS, M.D.; LORI ALTSHULER, M.D.
Am J Psychiatry 2005;162:1229-a-1230. doi:10.1176/appi.ajp.162.6.1229-a
An erratum to this article has been published | view the erratum

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 24).

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 (24). 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).

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

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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
Bartzokis G: Schizophrenia: breakdown in the well-regulated lifelong process of brain development and maturation. Neuropsychopharmacology  2002; 27:672–683
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
+

References

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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
Bartzokis G: Schizophrenia: breakdown in the well-regulated lifelong process of brain development and maturation. Neuropsychopharmacology  2002; 27:672–683
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 17

Related Content
Books
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 24.  >
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 24.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 5.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 6.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 6.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
APA Guidelines
PubMed Articles