Background
Increased neuronal density in prefrontal, parietal, and temporal white matter of schizophrenia
subjects is thought to reflect disordered neurodevelopment; however, it is not known
if this cellular alteration affects the cingulate cortex and whether similar changes
exist in bipolar disorder.
Method
Eighty-two postmortem specimens (bipolar 15, schizophrenia 22, control 45) were included
in this clinical study. Densities for two neuronal markers, neuron-specific nuclear
protein (NeuN) and neuregulin 1 alpha (NRG), were determined in white matter up to
2.5 mm beneath the anterior cingulate cortex; density of NeuN immunopositive neurons
(NeuN+) was also determined for a subset of cases in prefrontal cortex. Changes during
normal development were monitored in a separate cohort of 14 brains.
Results
Both the schizophrenia and bipolar cohorts demonstrated a twofold increase in NeuN+
density in cingulate white matter; this effect could be attributed to ∼25% of cases
that exceeded the second standard deviation from control subjects. Similar changes
were observed in prefrontal cortex. In contrast density of NRG expressing neurons
was unaltered. Cases with increased NeuN+ densities in two-dimensional (2-D) counts
also showed a pronounced, > fivefold elevation in NeuN+ nuclei per cubic millimeter.
Additionally, the developmental cohort demonstrated a 75% decline in NeuN+ neuronal
density during the first postnatal year but was stable thereafter.
Conclusions
Increased neuronal density in white matter of cingulate cortex in schizophrenia provides
further evidence that this alteration occurs in multiple cortical areas. Similar changes
in some cases with bipolar illness suggest that the two disorders may share a common
underlying defect in late prenatal or early postnatal neurodevelopment.
Key Words
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Article info
Publication history
Published online: June 26, 2009
Accepted:
April 29,
2009
Received in revised form:
April 27,
2009
Received:
December 30,
2008
Footnotes
Authors CMC and YG contributed equally to this work.
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
