Somal Size of Immunolabeled Pyramidal Cells in the Prefrontal Cortex of Subjects with Schizophrenia
Received 27 May 2005; received in revised form 12 October 2005; accepted 22 October 2005. published online 06 February 2006.
Background
Although the somal volume of Nissl-stained deep layer 3 pyramidal cells is reduced in prefrontal cortex area 9 of subjects with schizophrenia, the subset of large pyramidal cells immunoreactive (IR) for nonphosphorylated neurofilament protein (NNFP) is not. Consequently, we hypothesized that the somal volume of another subset of pyramidal cells immunoreactive for neuronal calcium binding protein-1 (Necab-1) is significantly reduced in schizophrenia.
Methods
We labeled Necab-1-IR pyramidal neurons using immunoperoxidase techniques and estimated the mean somal volume in deep layer 3 of area 9 in 13 matched pairs of control and schizophrenic subjects. Identical studies were conducted for pyramidal neurons immunoreactive for neuronal nuclear protein (Neu-N), which is present in all neurons.
Results
In subjects with schizophrenia, neither the mean somal volume of Necab-1-IR pyramidal neurons nor of Neu-N-IR pyramidal neurons was significantly different from control subjects. In addition, the mean somal volume of Neu-N-IR cells was larger than that of Nissl-stained cells in both subject groups, and the magnitude of this difference was greater for the subjects with schizophrenia.
Conclusions
These findings suggest that immunoperoxidase techniques are associated with an overestimation of the volume of labeled neurons. This confound appears to interact with disease state, and thus obscures differences between diagnostic groups.
aDepartment of Neuroscience, University of Pittsburgh, Pennsylvania
bDepartment of Psychiatry, University of Pittsburgh, Pennsylvania
cDepartment of Statistics, University of Pittsburgh, Pennsylvania
Address reprint requests to David A. Lewis, M.D., Department of Psychiatry, University of Pittsburgh, 3811 O’Hara Street, W1651 BST, Pittsburgh, PA 15213
ABSTRACT