Somal size of prefrontal cortical pyramidal neurons in schizophrenia: Differential effects across neuronal subpopulations

Background: Cognitive dysfunction in schizophrenia may be related to morphologic abnormalities of pyramidal neurons in the dorsal prefrontal cortex (dPFC) and the largest pyramidal neurons in deep layer 3 may be most affected. Immunoreactivity (IR) for the nonphosphorylated epitopes of neurofilament protein (NNFP) identifies a subset of large dPFC deep layer 3 pyramidal neurons. We tested the hypotheses that the average size of NNFP-IR neurons is smaller in schizophrenia and that the decrease in size of these neurons is greater than that observed in the general population of deep layer 3 pyramidal neurons. Methods: We estimated the mean somal volume of NNFP-IR neurons in deep layer 3 of 9 in 13 matched pairs of control and schizophrenia subjects and compared the differences in soma! size of NNFP-IR neurons to the differences in size of all deep layer 3 pyramidal neurons identified in Nissl-stained material. Results: In subjects with schizophrenia, the somal volume of NNFP-IR neurons was nonsignificantly decreased by 6.6%, whereas that of the Nissl-stained pyramidal neurons was significantly decreased by 14.2%. Conclusions: These results suggest that the NNFP-IR subpopulation of dPFC pyramidal neurons are not preferentially affected in schizophrenia. Thus, a subpopulation of dPFC deep layer 3 pyramidal neurons, other than those identified by NNFP-IR, may be selectively vulnerable in schizophrenia. (C) 2003 Society of Biological Psychiatry.