Unchanged packing density but altered size of neurofilament immunoreactive neurons in the prefrontal cortex in schizophrenia and major depression

Abstract

Morphometric changes in the general population of Nissl-stained neurons in area 9 of the dorsolateral prefrontal cortex have been reported in major depressive disorder (MDD) and schizophrenia. These alterations include lamina-specific reductions in the packing density of neuronal somata in MDD, increases or reductions in the density of neuronal somata in schizophrenia, and reductions in average size of neuronal somata in both MDD and schizophrenia. These changes are prominent in deep layer III, where pyramidal excitatory neurons establishing cortico-cortical association connections are localized. To test whether deep layer III pyramidal neurons are differentially affected in MDD or schizophrenia, an antibody was used that labels both phosphorylated and non-phosphorylated forms of the 200 kD neurofilament protein (NF200) in pyramidal cells of layer III in area 9. The packing density and somal size of NF200-immunoreactive (IR) pyramidal neurons were measured in area 9 in 13 subjects with nonpsychotic MDD, 11 subjects with schizophrenia and 13 psychiatrically normal controls. Analysis of covariance did not reveal a difference in packing density among groups. However, the mean size of NF200-IR somata was significantly larger in subjects with schizophrenia than in controls. These results indicate that this neuronal subpopulation does not contribute to the smaller average size of neuronal somata in layer III of prefrontal cortical area 9 in schizophrenia or MDD. In addition, the enlarged somal size in schizophrenia as compared to controls suggests that NF200 neurons may contribute differentially to unique cognitive disturbances present in schizophrenia and not in MDD subjects.