Pyramidal cell size reduction in schizophrenia: Evidence for involvement of auditory feedforward circuits

Background: Subjects with schizophrenia have decreased gray matter volume of auditory cortex in structural imaging studies and exhibit deficits in auditory sensory processing that might reflect impairments of feedforward and/or feedback circuits within the auditory cortex. Recently, we reported that one component of these circuits, pyramidal cells in deep layer 3 of the auditory association cortex (area 42), has reduced mean somal volume in subjects with schizophrenia. To discriminate between involvement of feedforward and feedback circuit components, we examined pyramidal cell somal volume in layer 3 of primary auditory cortex (feedforward) and layer 5 of auditory association cortex (feedback). Methods. We estimated somal volumes of pyramidal neurons in deep layer 3 of area 41 and layer 5 of area 42 in subjects with schizophrenia (area 41, n = 16; area 42, n = 18), each of whom was matched to one normal comparison subject for gender, age, and postmortem interval. Results. In deep layer 3 of area 41, mean pyramidal cell somal volume was significantly reduced, by 10.4%. No significant reduction was present in layer 5 of area 42. Conclusions: Pyramidal cell somal volume is reduced in layer 3 of area 41 and area 42, but not in layer 5 of area 42, of subjects with schizophrenia. This pattern of abnormalities is consistent with impairments of auditory feedforward projection neurons.