Anatomical evidence of impaired feedforward auditory processing in schizophrenia.
BACKGROUND
Somal volumes of pyramidal cells are reduced within feedforward but not feedback circuits in areas 41 and 42 of the auditory cortex of subjects with schizophrenia. Because neuronal somal volume depends on both the number of axonal terminations onto and furnished by the neuron, we hypothesized that axon terminal densities are reduced in feedforward but not feedback auditory pathways in subjects with schizophrenia.


METHODS
We used stereologic methods to quantify the density of a marker of axon terminals, synaptophysin-immunoreactive (SY-IR) puncta, in areas 41 and 42 of 15 subjects with schizophrenia and matched normal comparison subjects. The effect of long-term haloperidol exposure on density of SY-IR puncta was similarly evaluated in nonhuman primates.


RESULTS
Synaptophysin-immunoreactive puncta density was 13.6% lower in deep layer 3 of area 41 in the schizophrenia subjects but was not changed in layer 1 of area 41 or in deep layer 3 of area 42. Density of SY-IR puncta did not differ between haloperidol-exposed and control monkeys.


CONCLUSIONS
Reduction of SY-IR puncta density is selective for feedforward circuits within primary auditory cortex of subjects with schizophrenia. This deficit may contribute to impairments in auditory sensory processing in this disorder.
Sweet
Robert A
RA
Department of Psychiatry, University of Pittsburgh, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania 15213, USA. sweetra@upmc.edu
Bergen
Sarah E
SE
Sun
Zhuoxin
Z
Marcsisin
Michael J
MJ
Sampson
Allan R
AR
Lewis
David A
DA
D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001306:Auditory Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008252:Macaca fascicularis / Q000033:anatomy & histology; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D015999:Multivariate Analysis; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology*; D013238:Stereotaxic Techniques; D016708:Synaptophysin / Q000378:metabolism
D014150:Antipsychotic Agents; D016708:Synaptophysin; D006220:Haloperidol