Reduction of Synaptophysin Immunoreactivity in the Prefrontal Cortex of Subjects With Schizophrenia: Regional and Diagnostic Specificity

doi:10.1001/archpsyc.1997.01830220065010

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Vol. 54 No. 10, October 1997

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Reduction of Synaptophysin Immunoreactivity in the Prefrontal Cortex of Subjects With Schizophrenia

Regional and Diagnostic Specificity

Leisa A. Glantz, MS; David A. Lewis, MD

Arch Gen Psychiatry. 1997;54(10):943-952.

Abstract

Background
Multiple lines of evidence indicate that the prefrontal cortexis a site of dysfunction in schizophrenia. However, the apparentabsence of gross structural abnormalities in this area suggeststhat the pathophysiological characteristics of schizophreniamay involve more subtle disturbances in prefrontal corticalcircuitry, such as alterations in synaptic connectivity andtransmission. In this study, immunoreactivity for synaptophysin,an integral membrane protein of small synaptic vesicles, wasused to assess the integrity of cortical synaptic circuitryin schizophrenia.

Methods
Using immunocytochemical techniques and adjusted optical densitymeasurements, we examined synaptophysin immunoreactivity inprefrontal cortical areas 9 and 46 and in area 17. (the primaryvisual cortex) from 10 pairs of case subjects with schizophreniaand control subjects matched on a pairwise basis for age, sex,race, and postmortem interval, and in 5 matched pairs of nonschizophrenicpsychiatric case subjects and normal control subjects.

Results
Compared with levels found in matched control subjects, synaptophysinimmunoreactivity in areas 46 and 9 was significantly decreased(P<.001 and P<.008, respectively) across all corticallayers in the case subjects with schizophrenia. In contrast,no differences were observed in area 17. In addition, levelsof synaptophysin immunoreactivity in areas 46, 9, and 17 didnot differ between 5 nonschizophrenic psychiatric case subjectsand their matched controls, suggesting that decreased synaptophysinlevels in the prefrontal cortex of patients with schizophreniamay be specific to that disorder.

Conclusions
Additional studies are required to determine if the decreasein levels of synaptophysin immunoreactivity is caused by a decreasein the number or size of presynaptic terminals, a decrease inthe number of synaptic vesicles per terminal, or a decreasein the expression of synaptophysin. However, all of these potentialexplanations are consistent with a disturbance in synaptic transmissionin the prefrontal cortex of patients with schizophrenia.

Author Affiliations

From the Departments of Neuroscience (Ms Glantz and Dr Lewis) and Psychiatry (Dr Lewis), University of Pittsburgh, Pittsburgh, Pa.

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