Featured Finding Figure
Auditory cortex in humans is located on the superior temporal gyrus, where it serves to process auditory sensory input and phonemic elements. In subjects with schizophrenia, the rapid initial phases of transfer and processing of sensory information within the auditory cortex are impaired, and manifest as the reduced ability to discriminate tones and correlated deficits in the recognition of spoken emotion. We have hypothesized that these deficits result, in part, from structural impairments in the feedforward, but not feedback, projections in the auditory cortex. In the current study, we used immunoreactivity for synaptophysin to label presumptive axon terminals in the auditory cortex of subjects with schizophrenia, each paired with an unaffected comparison subject, and quantified their density using a stereologic approach. (A) Synaptophysin-immunoreactive (SY-IR) terminals in a normal comparison subject. Each panel represents a different z-axis depth, in microns, below the cut tissue surface, indicated by the adjacent numbers. (B) SY-IR profiles from the box in the 2.0 µm panel, shown at higher magnification. Labeled puncta were identified by their round appearance, with a diameter of 0.5 to 1.5 µm (red arrowhead). Resolution of individual puncta was aided by using the additional visual information present in the z-axis, ascertained by scrolling the fine focus up and down during the microscopy sessions. For example, neither the SY-IR feature identified by the blue arrowhead, nor the irregularly shaped SY-IR feature identified by the white arrowhead, would meet criteria for quantification in this focal plane. (C) The same SY-IR features indicated by the blue and white arrowheads in (B), but viewed in the focal plane shown in the 1.0 µm panel. The SY-IR profile indicated by the blue arrowhead now is seen to have a distinct punctate appearance with sharp borders. Similarly, the SY-IR feature indicated by the white arrowhead can be resolved into discrete puncta. (D) Consistent with our hypothesis, SY-IR puncta density was significantly reduced by 13.6%within the feedforward pathway, in deep layer 3 of area 41, although SY-IR puncta density in another component of this pathway, deep layer 3 of area 42, was unchanged. SY-IR puncta density was not changed in layer 1 of area 41, a component of the feedback pathway. (E) The reduction in SY-IR puncta density did not appear to be a confound of long-term antipsychotic treatment, as SY-IR puncta densities in the corresponding regions and layers did not differ between monkeys that were antipsychotic naïve (c) or exposed (t) to chronic haloperidol. The reduction in density of presumptive excitatory axon terminals found in the subjects with schizophrenia would be expected to lead to impairments in the spread of activation within the primary auditory cortex after auditory stimuli, and may thus contribute to the observations of impaired auditory function in this disease.
Sweet RA, Bergen SE, Sun Z, Marcsisin MJ, Sampson AR, Lewis DA: Anatomical Evidence of Impaired Feedforward Auditory Processing in Schizophrenia. Biol Psychiatry 61: 854-864, 2007.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
Pittsburgh, Pennsylvania 15213-2593
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