BA 41 Deep Layer 3
The density of SP-IR puncta in deep layer 3 of BA 41 was significantly decreased in subjects with schizophrenia in both the primary (F(1,13.3) = 10.16, p = .007) and secondary (F(1,23.3) = 6.10, p = .02) statistical models. The latter did not reveal an association of puncta density with age, gender, PMI, or storage time. Estimated mean (95% C.I.) SP-IR puncta densities derived from the primary model were 0.0276 (0.0240, 0.0313) puncta/μm3 and 0.201 (0.0165, 0.0237) puncta/μm3 in normal comparison subjects and subjects with schizophrenia, respectively, a 27.2% reduction in the subjects with schizophrenia ().
Figure 6 Spinophilin-immunoreactive puncta densities in deep layer 3 of BA 41 (A) and BA 42 (B). In all panels, densities are shown as number of spinophilin-immunoreactive puncta/μm3. Each circle represents a pair with the comparison subject's mean puncta (more ...)
BA 42 Deep Layer 3
The density of SP-IR puncta in deep layer 3 of BA 42 was significantly decreased in subjects with schizophrenia in the primary model (F(1,12.6) = 10.02, p = .008) and nearly so (F(1,23.5) = 4.12, p = .054) in the secondary statistical model. The latter also revealed an association of decreased puncta density with increased PMI (F(1,25) = 5.12, p = .03). Estimated mean (95% C.I.) SP-IR puncta densities derived from the primary model were 0.0302 (0.0269, 0.0334) puncta/μm3 and 0.0235 (0.0203, 0.0267) puncta/μm3 in normal comparison subjects and subjects with schizophrenia, respectively, a 22.2% reduction in the subjects with schizophrenia.
Potential Clinical Confounds
The density of SP-IR puncta did not significantly differ when contrasting subject pairs in which the schizophrenia subject: 1) was on versus off antipsychotic treatment at the time of death (BA 41 t(13) = -.072, p = .48, BA 42 t(13) = -.066, p = .52); 2) did or did not have comorbid alcohol dependence (BA 41 t(13) = .452, p = .66, BA 42 t(13) = 1.02, p = .32); or 3) received a diagnosis of schizophrenia versus a diagnosis of schizoaffective disorder (BA 41 t(13) = -.23, p = .82, BA 42 t(13) =.69, p = .50). Age of onset of schizophrenia (BA 41 r = -.09, p = 0.74, BA 42 r = .02, p = 0.95) and duration of illness (BA 41 r = -.05, p = 0.87, BA 42 r = -.06, p = 0.82) were not significantly correlated with the percent change (relative to the matched control subject) in puncta density in either region. There was, however, a significant association between a history of death by suicide and percent reduction in SP-IR puncta density in both BA 41 and BA 42 (t(13) = 2.92, p = .01, and t(3.8) = 3.33, p = .03, respectively). In BA 41 the mean (SD) percent reduction in SP-IR puncta density for subject pairs in which the subject with schizophrenia had died by suicide was 49.9% (9.4), while for subject pairs in which the subject with schizophrenia had died in other manners it was 10.4% (42.9). The corresponding values in BA 42 were 48.5% (16.7) and 10.5% (21.1). To assess whether the observed reductions in SP-IR density were confined to subjects with death by suicide, we reanalyzed our primary model after excluding these three subject pairs. Evidence of lower SP-IR density was persistent for the remaining 12 pairs in both BA 41 and BA 42 (F(1,10.7) = 4.54, p = .06 and F(1,11.1) = 4.72, p = .05).
Effects of Pyramidal Cell Somal Volume and Axon Terminal Density Reductions
We examined whether SP-IR puncta density was correlated with our prior observations of axon terminal density and pyramidal cell somal volume in the same regions and subjects (). Significant correlations of SP-IR densities and axon terminal densities were seen in both BA 41 and BA 42. In contrast, SP-IR density was not correlated with pyramidal cell somal volume in either region.
Figure 7 Correlations of spinophilin-immunoreactive puncta densities in deep layer 3 of BA41 and BA42 with axon terminal density (A and B) and pyramidal cell somal volume (C and D) in the same locations. Filled circles represent comparison subjects, Squares represent (more ...)
Mean (SD) SP-IR puncta densities were 0.0375 (0.006) puncta/μm3 and 0.0383 (0.012) puncta/μm3 in control animals and in antipsychotic-exposed animals, respectively. The density of SP-IR puncta in deep layer 3 of auditory parabelt did not significantly differ between antipsychotic-exposed and control animals [Mean difference (95% C.I.) -0.0008 (-0.0265, 0.0250), t(3) = -.09, p = .93].