We first contrasted gray matter in SCZ vs. NC using an ANCOVA. A widespread distribution of significant gray matter decreases was found in patients compared with healthy volunteers (FWE p<.05, cluster size > 5) (, ). The most robust differences in regional gray matter were observed in the superior and inferior frontal, the medial prefrontal, the insular, left superior temporal, and the inferior parietal cortices, the medial thalamus and the posterior cerebellum. There were also increases in gray matter in SCZ compared with NC in the medial cerebellum, globus pallidus, left inferior temporal cortex, right middle temporal gyrus, left precentral gyrus, left anterior cingulate, and orbitofrontal cortex ().
Summary of the results obtained by voxel-wise wtatistical analysis of the GM Maps of decreases in SCZ and SIB compared with NC. Only the peak voxels are listed. Left is defined as “L” and Right is defined as “R”.
Figure 1 Statistical maps of the entire brain showing gray matter volume reductions in: A. SCZ compared with NC (at a threshold of p<.05 FWE corrected, cluster size > 5), B. SCZ compared to SIB (at a threshold of p<.05 FWE corrected, cluster (more ...)
Table 3 Summary of the results obtained by voxel-wise statistical analysis of the gray matter maps of increases in SCZ compared with NC listed rostal to caudal. Below that are results of the analysis of gray matter increases in SIB compared with NC. Patients (more ...)
The ANCOVA comparing SCZ vs. SIB revealed significant gray matter decreases in the patients when compared to their healthy siblings (FWE p<.05) (, ). These decreases in patients were in the fronto-polar cortex (superior and middle frontal gyri, BA 10), inferior frontal gyrus, right pre- and post-central gyrus, left middle temporal gyrus, right medial parietal cortex, left prestriate cortex, right ventrolateral nucleus of the thalamus and the right ventral cerebellum. In addition, the ANCOVA comparing SCZ vs. SIBnopast revealed similar significant gray matter decreases in the patients, namely in the left and right superior and middle frontal gyri (BA 9 and 10), left inferior frontal gyrus (BA 45), and the right ventrolateral nucleus of the thalamus. Peaks unique to this subgroup with no past psychiatric history were in the left insula, right superior temporal gyrus (BA 22) and right parietal cortex (BA 40) (). The ANCOVA comparing SCZ vs. SIBpast revealed similar frontal cortical regions as the combined group and the no past depression group, with the addition of left and right BA 46, the left middle frontal gyrus (BA 6), the right precentral gyrus (BA 6), the right thalamus, and the right superior temporal gyrus (BA 22) (). In all three analyses the patients had two large clusters of increased gray matter in the cerebellum (bilateral culmen, p<.001 FWE, k=40,690, 28, −53, −38), and the left lateral globus pallidus (lentiform nucleus, p<.000 FWE, k=9,661, −18, −3 −3) compared to the unaffected siblings.
Table 4 Summary of the results obtained by voxel-wise statistical analysis of the gray matter maps of decreases in SCZ compared with SIB, SIBpast, and SIBnopast. Only peak findings that reached our threshold for significance are listed (FWE p<.05, cluster (more ...)
The ANCOVA comparing SIB vs. NC revealed several focal gray matter decreases in the SIB when compared to NC, but these did not survive correction across the whole brain. At an exploratory threshold (p<.001, uncorrected) (), these decreases were in the medial frontal cortex, the right anterior cingulate, the inferior temporal gyrus, the parahippocampal gyrus, right hippocampus, left putamen, and left cerebellum. The ANCOVA comparing SIBpast vs. NC revealed no suprathreshold voxels for increases or decreases, even at an uncorrected threshold at p<.001. The ANCOVA comparing SIBnopast vs. NC resulted in the same clusters listed from the SIB vs. NC analysis above, such that there was no significant contribution of mood disorder history on the gray matter decreases compared with healthy controls. SIBs had increased gray matter compared to NC at an exploratory threshold (p<.001, uncorrected) in the right inferior frontal cortex (BA 45 and BA 9), right parahippocampal gyrus, right inferior frontal gyrus, and right precuneus ().
The masked analysis revealed regions that were commonly decreased in the SCZ and SIB when compared with NC (, ). These were the left medial frontal polar cortex, paracingulate cortex, left inferior frontal gyrus, left insula, and left superior temporal gyrus. The most significant differences lay in the left medial frontal gyrus, left insula, and left superior temporal gyrus. These volumes were extracted as described and plotted in .
Figure 2 Mean differences in regional gray matter volume in regions identified by the masked analysis. The left insula, left medial temporal gyrus, and left superior temporal gyrus (sphere of 2mm around listed coordinate) were decreased in SCZ compared with NC, (more ...)
The ICC calculations within gray matter regions of interest, as well as calculated p-values are listed in . The left hippocampus, right hippocampus, and bilateral hippocampus had significant intra-class correlation coefficients within sib-pairs. The three regions implicated in the masked analysis were not significantly correlated within sib-pairs. In addition, the ICC analysis was not significant within Brodmann's area 17.
Summary of ICC results from ROI analysis of mean gray matter volumes between 116 sibling pairs.