Cingulate gyrus neuroanatomy in schizophrenia subjects and their non-psychotic siblings

Abstract

Background and methods: In vivo neuroimaging studies have provided evidence of decreases in the gray matter volume of the cingulate gyrus in subjects with schizophrenia as compared to healthy controls. To investigate whether these changes might be related to heritable influences, we used high-resolution magnetic resonance imaging and labeled cortical mantle distance mapping to measure gray matter volume, as well as thickness and the area of the gray/white interface, in the anterior and posterior segments of the cingulate gyrus in 28 subjects with schizophrenia and their non-psychotic siblings, and in 38 healthy control subjects and their siblings.

Results: There was a significant effect of group status on posterior cingulate cortex (PCC) gray matter volume (p=0.02). Subjects with schizophrenia and their non-psychotic siblings showed similar reductions of gray matter volume (approximately 10%) in the PCC compared to healthy control subjects and their siblings. In turn, trend level effects of group status were found for thickness (p=0.08) and surface area (p=0.11) of the PCC. In the combined group of schizophrenia subjects and their siblings, a direct correlation was observed between PCC gray matter volume and negative symptoms. However, the reduction in PCC gray matter volume in schizophrenia subjects and their siblings was proportionate to an overall reduction in whole cerebral volume, i.e., the effect of group on the volume of the PCC became non-significant when cerebral volume was included as a covariate (p=0.4). There was no significant effect of group on anterior cingulate cortex volume, thickness, or area.

Conclusions: Our findings suggest that decreases in the gray matter volume of the PCC occur in schizophrenia subjects and their siblings. The presence of such decreases in the non-psychotic siblings of schizophrenia subjects suggests that heritable factors may be involved in the development of cortical abnormalities in schizophrenia.

Figure 1

Outline of Cingulate Gyrus procedure. A. Panel depicts the rough region of interest (yellow) surrounding the cingulate gyrus in a sagittal view. The red line shows the division between ACC and PCC. B. The alternating kernel method was used to segment gray matter (blue intensities), white matter (white intensities), and cerebral spinal fluid (red) in a local region of interest, in coronal view. As the cingulate gyrus follows a “C” shape (in sagittal view), a coronal section sometimes contains a top and bottom region, as depicted here. Here the top region corresponds to a section through the dorsal portion of the PCC, and the bottom region corresponds to the isthmus of the PCC. C. A path following the sulcal boundaries of the cingulate was traced along the surface corresponding to the cingulate gyrus ROI, from which the cingulate subsurface was extracted. The top part of the panel shows the ROI surface with the sulcal boundary path drawn in blue, and the bottom part of the panel shows the extracted cingulate subsurface, which was the portion of the ROI-surface surrounded by the blue path, in sagittal view. D. The cingulate region of interest was created by projecting voxels into the subsurface, shown in a sideways sagittal view.