Fornix integrity and hippocampal volume in male schizophrenic patients

Abstract

Background: The hippocampus has been shown to be abnormal in schizophrenia. The fornix is one of the main fiber tracts connecting the hippocampus with other brain regions. Few studies have evaluated the fornix in schizophrenia, however. A focus on fornix abnormalities and their association with hippocampal abnormalities might figure importantly in our understanding of the pathophysiology of schizophrenia.

Methods: Line-scan diffusion tensor imaging (DTI) was used to evaluate diffusion in the fornix in 24 male patients with chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy (FA) and mean diffusivity (D(m)), which are indices sensitive to white-matter integrity, were generated to quantify diffusion within the fornix. We used high spatial resolution magnetic resonance imaging (MRI) to measure hippocampal volume.

Results: FA and cross-sectional area of the fornix were significantly reduced in patients compared with control subjects. D(m) was significantly increased, whereas hippocampal volume was bilaterally reduced in patients. Reduced hippocampal volume was correlated with increased mean D(m) and reduced cross-sectional area of the fornix for patients. Patients also showed a significant correlation between reduced scores on neuropsychologic measures of declarative-episodic memory and reduced hippocampal volumes.

Conclusions: These findings demonstrate a disruption in fornix integrity in patients with schizophrenia.

Figure 1

(A) An illustration showing anisotropic diffusion. In directionally well-organized tissue, such as the white-matter fiber bundles, diffusion along one direction is greater than the others (i.e., λ₁>>λ₂>λ₃). λ1: the largest eigenvalue, which corresponds to the length of the long radial of the ellipsoid; λ₂: the second eigenvalue; λ₃: the smallest eigenvalue; e₁: the eigenvector with the largest eigenvalue; e₂: the eigenvector with the second eigenvalue; e₃: the eigenvector with the smallest eigenvalue. (B) An illustration showing the x-y-z coordinate system that we used. Images are FA maps. x: in-plane horizontal axis (left-right), y: in-plane vertical axis (superior-inferior), z: out-of-plane axis (anterior-posterior).

Figure 2

Fractional anisotropy map, out-of-plane principal diffusion component map, and color-coded map. Upper row: the selected slice. Lower row: the slice just anterior to the selected slice. The boundary of fornix is shown in the out-of-plane principal diffusion component maps and the color-coded maps. In out-of-plane principal diffusion component map, high-intensity corresponds to the fiber tract perpendicular to the plane, and the fornix is easy to differentiate. Two angle maps were merged in this color-coded map to make it more intuitively understandable to the reader. One is a map for the angle between the first eigenvector and the sagittal plane. The other is a map for the angle between the first eigenvector and the axial plane. The color table shows these two angular values of each color. Red color means the first eigenvector closely perpendicular to the coronal plane. Green color means the eigenvector with medial-lateral direction. Green color in the superior part of each color-coded image corresponds to the corpus callosum. Blue color means the eigenvector with superior–inferior direction. Blue color in the inferior part of both sides corresponds to the internal capsule. Blue color in the delineated fornix of the slice just anterior to the selected slice indicates that the fornix is descending inferiorly in this slice. CB, cingulum bundle; CC, corpus callosum; IC, internal capsule.

Figure 3

Scattergrams of fractional anisotropy, D_m, cross-sectional area of the fornix, and relative volume of left and right hippocampus. Mean values are indicated by horizontal bars. SZ, schiophrenia group; NC, normal control group.

Figure 4

Fractional anisotropy map of a schizophrenic patient (SZ, left) and control subject (NC, right). Red color area with a white outline shows the delineated fornix.

Figure 5

Scattergrams between D_m and absolute volume of left and right hippocampus between cross-sectional area of the fornix in patients with schizophrenia. Pearson's Product–Moment correlation coefficients were used for testing statistical significance, and a least squares line is also shown.

Figure 6

Scattergrams between absolute volume of left and right hippocampus and general memory index scores of Wechsler Memory Scale—3rd edition (WMS-III) in patients with schizophrenia. Spearman's rho was used for testing statistical significance; we also plotted a least squares line for the convenience of the reader.