Hippocampal and amygdalar local structural differences in elderly patients with schizophrenia

Abstract

Objectives: Morphological abnormalities have been reported for the hippocampi and amygdalae in young schizophrenia patients, but very little is known about the pattern of abnormalities in elderly schizophrenia patients. Here we investigated local structural differences in the hippocampi and amygdalae of elderly schizophrenia patients compared with healthy elderly subjects. We also related these differences to clinical symptom severity.

Design: 20 schizophrenia patients (mean age: 67.4 ± 6.2 years; Mini-Mental State Exam: 22.8 ± 4.4) and 20 healthy elderly subjects (70.3 ± 7.5 years; 29.0 ± 1.1) underwent high resolution magnetic resonance imaging of the brain. The Radial Atrophy Mapping technique was used to reconstruct the 3D shape of the amygdala and the hippocampus. Local differences in tissue reductions were computed between groups and permutation tests were run to correct for multiple comparisons, in statistical maps thresholded at p = 0.05.

Results: Significant tissue reduction was observed bilaterally in the amygdala and hippocampus of schizophrenia patients. The basolateral-ventral-medial amygdalar nucleus showed the greatest involvement, with over 30% local tissue reduction. The centro-medial, cortical, and lateral nuclei were also atrophic in patients. The hippocampus showed significant tissue loss in the medio-caudal and antero-lateral aspects of CA1, and in medial section of its left head (pre- and para-subiculum). In the left amygdala and hippocampus, local tissue volumes were significantly correlated with negative symptoms.

Conclusions: Tissue loss and altered morphology were found in elderly schizophrenia patients. Tissue loss mapped to amygdalo-hippocampal subregions known to have bidirectional and specific connections with frontal cortical and limbic structures and was related to clinical severity.

Keywords: 3D-shape; Elders; amygdala; hippocampus; schizophrenia; volumetric imaging.

Figure 1

(A) Surface of cytoarchitectonic sectors of the hippocampus reconstructed in 3D using an atlas (28) and projected on the surface of the mesh model (B). Local hippocampal differences between 20 elderly schizophrenia subjects and 19 healthy elders, expressed as percent difference and statistical significance (C). P values below maps represent the significance after correction for multiple comparisons (permutation test). Spots from light blue to yellow represent tissue reductions of 10 to 30% in schizophrenia patients respect to healthy elders.

Figure 2

(A) 3D surface reconstruction of amygdalar nuclei by an atlas (28) and projected on the surface of the mesh model (B). Local amygdala differences between 20 elderly schizophrenia subjects and 19 healthy elders, expressed as percent difference and statistical significance (C). P values below maps represent the significance after correction for multiple comparisons (permutation test). Spots from light blue to yellow represent tissue reductions of 10 to 30% in schizophrenia patients respect to healthy elders.

Figure 3

Maps of positive (red range) and negative (green-yellow range) schizophrenia hippocampal and amygdalar local tissue correlation with negative symptoms at the PANSS. P values below maps represent the significance after correction for multiple comparisons (permutation test).