Elsevier

Biological Psychiatry

Volume 64, Issue 12, 15 December 2008, Pages 1060-1068
Biological Psychiatry

Archival Report
Progressive Deformation of Deep Brain Nuclei and Hippocampal-Amygdala Formation in Schizophrenia

https://doi.org/10.1016/j.biopsych.2008.08.007Get rights and content

Background

Progressive decreases in cortical gray matter volume have been reported in schizophrenia. However, studies of progressive change in deep brain nuclei and hippocampal-amygdala formation have not yielded consistent findings.

Methods

Two high-resolution, T1-weighted magnetic resonance images were collected 2 years apart in 56 schizophrenia and 62 control subjects. Large-deformation high-dimensional brain mapping was used to generate surfaces for deep brain nuclei and hippocampal-amygdala formation at baseline and follow-up. Repeated-measures analysis of variance was used to test for longitudinal changes in volume and shape.

Results

The pattern of progressive changes in the deep brain nuclei and hippocampal-amygdala formation in schizophrenia and control subjects was variable. Of the structures that receive direct projections from the cortex, the thalamus, caudate nucleus, nucleus accumbens, and hippocampus showed changes specific to subjects with schizophrenia, and changes in the amygdala and putamen were similar in both groups. Although different at baseline, no progressive change was observed in the globus pallidus, which does not receive direct projections from the cortex.

Conclusions

These findings suggest that the disease process of schizophrenia is associated with progressive effects on brain structure and that brain structures that receive direct, excitatory connections from the cortex may be more likely to show progressive changes, compared with brain structures that receive indirect, inhibitory connections from the cortex. These findings are also somewhat consistent with the hypothesis that overactivity of excitatory pathways in the brain may contribute to the neural degeneration that occurs in at least a subgroup of individuals with schizophrenia.

Section snippets

Participants

The subjects in the present study were selected from groups of schizophrenia (n = 139, male/female = 90/49, age = 35.0 ± 13.0 years) and healthy comparison subjects (n = 136, male/female = 73/63, age = 33.3 ± 14.1 years) that were enrolled into an ongoing study of brain structure and schizophrenia. From these subjects, 56 schizophrenia and 62 healthy comparison subjects returned for follow-up and were included in the present study. All individuals gave written informed consent for participation

Participants

Compared with the subjects who returned for follow-up, subjects who did not return were younger (30.8 ± 13.5 years, p = .027) and had a shorter duration of illness (10.5 ± 9.9 years, p = .013) at baseline, but they did not differ in psychopathology as assessed using the total scores from SAPS (p = .23) and SANS (p = .65).

For the schizophrenia subjects, a repeated-measures general linear model with time as a repeated factor on clinical symptom domain scores showed no time effect for positive

Discussion

In this study, we found that progressive change in the deep brain nuclei and hippocampal-amygdala formation in subjects with schizophrenia was of modest magnitude and extent: As predicted, the structure of the thalamus, caudate, hippocampus, and nucleus accumbens showed disease-specific progressive (shape) changes, whereas the globus pallidus did not. However, putamen and amygdala showed progressive changes that were similar in the groups of schizophrenia and comparison subjects. When adjusted

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