Convergent evidence from multimodal imaging reveals amygdala abnormalities in schizophrenic patients and their first-degree relatives

Abstract

Background: Shared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.

Methods: Using a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.

Results: Schizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.

Conclusions: Our findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.

Figure 1. Surface renderings representing the results from the analysis of structural MRI data.

Statistical parametric maps of VBM analysis are superimposed on the population, landmarked-and surface-based (PALS) atlas of human cerebral cortex using CARET software (http://brainvis.wustl.edu). (A) Regions with significantly (p<0.05, corrected) decreased gray matter density in schizophrenic patients and their parents compared with their respective counterparts are shown in cool color. Color bar indicates the z-value. (B) An overlapping surface rendering of the between-group statistical parametric maps (SZ versus HC1, light green; PA versus HC2, light blue). Yellow areas represent areas of overlap between the two statistical parametric maps. SZ, schizophrenic patients; HC1, healthy controls for schizophrenic patients; PA, parents of schizophrenic patients; HC2, healthy controls for parents.

Figure 2. Surface renderings representing the results from the analysis of functional MRI data.

Statistical parametric maps of functional connectivity analysis of the left amygdala are superimposed on the population, landmarked-and surface-based (PALS) atlas of the human cerebral cortex using CARET software (http://brainvis.wustl.edu). (A) Within-group functional connectivity patterns. Cool color and warm color, respectively, are used to indicate regions with significantly negative connectivity and significantly positive connectivity (p<0.05, corrected) with the left amygdala. (B) Between-group functional connectivity patterns. Regions with significantly (p<0.05, corrected) altered functional connectivity (compared with their representative counterparts) with the left amygdala in schizophrenic patients and their parents are shown. Color bar indicates the z-value. (C) An overlapping surface rendering of the between-group statistical parametric maps (SZ versus HC1, light green; PA versus HC2, light blue). Yellow areas represent areas of overlap between the two statistical parametric maps. SZ, schizophrenic patients; HC1, healthy controls for schizophrenic patients; PA, parents of schizophrenic patients; HC2, healthy controls for parents.