Article

Brain Anatomical Abnormalities in High-Risk Individuals, First-Episode, and Chronic Schizophrenia: An Activation Likelihood Estimation Meta-analysis of Illness Progression

Department of Psychiatry, University of Hong Kong, Hong Kong Special Administrative Region, China.
Schizophrenia Bulletin (Impact Factor: 8.61). 08/2009; 37(1):177-88. DOI: 10.1093/schbul/sbp073
Source: PubMed

ABSTRACT The present study reviewed voxel-based morphometry (VBM) studies on high-risk individuals with schizophrenia, patients experiencing their first-episode schizophrenia (FES), and those with chronic schizophrenia. We predicted that gray matter abnormalities would show progressive changes, with most extensive abnormalities in the chronic group relative to FES and least in the high-risk group.
Forty-one VBM studies were reviewed. Eight high-risk studies, 14 FES studies, and 19 chronic studies were analyzed using anatomical likelihood estimation meta-analysis.
Less gray matter in the high-risk group relative to controls was observed in anterior cingulate regions, left amygdala, and right insula. Lower gray matter volumes in FES compared with controls were also found in the anterior cingulate and right insula but not the amygdala. Lower gray matter volumes in the chronic group were most extensive, incorporating similar regions to those found in FES and high-risk groups but extending to superior temporal gyri, thalamus, posterior cingulate, and parahippocampal gryus. Subtraction analysis revealed less frontotemporal, striatal, and cerebellar gray matter in FES than the high-risk group; the high-risk group had less gray matter in left subcallosal gyrus, left amygdala, and left inferior frontal gyrus compared with FES. Subtraction analysis confirmed lower gray matter volumes through ventral-dorsal anterior cingulate, right insula, left amygdala and thalamus in chronic schizophrenia relative to FES.
Frontotemporal brain structural abnormalities are evident in nonpsychotic individuals at high risk of developing schizophrenia. The present meta-analysis indicates that these gray matter abnormalities become more extensive through first-episode and chronic illness. Thus, schizophrenia appears to be a progressive cortico-striato-thalamic loop disorder.

Download full-text

Full-text

Available from: Xin Di, Jul 01, 2015
0 Followers
 · 
165 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: While schizophrenia and bipolar disorder have been assumed to share phenotypic and genotypic features, there is also evidence for overlapping brain structural correlates, although it is unclear whether these relate to shared psychotic features. In this study, we used voxel-based morphometry (VBM8) in 34 schizophrenia patients, 17 euthymic bipolar I disorder patients (with a history of psychotic symptoms), and 34 healthy controls. Our results indicate that compared to healthy controls schizophrenia patients show grey matter deficits (p<0.05, FDR corrected) in medial and right dorsolateral prefrontal, as well as bilaterally in ventrolateral prefrontal and insular cortical areas, thalamus (bilaterally), left superior temporal cortex, and minor medial parietal and parietooccipital areas. Comparing schizophrenia vs. bipolar I patients (p<0.05, FDR corrected) yielded a similar pattern, however, there was an additional significant reduction in schizophrenia patients in the (posterior) hippocampus bilaterally, left dorsolateral prefrontal cortex, and left cerebellum. Compared to healthy controls, the deficits in bipolar I patients only reached significance at p<0.001 (uncorr.) for a minor parietal cluster, but not for prefrontal areas. Our results suggest that the more extensive prefrontal, thalamic, and hippocampal deficits that might set apart schizophrenia and bipolar disorder might not be related to mere appearance of psychotic symptoms at some stage of the disorders. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 04/2015; 165(2-3). DOI:10.1016/j.schres.2015.04.007 · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early intervention research in schizophrenia has suggested that brain structural alterations might be present in subjects at high risk of developing psychosis. The heterogeneity of regional effects of these changes, which is established in schizophrenia, however, has not been explored in prodromal or high-risk populations. We used high-resolution MRI and voxel-based morphometry (VBM8) to analyze grey matter differences in 43 ultra high-risk subjects for psychosis (meeting ARMS criteria, identified through CAARMS interviews), 24 antipsychotic-naïve first-episode schizophrenia patients and 49 healthy controls (groups matched for age and gender). Compared to healthy controls, resp., first-episode schizophrenia patients had reduced regional grey matter in left prefrontal, insula, right parietal and left temporal cortices, while the high-risk group showed reductions in right middle temporal and left anterior frontal cortices. When dividing the ultra-high-risk group in those with a genetic risk vs. those with attenuated psychotic symptoms, the former showed left anterior frontal, right caudate, as well as a smaller right hippocampus, and amygdala reduction, while the latter subgroup showed right middle temporal cortical reductions (each compared to healthy controls). Our findings in a clinical psychosis high-risk cohort demonstrate variability of brain structural changes according to subgroup and background of elevated risk, suggesting frontal and possibly also hippocampal/amygdala changes in individuals with genetic susceptibility. Heterogeneity of structural brain changes (as seen in schizophrenia) appears evident even at high-risk stage, prior to potential onset of psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.
    Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.10.041 · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Studies have shown that patients with schizophrenia and their siblings share decreased graymatter (GM) volumes in certain brain regions, which may represent candidate endophenotypes of schizophrenia. However, the specificity and utility of these possible endophenotypes in relation to schizophrenia remain unclear. Methods: Twenty drug-naive, first-episode schizophrenia patients and 20 first-degree unaffected siblings from the same families as the patients (USS group), a separate group of 25 first-degree unaffected siblings of schizophrenia patients from other families (USO group), and 43 healthy controls were recruited. Voxel-based morphometry (VBM) was used to analyze structural imaging data. Results: The VBM analysis showed a significant difference in GM volume between the combined sibling group and the control group in the left middle temporal gyrus (MTG). Group comparison showed that the patients, the USS, and the USO had significantly decreased GM volume of the left MTG compared with the controls; such a difference did not exist among the patients and the two sibling groups. A receiver operating characteristic curve (ROC curve) analysis showed good predictive value of the mean cluster volume in the left MTG to distinguish patients, USS, and USO from healthy controls. There were no significant correlations between the mean cluster volume in the left MTG and clinical variables in the patients. Conclusions: The GM volume decrease of the left MTG may be utilized as a candidate biomarker for schizophrenia. The novel design of including a USO group in our study enhances both the specificity and the heritability of the biomarker identified.
    Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.051 · 4.43 Impact Factor