Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression

Abstract

Objective: 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.

Method: 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.

Results: 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.

Conclusions: 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.

Fig. 1.

Control Comparison Analyses. Gray matter volumes lower in high-risk group (red), first episodic group (blue), and chronic group (green) compared with healthy controls. Significance thresholded with a false discovery rate at P < .01. z represents the z coordinates in Talairach space. L, left; R, right; A, anterior; P, posterior.

Fig. 2.

Subtraction Analysis in First-Episode Schizophrenia (FES) Vs High-Risk Group. Red: lower gray matter volume in FES group. Blue: lower gray matter volume in high-risk group. Significance thresholded with a false discovery rate at P < .01. z represents the z coordinate in the Talairach space. L., left; R., right.

Fig. 3.

Subtraction Analysis Chronic Vs First-Episode Schizophrenia (FES) Group. Red: lower gray matter volume in chronic schizophrenia. Blue: lower gray matter volume in FES. Significance thresholded with a false discovery rate at P < .01. z represents the z coordinate in the Talairach space. L, left; R, right.