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Structural and functional deficits associated with schizophrenia are observed prior to the onset of psychosis and differ according to the stage of illness. However, most previous studies concentrated on a limited period during the illness, and it remains uncertain how these abnormalities develop throughout the entire disease course. In the current study, we investigated the gray matter (GM) and regional neural activity alterations in subjects at 4 different stages of schizophrenia. The subjects comprised 53 genetic high risk (HR) individuals, 26 ultra-high risk (UHR) individuals, 58 patients with first-episode schizophrenia (FES), 41 patients with chronic schizophrenia (ChSz) and 39 healthy controls (HC), all of whom underwent structural and resting-state functional MRI scanning. Gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) values were compared voxelwise among the five groups using voxel-based morphometry (VBM) and the software REST. Correlations among structural, functional abnormalities and PANSS scores in the FES group were evaluated by partial correlation analysis and multiple stepwise regression. Pronounced GMV decline was observed in the bilateral occipital lobe, left orbital frontal cortex, bilateral superior parietal lobule (SPL), right middle temporal gyrus (MTG), gyrus rectus and medial superior frontal gyrus (SFG) in the FES group and in the bilateral occipital lobe in the HR group. The FES patients also showed increased ALFF in the caudate and decreased ReHo in the bilateral inferior parietal lobule (IPL) and precuneus. The ChSz patients displayed increased ALFF in the right hippocampus. The GMV of the right MTG and SPL and the ReHo of the precuneus were negatively correlated with the general psychopathology scale, while the GMV of the right MTG was negatively correlated with the total score on the Positive and Negative Syndrome Scale (PANSS). The GMV of the right occipital cortex and SPL were associated with the ALFF of the caudate, the GMV of the right SPL was associated with the ReHo of the bilateral IPL and precuneus. GM deficits and regional dysfunction are evident prior to the onset of psychotic symptoms and are more prominent during the onset of illness than during any other phase. The right MTG and SPL, the striatum and the DMN may play important roles in the pathological changes underlying schizophrenia. [ABSTRACT FROM AUTHOR]