A meta-analysis of structural and functional brain abnormalities in early-onset schizophrenia

Early-onset schizophrenia (EOS) patients demonstrate brain changes that are similar to severe cases of adult-onset schizophrenia. Neuroimaging research in EOS is limited due to the rarity of the disorder. The present meta-analysis aims to consolidate MRI and functional MRI findings in EOS. Seven voxel-based morphometry (VBM) and 8 functional MRI studies met the inclusion criteria, reporting whole-brain analyses of EOS vs healthy controls. Activation likelihood estimation (ALE) was conducted to identify aberrant anatomical or functional clusters across the included studies. Separate ALE analyses were performed, first for all task-dependent studies (Cognition ALE) and then only for working memory ones (WM ALE). The VBM ALE revealed no significant clusters for gray matter volume reductions in EOS. Significant hypoactivations peaking in the right anterior cingulate cortex (rACC) and the right temporoparietal junction (rTPJ) were detected in the Cognition ALE. In the WM ALE, consistent hypoactivations were found in the left precuneus (lPreC), the right inferior parietal lobule (rIPL) and the rTPJ. These hypoactivated areas show strong associations with language, memory, attention, spatial, and social cognition. The functional co-activated networks of each suprathreshold ALE cluster, identified using the BrainMap database, revealed a core co-activation network with similar topography to the salience network. Our results add support to posterior parietal, ACC and rTPJ dysfunction in EOS, areas implicated in the cognitive impairments characterizing EOS. The salience network lies at the core of these cognitive processes, co-activating with the hypoactivating regions, and thus highlighting the importance of salience dysfunction in EOS.