Objective: Many studies have reported that patients with schizophrenia often have structural abnormalities of the anterior cingulate cortex (ACC) and that some of these seem to be of genetic origin, therefore predating the onset of illness. The present study aimed to investigate whether these alterations in the ACC are genetic in origin by comparing the morphological patterns of three groups: normal controls, subjects at genetic high risk (GHR) for psychosis, and patients with schizophrenia. The relationships between morphological variations and executive function were also investigated.

Methods: This study examined the magnetic resonance images of cingulate sulcus/paracingulate sulcus (CS/PCS) folding patterns in 222 subjects (103 normal subjects, 30 individuals at GHR, and 89 patients with schizophrenia) and evaluated differences in the morphological and asymmetrical patterns of the ACC among groups. Neurocognitive tests were then performed and differences in cognitive performance were analyzed according to morphological variation.

Results: Differences in PCS folding were detected; the control group was significantly more likely than were other groups to show a well-developed left PCS (p=0.009) and leftward asymmetry of the PCS (p<0.001). However, neither GHR subjects (p=0.346) nor patients (p=0.784) showed this leftward asymmetry. No statistically significant differences in CS continuity were observed. A more prominent left PCS (p=0.031) and leftward PCS asymmetry (p=0.030) were both associated with higher scores on the working memory task.

Conclusion: The results suggest that GHR subjects have distinct neurodevelopmental anomalies that resemble those of patients with schizophrenia even though they do not display any psychotic symptoms. Certain developmental alterations in the ACC, such as the loss of leftward sulcal asymmetry in patients with schizophrenia, might be related to genetic factors. Additionally, this morphological alteration might partly account for the impaired executive function in schizophrenia.