Cortical Complexity in People at Ultra-High-Risk for Psychosis Moderated by Childhood Trauma

Abstract

Subjects with ultra-high risk (UHR) states for psychosis show brain structural volume changes similar to first-episode psychosis and also elevated incidence of environmental risk factors like childhood trauma. It is unclear, however, whether early neurodevelopmental trajectories are altered in UHR. We screened a total of 12,779 first-year Chinese students to enroll 36 UHR subjects (based on clinical interviews) and 59 non-UHR healthy controls for a case-control study of markers of early neurodevelopment. Subjects underwent 3T MRI scanning and clinical characterization, including the childhood trauma questionnaire (CTQ). We then used the CAT12 toolbox to analyse structural brain scans for cortical surface complexity, a spherical harmonics-based marker of early neurodevelopmental changes. While we did not find statistically significant differences between the groups, a trend level finding for reduced cortical complexity (CC) in UHR vs. non-UHR subjects emerged in the left superior temporal cortex (and adjacent insular and transverse temporal cortices), and this trend level association was significantly moderated by childhood trauma (CTQ score). Our findings indicate that UHR subjects tend to show abnormal cortical surface morphometry, in line with recent research; more importantly, however, this association seems to be considerably modulated by early environmental impacts. Hence, our results provide an indication of environmental or gene × environment interactions on early neurodevelopment leading up to elevated psychosis risk.

Keywords: cortical complexity; magnetic resonance imaging (MRI); psychosis; schizophrenia; spherical harmonics; ultra-high risk (UHR).

Figure 1

Group comparison indicating lower cortical complexity in ultra-high risk for psychosis (UHR) vs. non-UHR healthy controls (HC). The clusters are thresholded at p < 0.001 (uncorrected). Display of trend level findings: While there were no statistically significant (p < 0.05, FWE cluster level corrected) group differences, we observed a trend level finding for reduced cortical complexity in a cluster in the left superior temporal gyrus, extending toward the insular and transverse temporal cortices. The above image is displayed at a p < 0.001 uncorrected threshold for display purposes.

Figure 2

Conceptual (A) and statistical (B) model showing the relationship between cortical complexity and UHR/HC status being moderated by level of childhood maltreatment. Regression coefficients in (B) are calculated in a model including age and sex as covariates.

Figure 3

Graph showing the moderation effect of level of childhood maltreatment (CTQ) on the association of cortical complexity in the superior temporal gyrus (STG) and the probability of UHR status in a binominal logistic regression model. Color of the dots indicates CTQ scores, lines represent fitted regression models dependent on CTQ sum score, exemplary for CTQ score of 20 (black), 40 (dark blue), and 60 (light blue) with respective standard error intervals. The steepest curve (i.e., strongest association) between STG CC and UHR status is present at low CTQ scores and decreasing with increasing CTQ scores (as shown in the flattening curve).