Longitudinal trajectories of cortical thickness as a biomarker for psychosis in individuals with 22q11.2 deletion syndrome

Abstract

Objective: 22q11.2 deletion syndrome (DS) or velo-cardio-facial syndrome (VCFS) is a genetic condition that has been identified as the highest genetic risk factor for developing psychotic illnesses. This unique biological nature of 22q11DS provides a valuable opportunity to explore predictive biomarkers of psychosis. In this study, we examined the relationship of cortical thickness and surface area between various brain regions and prodromal symptoms of psychosis.

Methods: 75 probands with 22q11DS, 32 age-matched controls and 28 siblings underwent MRIs over 2 or 3 timepoints. Longitudinal mixed model regression analyses, with age as an interaction variable, were carried out to study the differences in longitudinal trajectories of change in average cortical thickness and surface area over 6-9years. Similar analyses were carried out to examine the relationship with positive prodromal symptoms of psychosis.

Results: Significant differences were noted in the inferior and superior parietal regions in both the average thickness and longitudinal change in cortical thickness with age between the probands and controls. Significant associations were also noted between regions in the frontal cortex and positive prodromal symptoms among probands. No associations were noted with cortical surface area.

Conclusion: Our results indicate that individuals with 22q11DS who develop positive prodromal symptoms demonstrate differential longitudinal trajectories of cortical thickness in some regions of the frontal lobe. Our results suggest that the pruning stage associated with adolescent brain development may be disrupted.

Keywords: 22q11DS; Cortical morphology; Psychosis; Schizophrenia; Velo-cardio-facial syndrome.