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

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.

Predicting Cognition and Psychosis in Young Adults With 22q11.2 Deletion Syndrome.

OBJECTIVE: To assess the extent to which the trajectories of intellectual, academic achievement, executive functioning, attention, working memory, and emotion recognition tests will be predictive of psychosis in young adults with 22q11.2 deletion syndrome (22q11DS). METHODS: Eighty-two participants with 22q11DS were assessed for psychiatric disorders and neuropsychological functioning with validated instruments. Siblings and community controls were employed as comparison groups. RESULTS: Individuals with 22q11DS differed significantly from siblings and controls in longitudinal trajectories of visual and auditory working memory as well as academic achievement. Longitudinal trajectories of cognitive set shifting, reading decoding, and emotion recognition predicted the presence of positive symptoms of psychosis in early adulthood. Cognitive set shifting improved at a slower rate for individuals with 22q11DS + psychosis than those without psychosis. Emotion recognition increased steadily in individuals without psychosis, whereas for those with psychosis, scores increased until approximately 15 years of age, at which point they began to decrease rapidly. A similar, but more subtle effect, was seen for reading decoding. CONCLUSIONS: Our data are the first to go beyond IQ assessments in assessing longitudinal neuropsychological outcomes and risk for psychosis in 22q11DS. Individuals with 22q11DS who developed psychotic symptoms improved less appreciably and continued to demonstrate difficulties with cognitive flexibility relative to individuals with 22q11DS who did not have psychotic symptoms. Individuals with 22q11DS who developed psychosis had weaker reading skills in childhood and, after an initial improvement into adolescence, these individuals with psychosis had a decline in reading skills. In 22q11DS, cognitive deficits are both (a) traits that are preexisting and raise the risk for psychosis and (b) associated with the onset of psychotic symptoms. Future research should consider the extent to which cognitive set shifting and reading decoding are related to the Verbal IQ declines observed in the 22q11DS population.