Abnormal hippocampal–thalamic white matter tract development and positive symptom course in individuals at ultra-high risk for psychosis

BACKGROUND/OBJECTIVES: Abnormal development of the hippocampus has been reported in adolescents at ultra-high risk (UHR) for psychosis and thalamic abnormalities have been found. However, the white matter connections between the hippocampus and the thalamus have not been studied. The connections between these regions are of key importance to our understanding of the pathophysiology of psychosis. METHODS: Twenty-six UHR and 21 healthy age-matched controls were tested at a baseline assessment and 12 months later. Symptoms were assessed at both the time points and all the participants underwent diffusion tensor imaging scans. We used tractography to trace the white matter connections in each individual between the thalamus and hippocampus and then extracted fractional anisotropy (FA) to assess white matter structural integrity. RESULTS: There was a significant group by time interaction indicating that FA decreased in UHR, and increased in controls over 12 months. Across both groups, baseline FA of the thalamic–hippocampal tract was predictive of positive symptoms at 12-month follow-up. Critically, this pattern remained significant in UHR individual group alone. At baseline, those with higher FA, indicative of abnormal white matter development, show higher positive symptoms 1 year later. CONCLUSIONS: Here, we provide evidence to indicate that there are differences in white matter development in hippocampal–thalamic connections, both of which are important nodes in networks associated with schizophrenia. Furthermore, abnormal developmental patterns in UHR individuals are associated with positive symptom course.