Altered amygdala shape trajectories and emotion recognition in youth at familial high risk of schizophrenia who develop psychosis

Relatives of individuals with schizophrenia have a higher risk of developing the illness compared to the general population. Thus, youth at familial high risk (FHR) offer a unique opportunity to identify neuroimaging-based endophenotypes of psychosis. Previous studies have identified lower amygdalo-hippocampal volume in FHR, as well as lower verbal memory and emotion recognition. However, whether these phenotypes increase the risk of transition to psychosis remains unclear. To determine if individuals who develop psychosis have abnormal neurodevelopmental trajectories of the amygdala and hippocampus, we investigated longitudinal changes of these structures in a unique cohort of 82 youth FHR and 56 healthy controls during a 3-year period. Ten individuals from the FHR group converted to psychosis. Longitudinal changes were compared using linear mixed-effects models. Group differences in verbal memory and emotion recognition performance at baseline were also analyzed. Surface-based morphometry measures revealed variation in amygdalar shape (concave shape of the right dorsomedial region) in those who converted to psychosis. Significantly lower emotion recognition performance at baseline was observed in converters. Percent trial-to-trial transfer on the verbal learning task was also significantly impaired in FHR, independently of the conversion status. Our results identify abnormal shape development trajectories in the dorsomedial amygdala and lower emotion recognition abilities as phenotypes of transition to psychosis. Our findings illustrate potential markers for early identification of psychosis, aiding prevention efforts in youth at risk of schizophrenia.