Altered resting-state functional connectivity in young children at familial high risk for psychotic illness: A preliminary study.

Multiple lines of evidence suggest that illness development in schizophrenia and other psychotic disorders predates the first psychotic episode by many years. In this study, we examined a sample of 15 pre-adolescent children, ages 7 through 12 years, who are at familial high-risk (FHR) because they have a parent or sibling with a history of schizophrenia or related psychotic disorder. Using multi-voxel pattern analysis (MVPA), a data-driven fMRI analysis, we assessed whole-brain differences in functional connectivity in the FHR sample as compared to an age- and sex-matched control (CON) group of 15 children without a family history of psychosis. MVPA analysis yielded a single cluster in right posterior superior temporal gyrus (pSTG/BA 22) showing significant group-differences in functional connectivity. Post-hoc characterization of this cluster through seed-to-voxel analysis revealed mostly reduced functional connectivity of the pSTG seed to a set of language and default mode network (DMN) associated brain regions including Heschl's gyrus, inferior temporal gyrus extending into fusiform gyrus, (para)hippocampus, thalamus, and a cerebellar cluster encompassing mainly Crus I/II. A height-threshold of whole-brain p < .001 (two-sided), and FDR-corrected cluster-threshold of p < .05 (non-parametric statistics) was used for post-hoc characterization. These findings suggest that abnormalities in functional communication in a network encompassing right STG and associated brain regions are present before adolescence in at-risk children and may be a risk marker for psychosis. Subsequent changes in this functional network across development may contribute to either disease manifestation or resilience in children with a familial vulnerability for psychosis.