Identifying biomarkers for serious mental illnesses (SMI) has significant implications for prevention and early intervention. In the current study, changes in whole brain structural and functional connectomes were investigated in youth at transdiagnostic risk over a one-year period. Based on clinical assessments, participants were assigned to one of 5 groups: healthy controls (HC
n = 33), familial risk for serious mental illness (stage 0
n = 31), mild symptoms (stage 1a
n = 37), attenuated syndromes (stage 1b
n = 61), or discrete disorder (transition
n = 9). Constrained spherical deconvolution was used to generate whole brain tractography maps, which were then used to calculate connectivity matrices for graph theory analysis. Graph theory was also used to analyze correlations of functional magnetic resonance imaging (fMRI) signal between pairs of brain regions. Linear mixed models revealed structural and functional abnormalities in global metrics of small world lambda, and resting state networks involving the fronto-parietal, default mode, and deep grey matter networks, along with the visual and dorsal attention networks. Machine learning analysis additionally identified changes in nodal metrics of betweenness centrality in the angular gyrus and bilateral temporal gyri as potential features which can discriminate between the groups. Our findings further support the view that abnormalities in large scale networks (particularly those involving fronto-parietal, temporal, default mode, and deep grey matter networks) may underlie transdiagnostic risk for SMIs.