René Kahn1,2, Guusje Collin1, Lianne Scholtens1, Manon Hillegers1,3, Martijn van den Heuvel1; 1UMC Utrecht, 2Icahn School of Medicine, 3Erasmus MC
Background: Emerging evidence suggests disruptions in the wiring organization of the brain’s network in schizophrenia and bipolar disorder. As the importance of genetic predisposition has been firmly established in these illnesses, children (offspring) of patients constitute an at-risk population. This study examines connectome organization in children at familial high risk for psychosis. Methods: Diffusion-weighted MRI scans were collected from 127 non-psychotic offspring, aged 8 to 18 years (13.5 years on average), of a parent diagnosed with schizophrenia (SZ-offspring; N = 28) or bipolar disorder (BD-offspring; N = 60), and community controls (N = 39). Resting-state fMRI scans were available for 82 subjects. Anatomical and functional brain networks were reconstructed and examined using graph theoretical analysis. Results: SZ-offspring were found to show connectivity deficits of the brain’s central rich club system relative to both controls and BD-offspring. The disruption in anatomical rich club connectivity in SZ-offspring was associated with increased modularity of the functional connectome. In addition, increased coupling between structural and functional connectivity (SC-FC coupling) of long-distance connections was observed in both SZ- and BD-offspring. Conclusions: This study shows lower levels of anatomical rich club connectivity in non-psychotic young offspring of schizophrenia patients. This finding suggests that the brain’s anatomical rich club system is affected in at-risk youths, reflecting a connectome signature of familial risk for psychotic illness. Moreover, finding no rich club deficits in offspring of bipolar disorder patients suggest a differential effect of genetic predisposition for schizophrenia versus bipolar disorder on the developmental formation of the connectome
