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Background: Bipolar disorder (BD) might be associated in disturbances in brain networks. However, little is known about the abnormalities in structural brain connectivity which might be related to vulnerability to BD and predictive of the emergence of manic symptoms. No previous study has investigated the effect of subthreshold syndromes on structural dysconnectivity in offspring of parents with BD (BDoff).Methods: We investigated diffusion weighted images of 70 BDoff and 48 healthy controls (HC). Nineteen of the 70 BDoff had presented with subthreshold syndromes indicating a clinical high-risk (BDoff-CHR) and other 51 BDoff had no such history (BDoff-non-CHR). Global and regional network properties, rich club organization and inter-regional connectivity in BDoff and healthy controls were investigated using graph analytical methods and network-based-statistics (NBS).Results: Global properties of WM networks appeared to be intact in BDoff-CHR and BDoff-non-CHR. However, decreased regional connectivity in right occipito-parietal areas and cerebellum was a common feature of both BDoff groups. Importantly, decreased interregional connectivity between nodes in right and left prefrontal regions, nodes in right prefrontal lobe and right temporal lobe and nodes in left occipital area and left cerebellum were evident in BDoff-CHR but not BDoff-non-CHR.Limitations: The cross-sectional nature of the study was the main consideration.Conclusion: Decreased regional connectivity in right posterior brain regions might be related to vulnerability to BD. On the other hand, interregional dysconnectivity in anterior frontal and limbic regions and left posterior brain regions might be evident in individuals genetically at risk for developing BD who had experienced subthreshold mood symptoms. [ABSTRACT FROM AUTHOR]