Connectome-wide network analysis of youth with Psychosis-Spectrum symptoms

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Adults with psychotic disorders have dysconnectivity in critical brain networks, including the default mode (DM) and the cingulo-opercular (CO) networks. However, it is unknown whether such deficits are present in youth with less severe symptoms. We conducted a multivariate connectome-wide association study examining dysconnectivity with resting state functional magnetic resonance imaging in a population-based cohort of 188 youths aged 8–22 years with psychosis-spectrum (PS) symptoms and 204 typically developing (TD) comparators. We found evidence for multi-focal dysconnectivity in PS youths, implicating the bilateral anterior cingulate, frontal pole, medial temporal lobe, opercular cortex and right orbitofrontal cortex. Follow-up seed-based and network-level analyses demonstrated that these results were driven by hyper-connectivity among DM regions and diminished connectivity among CO regions, as well as diminished coupling between frontal and DM regions. Collectively, these results provide novel evidence for functional dysconnectivity in PS youths, which show marked correspondence to abnormalities reported in adults with established psychotic disorders.

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Thanks to the acquisition and recruitment team: Karthik Prabhakaran, Ryan Hopson, Jeff Valdez, Raphael Gerraty, Marisa Riley, Jack Keefe, Elliott Yodh and Rosetta Chiavacci. Thanks to Mark Elliott for image acquisition support. Thanks to Frank Mentch for data management. This work was supported by RC2 grants from the National Institute of Mental Health MH089983 and MH089924 and P50MH096891. Support for developing statistical analyses (SNV, RTS, TDS) was provided by a seed grant by the Center for Biomedical Computing and Image Analysis (CBICA) at Pennsylvania. Support for network analytics was provided by the Institute for Translational Medicine and Therapeutics (ITMAT) at Pennsylvania to DSB and TDS. Additional support was provided by K23MH098130 to TDS, R01MH101111 to DHW, K01MH102609 to DRR, K08MH079364 to MEC, R01NS085211 to RTS, T32MH065218-11 to SNV and the Dowshen Program for Neuroscience.

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Correspondence to T D Satterthwaite.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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