Disrupted brain structural connectivity in Pediatric Bipolar Disorder with psychosis

Bipolar disorder (BD) has been linked to disrupted structural and functional connectivity between prefrontal networks and limbic brain regions. Studies of patients with pediatric bipolar disorder (PBD) can help elucidate the developmental origins of altered structural connectivity underlying BD and provide novel insights into the aetiology of BD. Here we compare the network properties of whole-brain structural connectomes of euthymic PBD patients with psychosis, a variant of PBD, and matched healthy controls. Our results show widespread changes in the structural connectivity of PBD patients with psychosis in both cortical and subcortical networks, notably affecting the orbitofrontal cortex, frontal gyrus, amygdala, hippocampus and basal ganglia. Graph theoretical analysis revealed that PBD connectomes have fewer hubs, weaker rich club organization, different modular fingerprint and inter-modular communication, compared to healthy participants. The relationship between network features and neurocognitive and psychotic scores was also assessed, revealing trends of association between patients' IQ and affective psychotic symptoms with the local efficiency of the orbitofrontal cortex. Our findings reveal that PBD with psychosis is associated with significant widespread changes in structural network topology, thus strengthening the hypothesis of a reduced capacity for integrative processing of information across brain regions. Localised network changes involve core regions for emotional processing and regulation, as well as memory and executive function, some of which show trends of association with neurocognitive faculties and symptoms. Together, our findings provide the first comprehensive characterisation of the alterations in local and global structural brain connectivity and network topology, which may contribute to the deficits in cognition and emotion processing and regulation found in PBD.Te authors gratefully thank Mikkel Petersen for his help in the DTI analysis and Angus Stevner for his inputs on group consistency testing. M.L.K. was supported by the ERC Consolidator Grant: CAREGIVING (No. 615539), TrygFonden Charitable Foundation and by Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117). J.C. was supported by the Portuguese Foundation for Science and Technology CEECIND/03325/2017, Portugal). G.D. was supported by the Spanish Research Project SAF2010-16085 and the FP7-ICT BrainScales. Te clinical and neuroimaging data used in this study was supported by the Medical Research Council (M.R.C. G0500092) and the Oxford Hospital Services Research Committee (OHSCR)