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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., (Copyright © 2020. Published by Elsevier B.V.)

Bipolar disorder (BD) has been associated with impaired executive functioning and integrity of fronto-limbic white matter tracts. The evaluation of these factors in young offspring of patients with BD (BDoff) as a high-risk group offers an opportunity to investigate factors that could predict vulnerability to the disorder. This study aims to examine the correlation between neurocognition and neuroimaging findings to evaluate the potential for these findings as biomarkers for the early recognition of BD. We enrolled BDoff (n = 16) who were aged between 12 and 18. Participants were assessed using clinical and neurocognitive tests. In addition, structural brain magnetic resonance and diffusion tensor imaging data were obtained. Mean fractional anisotropy (FA) and mean diffusivity (MD) values of the superior longitudinal fasciculus (SLF) and cingulum were extracted and correlations with neuropsychological data were analyzed. FA values in the SLF were negatively correlated with Stroop interference, the Wisconsin Card Sorting Test, and the Trail Making Test (B-A) scores. MD values in the cingulum were inversely correlated with the Child and Youth Resilience Measure and positively correlated with higher scores on the Barratt Impulsiveness Scale-Attentional. These findings provide a link between features of the brain and cognitive dysfunction in BDoff., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bipolar disorder (BD) is associated with cognitive dysfunction which has also been reported in offspring of individuals with BD (BDoff). However, it remains unclear whether cognitive underperformance in BDoff is associated with the presence of history of subclinical syndromes associated with risk for BD. To address this knowledge gap we assessed executive function, visual and verbal memory, working memory, processing speed and verbal fluency in 21 offspring with clinical high risk (CHR; BDoff+CHR), 54 offspring without CHR (BDoff-non-CHR), and 50 healthy individuals without familial risk of BD. BDoff underperformed compared to controls in most cognitive tasks. There was no significant neurocognitive difference between BDoff+CHR and BDoff-non-CHR except in the fluency/central executive domain (Cohen's d = 0.60, p = 0.03). Our results suggest that cognitive dysfunction in multiple domains is associated with familial predisposition to BD regardless of CHR status. On the other hand, abnormalities in central executive processes might be more pronounced in BDoff+CHR than BDoff-non-CHR. Further longitudinal studies investigating cognitive trajectory of BDoff and its interaction with the emergence of subclinical syndromes are needed to fully characterize the relationship between cognition and mood dysregulation in BD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is associated with significant cognitive heterogeneity. In recent years, a number of studies have investigated cognitive subgroups in BD using data-driven methods and found that BD includes several subgroups including a severely impaired and a neurocognitively intact cluster. Studies in offspring of BD (BDoff) are particularly important to establish the timing of emergence of cognitive subgroups but studies investigating cognitive heterogeneity in BDoff are lacking. Our aim was to investigate cognitive heterogeneity in BDoff and the relationship between cognitive heterogeneity and putative clinical stages of BD., Methods: Seventy-one euthymic BDoff and 50 healthy controls were assessed using clinical measures and a battery of neuropsychological tests. Neurocognitive subgroups were investigated using latent class analysis., Results: Three neurocognitive subgroups, including a severe impairment group, a good performance cluster, and a subgroup characterized by intermediate/selective impairment was found. Both severe and intermediate level impairment subgroups underperformed healthy controls in processing speed, verbal fluency, visual memory and working memory. Deficits in verbal memory and executive functions were only evident in severe impairment subgroup. The putative stage of the illness had no significant effect on cognitive clustering of BDoff. Trait impulsivity scores were significantly increased in severe and intermediate impairment clusters but not in the cognitively good functioning subgroup of BDoff., Limitations: The cross-sectional nature of the study was the main consideration., Conclusion: These results suggest that cognitive heterogeneity is premorbid characteristic of BD and cognitive subgroups of BDoff emerge prior to the onset of illness and prodromal symptoms., (Copyright © 2019 Elsevier B.V. All rights reserved.)