Distinct global brain connectivity alterations in depressed adolescents with subthreshold mania and the relationship with processing speed: Evidence from sBEAD Cohort

Background: Bipolar disorder (BD) is a progressive condition. Investigating the neuroimaging mechanisms in depressed adolescents with subthreshold mania (Sub_MD) facilitates the early identification of BD. However, the global brain connectivity (GBC) patterns in Sub_MD patients, as well as the relationship with processing speed before the onset of full-blown BD, remain unclear.

Methods: The study involved 72 Sub_MD, 77 depressed adolescents without subthreshold mania (nSub_MD), and 69 gender- and age-matched healthy adolescents (HCs). All patients underwent a clinical follow-up ranging from six to twelve months. We calculated the voxel-based graph theory analysis of the GBC map and conducted the TMT-A test to measure the processing speed.

Results: Compared to HCs and nSub_MD, Sub_MD patients displayed distinctive GBC index patterns: GBC index decreased in the right Medial Superior Frontal Gyrus (SFGmed.R)/Superior Frontal Gyrus (SFG) while increased in the right Precuneus and left Postcentral Gyrus. Both patient groups showed increased GBC index in the right Inferior Temporal Gyrus. An increased GBC value in the right Supplementary Motor Area was exclusively observed in the nSub_MD-group_. There were opposite changes in the GBC index in SFGmed.R/SFG between two patient groups, with an AUC of 0.727. Additionally, GBC values in SFGmed.R/SFG exhibited a positive correlation with TMT-A scores in Sub_MD-group.

Limitations: Relatively shorter follow-up duration, medications confounding, and modest sample size.

Conclusion: These findings suggest that adolescents with subthreshold BD have specific impairments patterns at the whole brain connectivity level associated with processing speed impairments, providing insights into early identification and intervention strategies for BD.