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

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. 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. 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. Relatively shorter follow-up duration, medications confounding, and modest sample size. 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. • We found distinctive alterations in global brain connectivity among depressed adolescents with subthreshold mania. The alterations include a decrease in the right Medial Superior Frontal Gyrus (SFGmed.R)/Superior Frontal Gyrus (SFG) and an increase in the right Precuneus and left Postcentral Gyrus. • Significantly, the GBC index in the SFGmed.R/SFG displayed an opposite pattern between the two patient groups compared to HCs, decreasing in Sub MD patients while increasing in nSub MD patients, demonstrating good discriminative efficacy and suggesting specific early alterations in bipolar disorder (BD). • Additionally, an increased GBC index in the right Inferior Temporal Gyrus (ITG.R) emerged as a common alteration across both patient groups, presenting a gradient in the extent of alterations with Sub MD ＞nSub MD ＞HCs. [ABSTRACT FROM AUTHOR]