Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.