Anterior cingulate cortex-related functional dysconnectivity in adolescents with major depressive disorder with and...

Given the involvement of the anterior cingulate cortex (ACC) in the pathomechanisms of loneliness among adolescents with major depressive disorder (MDD), research is required to determine the associations between loneliness and specific ACC subregions, namely the subgenual ACC (sgACC), perigenual ACC (pgACC), and dorsal ACC (dACC).

This study included 15 adolescents with MDD and severe loneliness, 24 adolescents with MDD but without severe loneliness, and 32 healthy controls, with all evaluated using the UCLA Loneliness Scale and the 17-item Hamilton Depression Rating Scale (HDRS). Severe loneliness was identified by a total UCLA Loneliness Scale score of greater than 60. Seed-based functional connectivity (FC) analysis was conducted using the bilateral sgACC, pgACC, and dACC as seeds.

Significant differences were observed in the left dACC-seeded FCs between the three groups. Specifically, the two depression groups exhibited less negative FC between the left dACC and right precuneus compared with the control group. More positive FCs were observed between the left dACC and left posterior cingulate cortex (PCC) as well as the left ventroanterior ACC in adolescents with MDD and severe loneliness than in those with MDD only. The dACC-seeded FC with the left PCC and right precuneus positively correlated with the total HDRS and UCLA Loneliness Scale scores.

Aberrant FCs between the left dACC and left PCC as well as the left ventroanterior ACC were specific to loneliness among adolescents with MDD, with functional dysconnectivity between the left dACC and right precuneus being common to depression.