Major depressive disorder (MDD) is marked by significant changes to the local synchrony of spontaneous neural activity across various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of local correlations. A newly developed method sensitive to classical anatomo-functional boundaries, Iso-Distant Average Correlation (IDAC), was therefore used to examine depression associated alterations to the local functional connectivity of the brain.

One-hundred and forty-seven adolescents and young adults with MDD and 94 healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. Whole-brain functional connectivity maps of intracortical neural activity within iso-distant local areas (5–10, 15–20, and 25–30 mm) were generated to characterize local fMRI signal similarities.

Across all spatial distances, MDD participants demonstrated greater local functional connectivity of the bilateral posterior hippocampus, retrosplenial cortex, dorsal insula, fusiform gyrus, and supplementary motor area. Local connectivity alterations in short and medium distances (5–10 and 15–20 mm) in the mid insula cortex were additionally associated with expressive suppression use, independent of depressive symptom severity.

Our study identified increased synchrony of the neural activity in several regions commonly implicated in the neurobiology of depression. These effects were relatively consistent across the three distances examined. Longitudinal investigation of this altered local connectivity will clarify whether these differences are also found in other age groups and if this relationship is modified by increased disease chronicity.