Aberrant Regional Homogeneity in First-Episode, Drug-Naïve Adolescents with Major Depressive Disorder

Background: Adolescent major depressive disorder (MDD) is common, but the neural mechanisms that underlie it remain poorly understood. Imaging work has been carried out mainly in adults, and data from adolescents with a first, untreated episode are still scarce. In this cross-sectional resting-state functional MRI study, we assessed spontaneous local activity using regional homogeneity (ReHo) together with caudate-seeded functional connectivity (FC), and related both measures to the clinical profile of first-episode, drug-naïve adolescent MDD patients. Methods: The sample comprised 31 adolescents with MDD (aged 10–19 years) and 25 age-matched healthy controls (HC). ReHo and caudate-seeded FC were computed for each participant, and we tested whether these measures were related to symptom severity on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Results: Compared with HC, adolescents with MDD showed significantly increased ReHo in three clusters within a gray-matter mask (cluster-level p < 0.05, FWE-corrected): the right lingual gyrus, the left supramarginal gyrus, and the left insula. No region showed significantly decreased ReHo, and caudate-seeded FC showed no reliable group difference; the increases reported here are therefore presented as exploratory findings. Two regions showed a positive association with symptom severity that withstood Bonferroni correction: the left supramarginal gyrus (r = 0.51, p = 0.007) and the right lingual gyrus (r = 0.49, p = 0.009). Conclusions: In first-episode, drug-naïve adolescent MDD, exploratory analyses showed elevated ReHo in the lingual gyrus, insula, and supramarginal gyrus, pointing to altered synchrony of local BOLD signals in circuits supporting visual processing, interoception, and somatosensory integration. Caudate-seeded functional connectivity showed no robust group difference. Because the design was cross-sectional and the sample modest, these results await confirmation in larger, prospective cohorts.