Major depressive disorder (MDD) is a leading cause of disability worldwide. Investigating early-stage alterations in cerebral intrinsic activity among drug-naive patients may enhance our understanding of MDD’s neurobiological mechanisms and contribute to early diagnosis and intervention.

To examine alterations in the amplitude of low-frequency fluctuation (ALFF) in first-episode, drug-naive MDD individuals and explore associations between ALFF changes and clinical parameters, including depression severity and illness duration.

A total of 30 first-episode, drug-naive MDD individuals (mean illness duration 14 weeks) and 52 healthy controls were included in this study. Resting-state functional magnetic resonance imaging was used to obtain whole-brain ALFF measurements. Voxel-based ALFF maps were compared between MDD and healthy control groups using a two-sample t-test. Simple regression analysis was performed to assess associations between ALFF and clinical measures, including Hamilton Rating Scale for Depression (HAMD) scores and illness duration.

MDD individuals exhibited significantly increased ALFF in the dorsal anterior cingulate cortex and vermal subregion V3 of the cerebellum. Additionally, ALFF in the right dorsolateral prefrontal cortex was negatively correlated with HAMD scores (r = –0.591, P < 0.001). However, no significant association was found between ALFF and illness duration.

This study demonstrates early-stage ALFF alterations in drug-naive MDD patients, particularly in brain regions implicated in cognitive and emotional regulation. These findings suggest potential neuroimaging biomarkers for the early diagnosis and intervention of MDD.