Abstract
Major depressive disorder (MDD) is associated with altered spontaneous brain activity, commonly assessed by regional homogeneity (ReHo), a measure of local synchronization of neuronal synchronization. While previous research has highlighted ReHo changes in MDD, their age-related variations remain underexplored. To address this, this study investigated first-episode MDD patients from the REST-meta-MDD project, dividing them into three age subgroups: young (16-24 years), adults (25-39 years), and middle-aged participants (40-54 years), and examined the age-related ReHo changes and interactions with disease. The results revealed distinctive age-specific patterns of ReHo alternations. Specifically, young patients showed decreased ReHo in the right middle frontal gyrus, right superior parietal lobule, and left inferior temporal gyrus; adult patients exhibited reductions in the right superior frontal gyrus, left middle frontal gyrus, and right inferior frontal gyrus; and middle-aged patients displayed reductions in the right paracentral lobule, right inferior temporal gyrus, and left middle occipital gyrus. A progressive age-related ReHo decline was observed in the left postcentral gyrus, left superior parietal lobule, and left superior temporal gyrus. Significant disease effects was noted in the right superior frontal gyrus, with an age-by-disease interaction in the right superior occipital gyrus. Receiver operating characteristic (ROC) analysis indicated robust diagnostic potential for MDD-related ReHo patterns in adult and middle-aged groups. These findings suggest ReHo as a promising biomarker for first-episode MDD, with dynamic, age-dependent characteristics across the lifespan.