BackgroundNon-suicidal self-injury (NSSI) commonly occurs among adolescents with major depressive disorder (MDD), causing adverse effects on the physical and mental health of the patients. However, the underlying neurobiological mechanism of NSSI in adolescents with MDD (nsMDDs) remains unclear, and there are still challenges in the treatment. Studies have suggested that sertraline administration could be an effective way for treatment.MethodsTo verify the effectiveness and to explore the neurobiological processes, we treated a group of adolescents with nsMDDs with sertraline in this study. The brain spontaneous activity alteration was then investigated in fifteen unmedicated first-episode adolescent nsMDDs versus twenty-two healthy controls through the resting-state functional magnetic resonance imaging. Besides the baseline scanning for all participants, the nsMDDs group was scanned again after eight weeks of sertraline therapy to examine the changes after treatment.ResultsAt pre-treatment, whole brain analysis of mean amplitude of low-frequency fluctuation (mALFF) was performed to examine the neuronal spontaneous activity alteration, and increased mALFF was found in the superior occipital extending to lingual gyrus in adolescent nsMDDs compared with controls. Meanwhile, decreased mALFF was found in the medial superior frontal in adolescent nsMDDs compared with controls. Compared with the pre-treatment, the nsMDDs group was found to have a trend of, respectively, decreased and increased functional neuronal activity at the two brain areas after treatment through the region of interest analysis. Further, whole brain comparison of mALFF at pre-treatment and post-treatment showed significantly decreased spontaneous activity in the orbital middle frontal and lingual gyrus in adolescent nsMDDs after treatment. Also, depression severity was significantly decreased after treatment.ConclusionThe abnormal functional neuronal activity found at frontal and occipital cortex implied cognitive and affective disturbances in adolescent nsMDDs. The trend of upregulation of frontal neuronal activity and downregulation of occipital neuronal activity after sertraline treatment indicated that the therapy could be effective in regulating the abnormality. Notably, the significantly decreased neuronal activity in the decision related orbital middle frontal and anxiety-depression related lingual gyrus could be suggestive of reduced NSSI in adolescent MDD after therapy.