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Background: Major depressive disorder (MDD) is one of the most prevalent mental disorders during adolescence, and early diagnosis and treatment are important. We aimed to characterize the microstructure of the brain in medication-naïve adolescents with first-episode MDD.Methods: Patients with MDD (N = 31) and healthy controls (N = 27) participated in this study and severity of depressive symptoms, duration of untreated depressive episode, demographic data, and diffuse tensor imaging data were collected. A comparative analysis of patients and healthy controls was performed, and the effect of medication on the brain`s integrity was investigated through comparison before and after 3 months of treatment in the patient group. Tract-based spatial statistics was used for diffusion tensor image analysis.Results: In the patient group, functional anisotropy (FA) values were significantly higher at the genu of the corpus callosum, body of the corpus callosum, and right anterior corona radiata than in healthy controls. After 3 months of treatment, FA values were significantly decreased in the left anterior limb of the internal capsule, left posterior limb of the internal capsule, and left superior longitudinal fasciculus.Limitations: The sample size is relatively small and 3-month treatment period was relatively short.Conclusion: FA values of patients with MDD were increased compared to healthy controls and decreased after treatment. These results suggested that pharmacological treatments in the early stages of MDD might restore the brain`s integrity. [ABSTRACT FROM AUTHOR]