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BackgroundLongitudinal metabolic changes of total choline (tCho), creatine + phosphocreatine (total creatine, tCr), and N-acetylaspartate (NAA) in the pregenual anterior cingulate cortex (pACC) of patients with major depressive disorder (MDD) have not been well evaluated.PurposeTo evaluate the longitudinal changes of the metabolic levels of tCho, tCr, and NAA in the pACC of MDD patients and normal controls with the use of Single-voxel 1HMRS.Material and MethodsSingle-voxel 1HMRS was acquired in the pACC of 21 female patients with MDD and 26 age- and gender–matched controls. Follow-up scans were acquired in 10 patients with MDD and 15 controls after 9–10 months from baseline scans. Absolute concentrations of tCho, tCr, and NAA, and the ratios of NAA/tCr and tCho/tCr were calculated and compared between and within groups.ResultsThe patient group showed slightly improved clinical symptoms, as measured by Beck’s Depression Inventory (P = 0.035), after treatment with antidepressants. Comparison of baseline scans between the groups showed no differences in any of the absolute metabolite concentrations or ratios. The NAA/tCr ratio in the pACC of patients with MDD showed a significant decrease in the follow-up scan (P = 0.032), and the NAA/tCr ratio of the baseline scan showed logarithmic negative association with illness duration (P = 0.024).ConclusionA progressive decrease in the NAA/tCr ratio in the pACC of patients with MDD was demonstrated and the decrease in this ratio was at the highest rate in the early period after illness onset. These findings indicate the neuronal degeneration and dysfunction of the pACC, and the importance of early clinical intervention in female patients with MDD.