1H-magnetic resonance spectroscopy imaging and diffusion tensor imaging were performed in 19 patients with mild depression and in 13 controls. The mean age of the patients was 31 years. The mean Hamilton depression score of the patients was 22.5 ± 13.2. N-acetylaspartate, choline and creatine concentrations and the average diffusion coefficient and fractional anisotropy values were measured in the bilateral hippocampus, striatum, thalamus and prefrontal deep white matter. Compared with the control group, the mild depressed patients had: (1) a higher choline/creatine ratio and a negative correlation between the choline/creatine ratio and the average diffusion coefficient in the hippocampus; (2) a lower choline/creatine ratio and a higher fractional anisotropy in the striatum; (3) a lower fractional anisotropy and a positive correlation between the fractional anisotropy and the choline/creatine ratio in the prefrontal deep white matter; and (4) a higher average diffusion coefficient and a positive correlation between the choline/creatine ratio and the N-acetylaspartate/creatine ratio in the thalamus, as well as positive correlation between the choline/creatine ratio and Hamilton depression scores. These data suggest evidence of abnormal connectivity in neurofibrotic microstructures and abnormal metabolic alterations in the limbic-cortical-striatal-pallidal-thalamic neural circuit in patients with mild depression.