In this study, we utilized advanced quantitative MRI techniques, specifically Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Мacromolecular Proton Fraction Mapping, to investigate microstructural differences and alterations in the specific regions in patients diagnosed with major depressive disorder. Previous studies have illustrated that the cingulate and prefrontal gyrus, along with the amygdala, are involved in emotional processing and the development of abnormal emotional responses in depression. Our findings revealed no significant interaction between Мacromolecular proton fraction Mapping with depressive disorder. However, patients with major depressive disorder exhibited a statistically significant increase in mean, axial and radial diffusivity (F = 6.3, p = 0.01, F = 5.0, p = 0.03, F = 7.08, p = 0.01, respectively) in the bilateral amygdala compared to healthy controls, as well as in mean and radial diffusivity in the anterior cingulate cortex (F = 5.61, p = 0.02, F = 7.08, p = 0.01, respectively). These results suggest that altered molecular diffusion characteristics in the amygdala and the anterior cingulate cortex may be specifically associated with major depressive disorder. The identification of novel markers for brain microstructural changes could have implications for early prediction of depressive disorder. Our study demonstrates the utility of new quantitative MRI techniques in assessing structural alterations on the molecular level in the brain and enhances our understanding of the pathophysiology of depression.