Accelerated biological brain aging in major depressive disorder

Major depressive disorder (MDD) patients commonly encounter multiple types of functional disabilities, such as social, physical, and role functioning. MDD is related to an accreted risk of brain atrophy, aging-associated brain diseases, and mortality. Based on recently available studies, there are correlations between notable biological brain aging and MDD in adulthood. Despite several clinical and epidemiological studies that associate MDD with aging phenotypes, the underlying mechanisms in the brain remain unknown. The key areas in the study of biological brain aging in MDD are structural brain aging, impairment in functional connectivity, and the impact on cognitive function and age-related disorders. Various measurements have been used to determine the severity of brain aging, such as the brain age gap estimate (BrainAGE) or brain-predicted age difference (BrainPAD). This review summarized the current results of brain imaging data on the similarities between the manifestation of brain structural changes and the age-associated processes in MDD. This review also provided recent evidence of BrainPAD or BrainAGE scores in MDD, brain structural abnormalities, and functional connectivity, which are commonly observed between MDD and age-associated processes. It serves as a basis of current reference for future research on the potential areas of investigation for diagnostic, preventive, and potentially therapeutic purposes for brain aging in MDD.