Apathy mediates the relationship between uncinate fasciculus fractional anisotropy and depression in healthy adults.

Many patients with neurodegenerative and psychiatric diseases, such as Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD), suffer from apathy, which manifests as a lack of emotion, interest, and motivation. Therefore, research on the relationship between apathy and brain structure in patients with the disease is accumulating. However, the relationship between the tendency for apathy and brain structure in healthy people has hardly been clarified. Since changes in the brain's microstructure can occur even in individuals before they develop a specific disease, it is meaningful from the perspective of preventive medicine to clarify the latent apathy and changes in brain structure in healthy people. In addition, it is unclear and worth clarifying how apathy relates to the relationship between depression, which shares some symptoms with apathy, and the brain. Therefore, in this study, using diffusion tensor imaging data collected from 173 participants (69 men and 104 women) aged 23-69 years, along with responses to two psychological questionnaires (the Apathy Scale and the Center for Epidemiologic Studies Depression Scale), we analyzed the relationship between apathy and fractional anisotropy (FA) of four fibers, the uncinate fasciculus (UF), corpus callosum (CC), superior longitudinal fasciculus (SLF), and cingulum. As a result, there was a significant negative correlation between UF FA and apathy (p = 0.003), like previous studies in patients with AD and bvFTD. This relationship remained almost unchanged in partial correlation analysis controlling for sex, age, whole brain gray matter volume (GMV), depression, etc. (p = 0.001). Furthermore, the results of path analysis showed that apathy fully mediated the relationship between UF FA and depression (p = 0.001). This is the first study to show that apathy tendency in people who perceive themselves as healthy is associated with UF FA and mediates the relationship between UF FA and depression.