Depression poses a significant global public health challenge in modern society. According to data from the World Health Organization, approximately 322 million people worldwide suffer from depression. Preliminary research by our project team has found that early stress increases the risk of individual depression, but the biological mechanisms involved remain unclear. Additionally, it has been observed that the concentration of short-chain fatty acids (SCFAs), metabolites of the gut microbiota, is decreased in individuals with depression and is associated with changes in brain function. Furthermore, abnormal connectivity between the cerebellum and brain in depressed individuals has been linked to early stress and SCFAs levels, mediating the relationship between SCFAs and the severity of depression. Therefore, the aim of this project is to investigate the role of the microbiota-gut-brain axis and cerebellum-brain functional connectivity in the mechanisms of early stress and depression, which is crucial for understanding the occurrence of depression.
To achieve our research objectives, acquiring a large amount of data is essential. We need access to the UK Biobank platform to obtain psychological assessment data, physical examination data, and various laboratory testing data. We will study the impact of individual early experiences, family environment, and other factors on the occurrence of depression, combining physiological data to explore the role of gut microbiota and their metabolites in depression. We will investigate at which stage of depression brain changes occur. Approaching from a multi-omics perspective, we aim to comprehensively explore the pathogenesis of depression.
Using data from the UK Biobank, our study aims to investigate the differences in gut microbiota structure, SCFAs concentration, inflammatory factors, protein types and concentrations, and cerebellum-brain functional connectivity between two groups: individuals with depression and healthy controls. We will analyze the effects of different patterns of early stress exposure on depression in adolescents and explore the connection between gut microbiota dysbiosis, abnormal SCFAs metabolism, and the occurrence of depression in response to early stress. Additionally, we plan to utilize brain imaging data to obtain SC-FC coupling values and employ Mendelian randomization methods to examine the causal relationship between these changes and the onset of depression.
