The aetiology of depression

Apart from the factors and mechanisms outlined on the slide, the onset and continuity of MDD are also influenced by:¹

• Epigenetic mechanisms, which might mediate gene-environment interactions
• Alterations in brain structures and function, particularly in the pre-frontal cortex, in the anterior cingulate, and in the hippocampus. Structural and functional brain differences in MDD include disrupted neuroplasticity and neurogenesis
• Dysregulated bodily stress systems, such as a chronically overactive autonomic nervous system, or an abnormally functioning hypothalamo-pituitary-adrenal axis
• The gut-brain axis, with gut bacteria signalling to the central nervous system through the vagal nerve either directly or through secondary metabolites such as short-chain fatty acids.

Reference:

1. Marx W, Penninx BWJH, Solmi M, et al. Major depressive disorder. Nat Rev Dis Primers 2023; 9 (1): 44.