Scott Alexander examines the synapse hypothesis of depression, which links decreased synaptogenesis to various depression research findings, and raises questions for future investigation. Longer summary

This post explores the synapse hypothesis of depression, which proposes that decreased synaptogenesis, regulated by the protein complex mTORC1, may be the underlying cause of depression. Scott Alexander reviews various lines of research on depression, including life adversity, inflammation, serotonin, glutamate, folate, and electroconvulsive therapy, and shows how the synapse hypothesis could potentially unify these diverse findings. He then expresses some skepticism about the theory, noting that it's easy to find connections between any proposed cause and various symptoms. The post concludes with six questions or areas of confusion that the author hopes will be addressed in future research, including why decreased synaptogenesis should cause depression specifically, why BDNF can't be used as a direct treatment, and how bipolar disorder fits into this framework. Shorter summary