Serotonin and depression

Serotonin is a neurotransmitter produced mainly in the gut (90%) and in the brainstem. In the central nervous system, it is involved in regulating mood, sleep, appetite, memory, and impulsivity. For decades, the "serotonin hypothesis" of depression proposed that depression was caused by a serotonin deficit — a model that helped justify the development of SSRIs.

However, the reality is more complex. A widely discussed 2022 scientific review questioned the evidence for the simplified serotonin hypothesis. Depression is likely the result of multiple systems: serotonin, norepinephrine, dopamine, glutamate, inflammation, the hypothalamic-pituitary-adrenal axis (cortisol), and neuroplastic factors (BDNF).

Antidepressants that act on serotonin (SSRIs, SNRIs) remain effective for many people — not necessarily because they "correct" a serotonin deficit, but possibly because of effects on multiple systems over the course of ongoing use. The neurobiology of depression remains an active area of research.