Multiday rhythms shape mood dynamics in depression

Mood fluctuations in major depressive disorder are difficult to anticipate. The biological neural rhythms that organize mood dynamics over days to weeks remain unknown. In individuals implanted with a chronic neural sensing and stimulation device for treatment-resistant depression, we collected years-long intracranial neural recordings alongside daily mood ratings. Both mood and limbic neural activity fluctuated cyclically with multiday (multidien) periodicities of 2–34 days. An individual’s daily phase position within mood cycles tracked depression severity, distinguishing whether symptoms were rising, peaking, or resolving. Neural rhythms led mood cycles and forecast an individual’s mood trajectory up to 30 days in advance, outperforming models based on raw neural activity. Electrical stimulation reshaped these rhythms, shifting individuals away from the peak-depression phase of their multidien cycle. Our results identify multidien rhythms as an organizing principle of mood in depression and a forecastable, modifiable target for chronotherapeutic neuromodulation.