ArticleNature metabolism2024
Human PERIOD3 variants lead to winter depression-like behaviours via glucocorticoid signalling.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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Who cites it
4 citing papers in PubMed.
- Octanoic acid treatment alleviates cold-induced depression-like behaviors via targeting the AKR1B1-PGF2α pathway.iScience · 2026Article
- Sunshine duration and episodes of mental disorders and the inverse effect modification by ambient temperature.BMC medicine · 2026Article
- The gut microbiota mediates depression-like behaviors in mice with chronic Echinococcus multilocularis infection.NPJ biofilms and microbiomes · 2026Article
- CRY1 Lysine 151 Regulates Circadian Rhythms Through Ubiquitination-Independent Protein Interactions.International journal of molecular sciences · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
Our brain adapts to seasonal changes. Mis-adaptations may lead to seasonal patterns in several psychiatric disorders, but we know little regarding the underlying mechanisms. Our previous work identified two variants in the human circadian clock gene PERIOD3 (PER3), that is, P415A and H417R, which are associated with winter depression, but whether and how these variants lead to the disorder remain to be characterized. Here we find that male mice carrying human P415A and H417R display winter depression-like behaviours that are caused by the actions of P415A and H417R in the adrenal gland. Systemic corticosterone level is downregulated in adaptation to shortening of day length, while P415A and H417R eliminate this downregulation by increasing corticosterone synthesis. Enhanced glucocorticoid signalling represses the transcription of Tph2, which encodes the rate-limiting enzyme of serotonin synthesis, leading to increased depression-like behaviours. Taken together, our findings unveil a mechanism according to which human variants contribute to seasonal mood traits.
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Registered trials
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