Summary of our contributions:
- Identified seasonal variation in brain μ-opioid receptor (MOR) signalling (J Neurosci, 2021), awarded Publication of the Year.
- Discovered MOR signalling in brown adipose tissue and its seasonal modulation (EJNMMI, 2023).
- Revealed brain–BAT interaction mechanisms via MOR signalling (EJNMMI, 2025).
- Proposed a novel MOR-mediated mechanism for seasonal affective disorder (book chapter, 2025).
- Demonstrated seasonal dopamine D2/3 receptor changes (EJNMMI, 2024).
- Revealed reduced glucose metabolism in social brain regions during dark seasons (J. Biol. Rhythms, 2025).
Seasonal affective disorder (SAD) affects a substantial proportion of people living in Finland. Our work has contributed to understanding the underlying neurotransmission mechanisms of SAD, particularly by revealing seasonal patterns in mu-opioid receptor (MOR) signaling.
Using a large PET imaging dataset of brain MOR availability in healthy individuals, we discovered an inverted-U shaped relationship between MOR levels and local daylength variation (Sun L. et al., Journal of Neuroscience, 2021). This finding was validated in animal models, where rats were exposed to photoperiodic cycles mimicking natural daylength changes (Sun L. et al., 2021).
Subsequently, Sun and colleagues demonstrated that brown adipose tissue (BAT) expresses MOR and exhibits seasonal fluctuations in MOR signaling (Sun L. et al., EJNMMI, 2022). As BAT plays a central role in energy homeostasis, the presence of MOR signaling in BAT suggests a potential cross-talk between the central nervous system and peripheral metabolic regulation. Indeed, our further study (Sun L. et al., EJNMMI, 2025) showed that this brain-BAT interaction is modulated by season, with enhanced coupling observed during the darker months.
In summary, our research has advanced the understanding of brain–body mechanisms underlying SAD, highlighting a pivotal role for MOR signaling. Given MOR’s central role in social cognition and reward processing, its seasonal fluctuations in both the brain and peripheral energy systems may contribute to seasonal mood changes. Dysregulation of this seasonal MOR signaling dynamic may underlie the pathophysiology of SAD.
Dr. Sun has been interviewed by Yle, Turun Sanomat, and Forbes due to relevant scientific findings.
Key Publications:
- Lihua Sun (2025), The endogenous opioid neurotransmission and seasonal affective disorders, Book chapter of “Handbook of the Biology and Pathology of Mental Disorders”, Springer
- Lihua Sun, …, Anne Roivainen (2025). Dark seasons enhance brain and brown adipose tissue interactions related to mu-opioid receptor signaling. European Journal of Nuclear Medicine and Molecular Imaging.
- Lihua Sun, …, Lauri Nummenmaa (2024). Seasonal variation in D2/3 dopamine receptor availability in the human brain, European Journal of Nuclear Medicine and Molecular Imaging
- Lihua Sun, …, Anne Roivainen (2022). [11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue. European Journal of Nuclear Medicine and Molecular Imaging.
- Lihua Sun, …, Lauri Nummenmaa (2021). Journal of Neuroscience, 41(6), 1265–1273.
- Kyoungjune Pak, …, Lihua Sun (2025). Impact of Day Length on Brain Glucose Metabolism in Men: A Large-Scale Repeated Measures PET Study. Journal of Biological Rhythms.
- Lihua Sun, …, Kaisa M Hartikainen (2016). Human brain reacts to transcranial extraocular light. PLoS ONE.