All multicellular life that we know of has circadian rhythms- oscillations in biological activity that repeat every 24 hours. Correspondingly, Earth’s tilt has prompted in many species the evolution of annual rhythms which follow the seasons. Some animals migrate, others hibernate or have mating seasons, and plants cycle their leaves through the year. But despite our heritage from a long lineage of mammals who exhibit such seasonal patterns, they are noticeably absent in humans. Though it is true that the primates we descended from evolved in regions near the equator, where the climate is relatively steady year round, hundreds of millions of years of prior evolution is a lot to erase. Do humans have seasonal rhythms?

Examining traits that vary with the seasons is, as one might expect, very difficult. In the age of electric light and indoor heating, the cues that seasonal changes in day length and temperature provide are often masked. Even so, hidden in the noisy data, scientists have indeed found evidence that there are some vestiges of inherent seasonality in humans.

The most well-known seasonal trait in humans is Seasonal Affective Disorder (SAD). Like other psychiatric disorders, it’s manifestation is likely on a spectrum- numerous individuals are affected to some degree by seasonal changes but only a few reach a severity which can be diagnosed as a clinical disorder. Many have probably noticed changes in their moods with the seasons, and offhandedly chalked it up to SAD. But there are hints that other health issues follow a similar pattern; for example epilepsy to cardiovascular disease, whose onset and severity both appear to uptick slightly in the winter. Unlike SAD, we can’t easily connect these diseases to changing day length. But the data consistently indicates a trend of a few percent and all points in a similar direction, indicating these patterns may be the tip of an iceberg and reflective of more fundamental changes in our bodies.

Further clues may lie with one of the few other well-established seasonal components to human biology: the immune system. The immune system tends to be more active in winter months, leading to more sensitive and pronounced inflammatory responses. As a result, autoimmune disorders such as arthritis tend to flare up during these times. There also appears to be a bidirectional relationship between certain inflammatory markers and mood, potentially creating a link with SAD and other psychiatric disorders. But we run into a chicken-and-the-egg problem here, which is whether inherent fluctuations in immune system activity are causing the increased incidence of disease flare-ups, or whether external influences generate more disease and hence a more active immune system. In biology, the most accurate answer to questions of causality like this is usually a mix of both, which invites the question: do humans have an inherent seasonal rhythmicity, or are they just responding to an environment with one? If you remove an animal from environmental cues such as light, it will continue to exhibit a circadian rhythm of behavior. This means that circadian rhythms are endogenous: originating from the organism itself. Theoretically, seasonal rhythmicity could also be endogenous. To explore this- since we can’t isolate a human for an entire year- we need to look at an even more basic biological processes- gene expression.

As various proteins are needed by our bodies, the genes coding for them are ‘turned on’ or ‘off’ as necessary within each cells’ nucleus. Researchers can take a snapshot of which suite of genes are ‘on’- being expressed- to get a picture of the body’s responses to certain conditions, like exercise, or the introduction of a pathogen. It is through these pictures that we’ve discovered just how many human genes are expressed in a spontaneous and regular 24 hour pattern. But researchers have recently found out that many of these genes may also oscillate on an annual basis.

One integral study, using samples from around the world, found that immune-modulating genes cycled throughout the year in a manner consistent with the observations of disease seasonality; greater risk of inflammatory disease in the winter, lower in the summer. But strikingly, this pattern was not observed in people from The Gambia. Instead, the peak of their inflammatory immune profile occurred in the summer. The authors suggest that this may be due to the Gambian rainy season in the summer months, when tropical diseases such as malaria- a powerful selective influence- are more prevalent.

This tells us that the seasonal rhythms found in humans are not necessarily due to shifts in day length or temperature, as Gambia is near to the Equator. Human seasonal patterning appears to be a flexible module that tunes itself to the environment it resides in, relying on whatever cues are prevalent around it. However, even this information doesn’t inform us whether these rhythms are coded into our genome, as they may merely be driven by our body’s response to environmental pathogen load.

To address these sorts of difficult questions, biologists often use the disruption of a process as a window into its normal function. Sometimes, we can disrupt something experimentally, in a controlled way, and learn specific things about the system from the outcome. In humans, where we are unable to use such controls, we have to turn to disorders- natural perturbations of the homeostatic human system. Dementia is one example of such a disrupted system. Among other things, dementia patients exhibit a profound disruption of the circadian system as their disease progresses- this is part of the reason they have such erratic sleep schedules.

Using brain samples from deceased Alzheimer’s patients, researchers measured gene expression data from throughout the year and different times of day. They found that Alzheimer’s patients exhibited a misalignment of their circadian rhythms, as had been reported previously. But they also found that their seasonal rhythms behaved similarly- there was a slight misalignment of the seasonal gene expression rhythms in demented patients compared to healthy people. If seasonality in humans were entirely due to pathogens in the environment, then we would not expect such a shift in the rhythms of these Alzheimer’s patients, as they were in contact with the same general environment as the healthy controls. Though it is possible that the disrupted brains of Alzheimer’s patients merely misregister these environmental cues, the strikingly similar behaviors of the seasonal and circadian rhythms, and its consistency in one direction, imply the former may be endogenous to some degree.

Of course, even if humans do exhibit an endogenous seasonal rhythm, it is heavily influenced by the world around it. Biology is not a closed system, and nearly everything that goes on in the body is due to the interaction between genetic coding and environmental signals. Perhaps the seasonal clock is established through cues read by the immune system early in development. Or the system is tunable, and changes throughout life with an individual’s current environment (an interesting byproduct of this model would be a seasonal ‘jetlag’ if the body can’t change rhythms within one year-cycle). Regardless of the exact mechanism, it does appear the human body has some sort of inherent yearly timekeeper, silently ticking away to keep us in step with nature’s rhythms. If you removed a human from environmental cues, perhaps they would still be able to tell you when winter was coming.

PhD Candidate in Biomedical Sciences at UCSF