Pink winter sky. Image credit: Yang (CC0)
Seasonal affective disorder (SAD), also known as winter depression, is characterized by depressive episodes that occur in winter but can remit spontaneously in spring or summer. It is one of the most common forms of seasonal mood disorder, affecting around 1–10% of the general population.
SAD is thought to be triggered by reduced daylight exposure during shorter winter days. Although circadian disruption has been implicated in its pathophysiology, the underlying mechanisms remain poorly understood.
A distinguishing feature of SAD is excessive sleep (hypersomnolence) during winter, the cause of which remains unknown. This symptom suggests that sleep regulation may vary with seasonal changes in day length, and that the mechanisms controlling sleep under short winter days may differ from those operating during other seasons.
To elucidate the mechanisms underlying winter hypersomnolence in SAD, Chen et al. first sought to understand how sleep is regulated under different day lengths, particularly under short, winter-like days. Characterizing these mechanisms may provide insights into the causes of winter hypersomnolence in SAD, potentially shedding light on its pathophysiology.
Chen et al. studied circadian clock genes, a network of genes coding for proteins that act as an internal clock by changing their activity levels in a rhythmic pattern. They tested fruit fly mutants of different circadian clock genes under a range of day lengths.
They found that CRYPTOCHROME (CRY), a light receptor known primarily for resetting the circadian clock, helps fruit flies stay awake under short, winter-like days. Loss of CRY resulted in excessive sleep under short days, resembling the winter hypersomnolence observed in patients with SAD.
Genetic and pharmacological analyses revealed that CRY acts in neurons that synthesize the inhibitory neurotransmitter GABA. Under typical circumstances, GABA enhances sleep by inhibiting neurons that promote arousal. Increased levels of CRY, however, activate these neurons and so promote wakefulness. CRY is degraded by light and can thus accumulate to higher levels under short days, potentially contributing to sleep and wakefulness.
The study by Chen et al. revealed a mechanism that selectively regulates sleep under short, winter-like days in fruit flies. Given the conservation of molecular mechanisms underlying sleep regulation between invertebrates and mammals, similar components may contribute to the regulation of human sleep, and their disruption could play a role in winter hypersomnolence. If this mechanism is conserved in mammals, light-dependent regulation of sleep could potentially be harnessed to modulate sleep and wakefulness in both patients and healthy individuals.
