Though irregular sleep patterns and mood disorders have long been known to accompany one another, the biological link between the two had, until now, remained a mystery. However, a new study published in the Proceedings of the National Academy of Sciences suggests that a single protein may act as a key driver of both conditions, and that a genetic mutation disrupting the production of this molecule could therefore provide the missing connection.
The protein in question is called period circadian protein homolog 3 and has previously been associated with the regulation of the circadian clock. This is the bodys internal time-keeping system, often referred to as the body clock, which controls a number of physiological processes over the course of each day including sleep patterns.
In a previous study, the researchers had noted that three members of the same family who suffered from a disorder calledfamilial advanced sleep phase (FASP) all carried faulty versions of the gene PER3, which is responsible for the synthesis of period circadian protein homolog 3. FASP is a condition causing people to become extreme morning types,meaning they wake exceptionally early each morning sometimes as early as 2 a.m. but also become very sleepy in the early evening.
All three of these individuals also suffered from seasonal affective disorder, which is characterized by a tendency to become depressed during the winter, leading the researchers to wonder whether PER3 could regulate both sleep patterns and mood.
To test this, they engineered mice to carry genetic mutations disrupting the production of this key protein, ensuring that its synthesis was totally blocked in some of the mice and partially blocked in others. They then observed the sleep patterns of these rodents when subjected to various seasonal simulations. For instance, to mimic the effects of summer, the researchers placed the mice in 12 hours of light followed by 12 hours of darkness, while those kept in winter-like conditions were afforded just fourhours of light a day.
Seasonal affective disorder is characterized by an increase in depression-like symptoms during the short winter days. icsnaps/Shutterstock
Compared to regular mice, these subjects displayed a disrupted sleeping pattern, which was found to be more pronounced in those that entirely lacked PER3 than those with partial synthesis. This was particularly extreme in the winter light regimethat, when combined with a total deficit of the protein, produced a four-hour shift in sleep patterns.
These results indicate that PER3 is at least partlyresponsible for regulating the sleep timings of these mice, although researchers wanted to know if it also generates an increase in seasonal affective disorder. To determine this, they subjected the mice to a number of behavioral tests, such as dangling them by their tails and observing how long it took them to give up struggling something the researchers say is a decent indicator of depression-like symptoms.
They noted that the engineered mice all gave up much quicker than non-altered mice, and that those lacking PER3 were faster to abandon hope than those with only a partial mutation. These mice also displayed a reduced appetite for sugary water, indicating that they were not gaining as much pleasure as the control mice from this treat. The fact that both of these symptoms were alleviated by administering a common anti-depressant called imipramine would seem to suggest that the mice were indeed suffering from a depression-like state with the same pharmacological properties as human depression.
Furthermore, the study authors note that these behavioral effects were greatly increased under winter-like conditions, indicating that, as well as generating FASP, PER3 likely regulates mood disorders such as seasonal affective disorder.