This Gene May Be Why You're Tired and Sad

Humans are delicate enough so that changing our clocks by one hour throws some of us for a loop. As the clock sprang forward Sunday, so too did the annual reminders that the time change is directly correlated with an increase in traffic collisions and heart attacks. But if you find yourself struggling today, there may be a scientific reason: Some people are born with a gene mutation that makes them more susceptible to poor sleep and seasonal depression. Just because it’s nearly spring doesn’t mean it’s sunny.

A recent study from the University of California San Francisco is the first to identify a genetic connection to seasonal affective disorder (SAD) and sleep patterns. In the journal PNAS, professors Ying-Hui Fu and Louis Ptáček explain that after decades of studying the genetic basis of sleep, they have identified the gene that causes people to experience both SAD and Familial Advance Sleep Phase (FASP) — the condition of having a “fast” biological clock, causing one to go to bed and wake up super early. The mutation is in the gene PER3 — a circadian gene that sits “at the nexus of sleep and mood.”

“It’s an exciting time,” said Fu in a release. “People have known for decades that light and mood were linked, but this is our first real finger-hold on the problem.”

By interviewing and examining hundreds of people with unusual sleep issues, Fu and Ptáček identified three members of a family, all of whom have a mutation in the gene PER3. To better understand this gene and the affects on circadian rhythms and seasonal depression, the scientists introduced it into genetically engineered mice.

Here’s a quick refresher: Circadian rhythms are the physical, mental, and behavioral changes primarily caused by the cycles of light and darkness we experienced during the day. These change the levels of interacting molecules in cells that make up the “biological clock,” which, in turn, control the body’s circadian rhythms.

In the study, the researchers altered the mice’s exposure to darkness, thus manipulating their concepts of day and season. When they received a normal “dose”, 12 hours of light and 12 hours of darkness, the mice slept well and acted normally. But when they only got four hours of light and 20 hours of darkness, the waking and sleeping cycles of the genetically modified mice were four hours off from the cycles of the control group — just like the humans with PER3.

The researchers acknowledge that they weren’t able put a mouse on a little couch and gauge its feelings, but they were still able to deem their mice “depressed,” according to established tests for rodent depression. A clear sign of mouse depression is when an individual animal, put into difficult circumstances, gives up easily.

The researchers also found that when they inserted PER3 into isolated cells in a petri dish, the mutated gene caused significantly less protein compared to a normal gene. This led the researchers to hypothesize that PER3 most likely causes the destabilization of the related PER2 protein, which plays a large role in regulating an organism’s biological clock. The loss of this protein is what leads someone to experience FASP.

In their next study, the researchers plan to conduct tests and determine exactly why the PER3 mutation affects mood. They plan to incorporate mice models once again, and examine the brain circuits related to mood and depression.

Still, although your genes may be causing your sleep-deprived lifestyle, they are never solely the cause of restless nights.

“We as humans are not always good at listening to our biology,” Ptáček told the San Jose Mercury News. “We set alarms, we drink coffee, and we drink alcohol.”