Gene Mutation Linked To Seasonal Affective Disorder

Scientists believe that seasonal affective disorder is caused by a reduction in the exposure to daylight which usually occurs during the winter months. What is uncertain, is what makes some individuals more susceptible to changes in mood, compared to others.

Now, researchers from the University of California – San Francisco (UCSF) School of Medicine have identified a mutation in a human gene which may put a person at risk of developing seasonal affective disorder. The results of the study were published in the journal, Proceedings of the National Academy of Sciences.

Seasonal affective disorder – sometimes called seasonal depression – affects approximately 3 percent of Americans. The average age of onset for the condition is between the ages of 18 and 30.

Depression, mood changes, anxiety and sleep problems are all symptoms of seasonal affective disorder, which generally occurs in the winter when the days are shorter and there is less natural light. Due to the high prevalence of the disorder during the winter, researchers believe that changes in light are to blame.

The theory is that the changes in natural light disrupt an individual’s circadian rhythm, leading to the characteristic symptoms of seasonal affective disorder. Some researchers have also suggested that the disorder may be triggered by elevated levels of melatonin, a hormone that balances our sleep-wake cycles.

It’s been shown that more melatonin is produced in the dark, so the elevated hormone levels could be responsible for seasonal affective disorder in the winter. As it’s unclear why some people develop seasonal affective disorder, and others don’t, the researchers decided to investigate whether there was a genetic basis to the condition.

Previous research by Dr. Ying-Hui-Fu, professor of neurology at UCSF, and his colleagues, found that a number of genetic mutations were associated with a disorder called familial advanced sleep phase (FASP) syndrome. FASP is characterized by an accelerated body clock that causes a person to fall asleep earlier (around 8 or 9pm), and wake earlier (around 4 to 5 am).

The researchers performed a genetic analysis of individuals with a family history of FASP and/or seasonal affective disorder, and found that three people who had a family history of both shared a common mutation in the PER3 gene. The discovery led the researchers to believe that this gene could play a role in mood and sleep patterns.

To further study the effects of the gene, the researchers introduced a mutated copy of PER3 into genetically engineered mice, and studied their reaction to variable periods of light and dark. While the mice acted normally when the length of the day and night were equal, once the dark period was extended to 20 hours, the mice showed symptoms similar to depression.

When the functionality of the PER3 gene was completely knocked-out, the depression-like symptoms became worse. According to the researchers, the symptoms of human depression are nearly impossible to measure in mice, however there are certain measures of behavior in mice – including quick surrender in challenging situations – that could indicate how PER3 regulates human mood.

“It’s an exciting time,” said Fu. “People have known for decades that light and mood were linked, but this is our first real finger-hold on the problem.” While they are unsure about the mechanism behind PER3’s possible regulation of mood, the researchers say they have plans to further study the genetic link.