In a new mouse study, a team of researchers from Vanderbilt University have come closer to figuring out the underlying brain mechanisms responsible for seasonal affective disorder (SAD). They have identified the dorsal raphe nucleus, a small region in the middle of the brain in both humans and mice, as the main hub for the disorder.
About four to six percent of Americans suffer from SAD, a type of depression linked to receiving less sunlight during the winter months.
Biologists have known that the circadian clock may play a role in the disorder and have proposed that the neurotransmitters serotonin and melatonin may be involved. Until now, however, they have been unable to identify the underlying neurobiological mechanisms responsible for the disorder.
In the new study, the researchers have localized the seasonal light cycle effects that drive SAD to a small region in the mid-brain called the dorsal raphe nucleus.
In both mice and humans, the dorsal raphe nucleus houses many specialized neurons that control serotonin levels throughout the brain. Because high concentrations of serotonin are tied to feelings of well-being and happiness while low levels are linked to depression, serotonin plays a major role in regulating an individual’s mood.
They also discovered that the day/night cycle in which individuals are born can have a long-lasting effect on the activity level of the neurons in this region.
“We got the idea for the study from a report by Viennese psychiatrists which found a season of birth correlation in SAD patients,” said the study’s lead author, graduate student Noah Green.
The researchers decided to focus on the dorsal raphe nucleus because previous studies had shown that it is linked to the brain’s master biological clock and it also responds to melatonin, a hormone that helps regulate a number of related physiological functions, such as sleep, blood pressure, and seasonal reproduction.
For the study, the researchers divided mice into three groups.
One group was born and raised in an environment with a summer-like light cycle of 16 hours of light and eight hours of dark. The second group was born and raised with a cycle of 12 hours of light and 12 hours of dark, like spring and fall. The third group was born and raised in a winter-like light cycle with eight hours of light and 16 hours of dark.
Other than the light cycle, the environments were identical.
After several tests, the findings showed that the summer-light-cycle mice exhibited lower levels of depression-like behavior than their spring/fall- or winter-light-cycle counterparts.
When the biologists looked at the brains of mice from the three groups, their findings were consistent with the behavioral testing. They found that serotonergic neurons fire faster in the summer-light-cycle mice and they had elevated levels of serotonin and the neurotransmitter norepinephrine, which is known to excite serotonergic neurons.
“Before, we thought serotonin was probably involved. Now we know that serotonergic neurons are definitely involved,” said Vanderbilt’s Douglas McMahon, Ph.D., who supervised the study.
Importantly, when mice born in summer light cycles were switched to winter light cycles the increased firing of serotonin neurons persisted for several months, into adulthood for the mice.
“This showed that early life seasonal photoperiods can have enduring effects on the serotonin neurons. If such an effect occurs in humans, and is long-lasting, it could contribute to the season of birth modulation of SAD risk,” said McMahon, who holds the Stevenson Chair in Biological Sciences at the university.
The findings are published in the journal Current Biology.
Source: Vanderbilt University