By: Stephanie Pappas, LiveScience Senior Writer
Published: 05/13/2013 03:04 PM EDT on LiveScience
Disrupted sleep is so commonly a symptom of depression that some of the first things doctors look for in diagnosing depression are insomnia and excessive sleeping. Now, however, scientists have observed for the first time a dysfunctional body clock in the brains of people with depression.
People with major depression, also known as clinical depression, show disrupted circadian rhythms across brain regions, according to a new study published today (May 13) in the journal Proceedings of the National Academy of Sciences. Researchers looked at post-mortem brain samples from mentally healthy donors and compared them with those of people who had major depression at the time of their death.
They found that gene activity in the brains of depressed people failed to follow healthy 24-hour cycles.
"They seem to have the sleep cycle both shifted and disrupted," said study researcher Jun Li, a professor of human genetics at the University of Michigan. [5 Things You Must Know About Sleep]
The clockwork body
Everyone is born with a genome that acts as a blueprint for building the proteins that make up the body. But genes aren't stable protein-building machines. Instead, they vary in their activity levels, expressing themselves more or less depending on the situation. One factor that influences gene expression is the daily light cycle.
In particular, cells in a region deep in the brain called the hypothalamus act as pacemakers, setting the body clock and keeping cells in the rest of the body on an approximately 24-hour cycle. The pacemaker cells explain why jet lag is such a pain: It takes time for this body clock to readjust in a new time zone.
To better understand how gene expression varies in depressed people, Li and his colleagues looked at the brains of 35 patients with major depression, and 55 mentally healthy people, all of whom had died at various points around the clock. The donated brains contained the fingerprint of gene expression at each time of death. Researchers examined this gene expression in six major brain regions: The dorsolateral prefrontal cortex, the amygdala, the cerebellum, the anterior cingulated cortex, the nucleus accumbens and the hippocampus.
In healthy people, a cycle clearly appeared. Those who had died around the same time of day showed similar patterns of gene expression across the brain.
"Some genes go high, low and high across the day," Li told LiveScience. "Others would be low, high and low."
The patterns were so clear that the researchers could look at the gene expression in a brain and use the information to pinpoint time of death -- but only in healthy brains. The depressed brains didn't follow the healthy patterns.
For example, in healthy people, of the 16 genes that showed the clearest patterns of cycling, 11 genes cycled around the clock in four or more brain regions. By contrast, in people with major depression, only two of these genes showed clear cycling pattern in more than one region, and none cycled in more than three regions.
This lack of evidence of cellular cycling in depressed brains could have indicated that the depressed people's circadian rhythms were simply flattened out, Li said. Or, the lack of pattern could reveal a shift in the daily cycle such that the patterns weren't detectable in the depressed brains.
To test the idea, the researchers compared gene expression in depressed patients who died at different times, and found some similarities. That suggests that the depressed people's body clocks may have been shifted by several hours, the researchers said.
Another analysis, however, found that genes that would be expected to shift together didn't do so in depressed people. That finding suggested that the clocks were disrupted.
In other words, Li said, the problem in depressed brains appears to be both shifting and disruption.
"They seem to be sleeping at the wrong time of the day, and the quality of their sleep is also different from healthy sleep," he said.
The sleep-cycle shift held in patients who had a diagnosis of major depression but who had not taken antidepressants before death, the researchers found, suggesting that it's the disease itself and not the treatment that causes the circadian rhythm problems.
Already, symptoms of insomnia and excessive sleep in depressed people have inspired treatments such as light therapy to try to reset the body clock, Li said. The new research is confirmation that such approaches could work. Researchers might also be able to develop drug treatments to fix the body clock, he said.
"This reinforces the old idea that trying to address sleep cycle is a good practice in diagnosis and in treatment," Li said.
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...Increase Stroke Risk
Even without the typical risk factors, like being overweight or having a family history, short sleep can up your risk for stroke, according to 2012 research. Adults who regularly slept fewer than six hours a night had <a href="http://www.huffingtonpost.com/2012/06/11/sleep-stroke-risk_n_1586837.html">four times the risk of stroke symptoms</a>, HuffPost reported.
...Lead To Obesity
Too little sleep can spur some less-than-ideal food choices, including <a href="http://www.huffingtonpost.com/2013/02/25/sleep-portion-sizes-deprivation-food-calories_n_2735497.html">serving yourself larger portions</a>, and a hankering for junk food, thanks to some complicated hormonal changes that occur when you don't get sufficient shuteye. It seems that six hours of sleep or less <a href="http://www.huffingtonpost.com/2012/10/26/sleep-deprivation-obesity-leptin-ghrelin-insulin_n_2007043.html">bumps up production of the hunger hormone ghrelin</a> and limits leptin, which helps you balance your food intake, according to a 2012 review of 18 studies of sleep and appetite.
...Up Diabetes Risk
A pair of small studies from 2012 examined the link between poor sleep and insulin resistance, a telltale risk factor for diabetes. One found that among healthy teenagers, the <a href="http://www.huffingtonpost.com/2012/10/03/sleep-insulin-resistance-teens_n_1929374.html">shortest sleepers had the highest insulin resistance</a>, meaning the body is <a href="http://diabetes.niddk.nih.gov/dm/pubs/insulinresistance/#resistance">not using insulin effectively</a>, according to the National Institute of Diabetes and Digestive and Kidney Diseases. The second study examined fat cells, in particular, and found that cutting back on sleep <a href="http://annals.org/article.aspx?articleid=1379773">increased insulin resistance in these cells</a>, even when <a href="http://news.health.com/2012/10/15/sleep-deprivation-insulin-resistance/">diet and calorie intake were restricted</a>, Health.com reported.
...Fuel Memory Loss
You probably know that on the days when you are most tired, you're forgetful and unfocused -- but sleep deprivation can lead to <a href="http://www.sciencedaily.com/releases/2013/01/130127134212.htm"><em>permanent</em> cognitive issues</a>. The less we sleep, the less we benefit from the memory-storing properties of sleep. But additionally, a lack of sleep can cause <a href="http://www.huffingtonpost.com/2013/01/28/sleep-deprivation-memory-loss_n_2566999.html">"brain deterioration,"</a> according to a 2013 study, which may at least in part explain memory loss in seniors.
At least in rats, long-term <a href="http://ebm.rsmjournals.com/content/237/9/1101.full">sleep deprivation seems to contribute to osteoporosis</a>, according to a 2012 study. Researchers found <a href="http://www.huffingtonpost.com/2012/09/26/sleep-deprivation-bones-marrow_n_1898610.html">changes to bone mineral density and bone marrow</a> in the rodents when they were deprived of shuteye over a period of 72 days. "If true in humans, and I expect that it may be, this work will have great impact on our understanding of <a href="http://www.eurekalert.org/pub_releases/2012-09/sfeb-los_1091812.php">the impact of sleep deprivation on osteoporosis</a> and inability to repair bone damage as we age," Steven R. Goodman, Ph.D., editor-in-chief of Experimental Biology and Medicine, said in a statement.
...Increase Cancer Risk
A small (but growing) body of research suggests that short and poor sleep can up risk for certain types of cancer. A 2010 study found that among 1,240 people screened for colorectal cancer, the 338 who were diagnosed were <a href="http://onlinelibrary.wiley.com/doi/10.1002/cncr.25507/abstract">more likely to average fewer than six hours of sleep</a> a night. Even after controlling for more traditional risk factors, polyps were more common in people who slept less, according to the study. Getting just six hours of sleep a night has also been linked to an <a href="http://www.huffingtonpost.com/2012/09/06/sleep-breast-cancer-aggressive-deprivation_n_1854658.html">increase of recurrence in breast cancer patients</a>. The study's author has pointed to more and better sleep as a possible pathway of reducing risk and recurrence.
...Hurt Your Heart
The stress and strain of too little sleep can cause the body to produce more of the chemicals and hormones that can lead to heart disease, according to 2011 research. The study found that people who slept for six hours or less each night and have problems staying asleep had a 48 percent <a href="http://www.sciencedaily.com/releases/2011/02/110208091426.htm">higher risk of developing or dying from heart disease</a>.
It's not just heart problems that can lead to sleep-deprivation-related death. In fact, <a href="http://healthland.time.com/2010/09/02/lack-of-sleep-can-cause-depression-weight-gain-and-even-death/">short sleepers seem to die younger</a> of any cause than people who sleep about 6.5 to 7.5 hours a night, TIME reported. A 2010 study examined the impact of short sleep on mortality and found that <a href="http://www.journalsleep.org/ViewAbstract.aspx?pid=27894">men who slept for less than six hours of sleep a night were four times more likely</a> to die over a 14-year period. The study's authors called this link "a risk that has been underestimated."