Megan Brooks

December 06, 2011

December 6, 2011 (Waikoloa, Hawaii) — Sleep-deprived laboratory rats show significant changes in brain structure and chemical responses that look very similar to those observed in depressed adults, according to research reported here at the American College of Neuropsychopharmacology (ACNP) 50th Annual Meeting.

"Disrupted sleep has traditionally been viewed as a symptom of mood disorders like depression," Peter Meerlo, PhD, from the Center for Behaviour and Neurosciences, University of Groningen, the Netherlands, who led the study, told reporters attending a press briefing.

Yet, "gradually, data are accumulating that suggest that perhaps, at least in some patients, disturbed sleep may actually be a causal factor in depression," Dr. Meerlo said.

The scientists restricted a group of healthy rats to 4 hours of sleep per day, which is considerably less than they would normally get in the laboratory. The researchers assessed how sleep loss affects several neural circuits and chemical responses known to be associated with depression.

One day of sleep restriction "didn't seem to have a dramatic effect," Dr. Meerlo reported, "but when we continued this schedule of restricted sleep, we saw gradual changes over 1 week and 1 month."

One week of sleep restriction altered hypothalamic-pituitary-adrenal axis regulation and reduced hippocampal cell proliferation. After 1 month of sleep restriction, there was evidence of a significant reduction in hippocampal volume; "we actually saw morphological changes," Dr. Meerlo commented.

"Striking" Finding

Sleep-deprived rats were also less sensitive to serotonin, which is strongly involved in the regulation of emotions. "We tested that by directly injecting a serotonergic agent and then looking at hormone, temperature, and behavioral responses that are regulated by serotonin," Dr. Meerlo explained.

"In sleep-restricted rats, many of these responses were diminished as compared to control rats that could sleep as much as they want," he added.

Another important and "striking" finding, said Dr. Meerlo, was the time it took for the rats to recover. After 1 week of restricted sleep, they needed almost a week of adequate sleep before the changes in the serotonergic system normalized.

This may suggest that trying to "catch up" on lost sleep by sleeping more during the weekend may not be sufficient.

"At the end of the weekend, you may feel that you have recovered, but there may actually be traces in the brain of the preceding period of sleep restriction," said Dr. Meerlo.

Altogether, these findings provide "strong support" for the idea that restricted or disrupted sleep may not just be a symptom of mood disorders but "actually may be a causal factor in developing depression," Dr. Meerlo said.

Sleep, Depression "Intimately Linked"

Commenting on the study for Medscape Medical News, Noah S. Philip, MD, assistant professor in the Department of Psychiatry and Human Behavior (Clinical), Alpert Medical School of Brown University, Providence, Rhode Island, described the investigation as a "very interesting study from several perspectives."

"Disrupted sleep is classically thought of as a hallmark neurovegetative symptom of depression, but this and other research indicates the relationship between depressive symptoms and sleep is much more complicated," Dr. Philip explained.

"This is of particular importance in the depression literature, as several of the available antidepressants are shown to disrupt sleep architecture, indicating they can cause poorer sleep."

This study "elegantly" shows a neurotoxic effect of sleep deprivation (ie, changes in hippocampal size). This effect has been seen in several psychiatric disorders, including depression and posttraumatic stress disorder (PTSD), Dr. Philip noted.

"PTSD also is characterized by sleep impairment, which makes sense if you think of sleep deprivation as a chronic stress situation," he added.

"As with any preclinical study, it is important to remember that these experiments should be replicated in humans to measure the validity of their effects," Dr. Philip cautioned. "However, taken together with the available literature, this study advances the concept that sleep and depression are intimately linked together, and that future therapeutics designed to target both sleep and depression is an area of important research."

Dr. Meerlo and Dr. Philip have disclosed no relevant financial relationships.

American College of Neuropsychopharmacology (ACNP) 50th Annual Meeting. Presented December 6, 2011.

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