Restless REM Sleep May Contribute to Mood, Anxiety Disorders

Batya Swift Yasgur, MA, LSW

July 24, 2019

Restless rapid eye movement (REM) sleep impedes emotional processing, which may contribute to mood and anxiety disorders, new research suggests.

A team of Dutch investigators used fMRI to scan the brains of participants who underwent a stressful experience — in this case, hearing themselves sing out of tune. Brain activity was measured using electroencephalography (EEG).

The next morning, after spending the night in a sleep laboratory, participants were subjected to the same unpleasant experience. Those who had experienced REM sleep were less distressed, whereas those with restless REM sleep were once again upset.

"For now, there is no instant solution, no magic pill" for restless REM sleep, study investigator Eus J. W. Van Someren, PhD, head of the Department of Sleep and Cognition, the Netherlands Institute of Neuroscience, Amsterdam, told Medscape Medical News.

However, the current findings may point to a way of solving the problem, he added.

"Since REM sleep and restlessness are both more likely to occur at the end of the night, it may be good to advise people with insomnia and/or mental problems not to stay in bed too long in the morning — and restrict the time in bed to no more than 7 hours, or even less," he said.

The findings were published online July 11 in Current Biology.

"Siren of the Brain"

The amygdala initially activates during a distressing experience, but subsequent neuronal network reorganization facilitated by REM sleep inhibits the distress if the experience recurs.

Restless REM sleep characterizes several psychiatric disorders, the authors note.

Van Someren described the amygdala as the "siren of the brain," which is set off during times of distress.

REM sleep can help silence this siren, allowing "a time window for reactivation and reorganization of the neuronal circuits that were activated during the initial emotional experience," said Van Someren.

"We had noticed before that people with insomnia have difficulties shedding distress caused by bad emotional experiences and, as a result, can suffer from them for days, weeks, months, or years. We wanted to find out why exactly this would be the case," he added

The researchers assessed 29 adults (mean age, 41.6 years; 52% women) who had insomnia that ranged widely in severity, from an absence of insomnia complaints to meeting criteria for insomnia disorder.

One week prior to the study, participants received an intake interview, structural MRI scans, and audio recordings of themselves singing lyrics accompanying karaoke music.

Investigators used fMRI to record the limbic response of participants induced by the "self-conscious emotional distress" of listening to their own out-of-tune singing.

Van Someren, who was a professional musician, recalled "the embarrassment of listening to one's own [out of tune] singing or playing."

Shame and Embarrassment

Participants also underwent odor-discrimination testing to evaluate whether they fulfilled the prerequisite for differential conditioning, such as capacity to differentiate odors later linked to their own singing stimuli (known as US+) and the singing stimuli of others (known as US–).

"The odor itself was not unpleasant but was used for TMR [targeted memory reactivation], since an odor presented during an experience, such as learning or emotion, will condition that experience," Van Someren said.

The unpleasant experience was associated with an odor that was disseminated while participants slept. Only those with sufficient odor discrimination capacity (n = 13; 54% men; mean insomnia severity index, 11.1) were exposed to odors during sleep for TMR.

Exposure to the unpleasant experience (out-of-tune singing) was repeated after a night of sleep "to quantify reactivity adaptation across the night." EEG was recorded during sleep to determine sleep stages and cortical arousal.

Emotions most reported by participants after listening to their own out-of-tune singing of karaoke fragments were shame and embarrassment.

There were significant blood-oxygen-level-dependent signal (BOLD) responses to their own singing stimuli in limbic circuits, including bilateral amygdalae, bilateral medial prefrontal cortex, and the left posterior cingulate cortex.

Mixed-effects linear models showed that TMR-exposed and non-TMR-exposed participants did not differ in subjective emotional intensity ratings at the first session nor in their overnight change (P = .21 and P = .25, respectively).

There were also no significant group differences in either the amygdala BOLD response during the first session or in its overnight change.

Amygdala reactivity decreased overnight (β = –0.09, P = .001) in proportion to the total duration of consolidated REM sleep (β = –0.12, P = .01).

A significant interaction with the total duration of REM episodes indicated that longer-lasting TTR episodes boosted the effect of subsequent REM episode duration on the overnight decrease in amygdala reactivity.

By contrast, in restless REM sleep, overnight amygdala activation was impeded and was less supportive of the overnight decrease in amygdala activity (β = .013, P = .04).

Interrupted Sleep, Lost Benefit

The effect of REM sleep on overnight adaptation of amygdala reactivity to own-singing stimuli increased with both the total number and integrated activity of spindles during TTR episodes (P = .003 and .006, respectively).

When the out-of-tune singing was replayed the next day, participants with more REM sleep experienced less activation of the amygdala compared with those who had restless REM sleep. The latter group's reactivity was actually increased.

"The more restful REM sleep a person had, the better the overnight adaptation of the amygdala," said Van Someren.

By contrast, "in people with restless REM sleep, the second distressing experience still was very distressful, and the amygdala continued to be activated," he said.

"The effect of REM sleep on amygdala adaptation was enhanced if preceding episodes of TTR sleep were of longer duration, contained more spindles, or showed higher total integrated spindle activity," the investigators write.

However, the effect is counteracted if REM episodes have "abundant interruptions, up to the point that the benefit of REM sleep is completely lost," they add.

These findings "underscore the importance of an integrated approach to the functional role of sleep," they write.

Both restless REM sleep and a hyperactive amygdala are common in individuals with insomnia, posttraumatic stress disorder (PTSD), depression, or an anxiety disorder. It affects "no less than two thirds of people with a mental disorder," Van Someren said.

"We hypothesize that restless REM sleep may transdiagnostically contribute to the fact that people with PTSD carry their traumatic experience to the next day, people with an anxiety disorder their greatest fears, people with depression their despair, and people with chronic insomnia their tension," he said.

"Pay Attention" to Sleep

Commenting for Medscape Medical News, Philip Gehrman, PhD, associate professor, Sleep Neurobiology and Psychopathology Laboratory, Department of Psychiatry and Penn Sleep Center, University of Pennsylvania, Philadelphia, called the study "really interesting, strong, and well done, fitting very nicely with our current thinking" about the function of sleep in emotional health.

Gehrman, who was not involved with the research, said there has been a long-standing attitude in psychiatry and behavioral health that sleep problems are secondary to anxiety and depression. "But that attitude is changing," he noted.

By directly treating and targeting sleep problems in these patients, "you may not only get improvement in sleep but you may also augment the treatment for whatever their comorbid conditions are," Gehman said.

"The take-home message is to pay attention" to a patient's sleep patterns, he added.

The investigators note that "chronically perturbed REM sleep" has previously been found to be a result of early childhood adversity in patients with insomnia disorder and in individuals with PTSD.

"Addressing overnight emotional memory processing deficits in these disorders is likely to provide clues to the mechanisms underlying hyperarousal, which have so far remained enigmatic," they write.

The study was supported by grants from ZONMW Neuropsychoanalysis Fund of the Netherlands Organization of Scientific Research, the Bial Foundation, and the European Research Council. Van Someren has reported no relevant financial relationships.

Curr Biol. Published online July 11, 2019. Abstract

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