sleep

Getting enough sleep is widely considered crucial to our well-being. However, for some individuals with Autism, getting enough quality sleep is not as easy as it sounds. Autism Spectrum Disorder (ASD) is a developmental disorder that widely affects the U.S. population, as 1 in 36 children aged eight has been diagnosed with autism (CDC, 2023). The kind and severity of the symptoms that individuals with ASD may exhibit can vary along the ASD spectrum. Sleeping, in particular, is a common challenge for those with ASD, as many suffer from problems related to the REM (Rapid Eye Movement) sleep phase, a phase critical for memory consolidation (Devnani & Hedge, 2015). This can quickly become a vicious cycle for some, as lack of sleep can increase the severity of other Autism-related symptoms but also affect both the individual and the quality of life of their family or caretakers.

To investigate possible treatments, a recent study by Malow et al. focuses on the pharmacological approach of using melatonin to treat sleep disorders. Melatonin is a hormone produced by the body’s pineal gland to regulate circadian rhythm, allowing the body to relax according to the appropriate light-darkness cycles of the day. This study uses a small, long-release tablet (PedPRM) used to mimic endogenous melatonin secretion. It focused mainly on a younger population, from children to adolescents, who met two criteria. The first was that they had confirmed diagnoses of either Autism or Smith-Magenis syndrome and had also experienced sleep abnormalities. Smith-Magenis syndrome is also a developmental disorder that involves symptoms similar to those of ASD, affecting behavior, cognition, and sleep. They also had to have not previously seen improvements when using sleep hygiene treatments to be included in the study, such as establishing a strict bedtime routine and taking steps to provide a calm and comfortable sleep environment (CHOC, 2023).

With the study sample set, the study was conducted over 108 weeks and divided into four phases (Graph I). Throughout the four phases, participants’ caregivers would document sleep quality and total sleep time in a sleep and nap diary to record the efficacy of treatment. The study participants started the first stage with a 2-week period in which they were given placebos. If participants showed improvement while receiving a placebo, they would be removed from the study to reduce the possibility of external factors affecting the results (Scott et al., 2021). After clearing Phase 1, participants entered the second phase, which consisted of a double-blinded 13-week period in which they were randomly placed into either a placebo or treatment group (PedPRM). After this, Phase 3 comprised a longer 91-week open-label period in which both groups were combined. For the final phase of the study, participants were placed again in a 2-week single-blind placebo period to ensure that the drug had been completely removed from the participants with no adverse effects after stopping treatment.

Upon concluding the experimental period, the results to be considered for this study could be divided into three groups: participants’ sleep quality, caregivers’ well-being, and the participants’ growth development. With this data, the researchers found a significant

decrease in sleep disturbance (Graph II-A) and an increase in caregiver satisfaction (II-B) and quality of life (II-C). These were most pronounced during the first half of the treatment. In the latter half of treatment, sleep disturbance continued to decrease but at a slower pace than the initial treatment phase. Fortunately, there were no reported deaths, and most adverse reactions included daytime fatigue and mood swings. However, the severity and extent of these were not detailed in the results of the study and offer the potential to be analyzed further.

The study shows compelling initial evidence that PedPRM is an effective treatment for sleep disorders in individuals with ASD. However, as noted by the researchers, it also shows that constant active treatment is required as most sleep quality improvements are removed upon halting treatment. Since medications for children are generally more strictly controlled, PedPRM consistently demonstrates a possibility for effective pediatric treatment, even if for long-term medication. In particular, these findings are essential as it has been found that rapid-release melatonin is not helpful with maintaining sleep a couple of hours after administration, and it had long been considered a challenge to find small, swallowable prolonged-release tablets for children (Fliesler, 2022). As sleep interruption is something that mainly affects those with neurodevelopmental disorders, this is a significant step towards adequate treatment. However, it is essential to note that this pharmacological alternative should only be considered if behavioral interventions and sleep hygiene modifications have been attempted but have been found unsuccessful.

Sources

CDC. (2022, December 9). Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/autism/facts.html

CDC Newsroom. (2016, January 1). CDC. https://www.cdc.gov/media/releases/2023/p0323-autism.html

CHOC – Children’s Hospital of Orange County. (2023, March 2). Autism and Sleep Hygiene – Children’s Hospital of Orange County. Children’s Hospital of Orange County. https://www.choc.org/programs-services/autism-neurodevelopmental/co-occurring-conditions-program/autism-and-sleep/

Devnani, P., & Hegde, A. U. (2015). Autism and sleep disorders. Journal of Pediatric Neurosciences, 10(4), 304. https://doi.org/10.4103/1817-1745.174438

Fliesler, N. (2022, June 13). Melatonin for kids: Is it effective? Is it safe? – Boston Children’s Answers. Boston Children’s Answers. https://answers.childrenshospital.org/melatonin-for-children/#:~:text=There%20is%20some%20evidence%20to,the%20ability%20to%20swallow%20capsules.

Furfaro, H. (2023, March 10). Sleep problems in autism explained. Spectrum | Autism Research News. https://www.spectrumnews.org/news/sleep-problems-autism-explained/

Lemoine, P., Garfinkel, D., Laudon, M., Nir, T., & Zisapel, N. (2011). Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal. Therapeutics and Clinical Risk Management, 301. https://doi.org/10.2147/tcrm.s23036

Malow, B. A., Findling, R. L., Schröder, C., Maras, A., Breddy, J., Nir, T., Zisapel, N., & Gringras, P. (2021b). Sleep, Growth, and puberty after 2 years of Prolonged-Release Melatonin in children with Autism Spectrum Disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 60(2), 252-261.e3. https://doi.org/10.1016/j.jaac.2019.12.007

Scott, A., Sharpe, L., Quinn, V. F., & Colagiuri, B. (2022). Association of single-blind placebo run-in periods with the placebo response in randomized clinical trials of antidepressants. JAMA Psychiatry, 79(1), 42. https://doi.org/10.1001/jamapsychiatry.2021.3204

Signs & Symptoms | Autism Spectrum Disorder (ASD) | NCBDDD | CDC. (2023, January 11). Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/autism/signs.html

When our bodies shut down at night, our brains transport us into strange, convoluted alternate realities. Dreams range from the mundane to the fantastical, from classrooms to castles. Despite the sheer absurdity of many dreams, they always feel real. But where do dreams even come from, and why do we have them?

Definitions of a dream range from the generous “subjective experience during sleep” to the more specific “immersive spatiotemporal hallucination” (Siclari et al., 2020). Taken either way, dreams are characterized by increased blood flow to regions of the brain called the amygdala, hippocampus, and anterior cingulate cortex. The significant role that these regions play in regulating our emotions may explain the intense emotional aspect of many dreams (Schwartz & Maquet, 2002).

There are five stages of sleep. The first four stages are collectively categorized as non-Rapid Eye Movement, or NREM, sleep. Accordingly, the fifth stage is referred to as the REM stage. During REM sleep, our eyeballs flit back and forth underneath our eyelids, our muscles are paralyzed to prevent self-injury from dream enactment, and our brain activity reflects that of wakefulness (Siclari et al., 2020). Although dreams are more common in REM sleep, recent research has shown that shorter and less bizarre dreams occur during NREM sleep as well (Nielsen, 2000).

It seems like something as peculiar as dreaming should have a distinct purpose. However, the exact function of dreams is still unknown. One theory speculates that dreams are simply a byproduct of other brain activity, such as memory consolidation, that occurs during sleep. Sigmund Freud, oft-considered the father of psychology, believed that dreams allowed for the disguised fulfillment of the sexual and aggressive desires of the id. According to Freud, the id is the component of our personality that lies below our consciousness and drives primitive, aggressive desires. Other theories suggest that dreaming is evolutionarily advantageous because it allows us to practice behaviors important to our survival in our sleep, preparing us for the same events in wakefulness. These behaviors include hunting, mating, responding to threats, and socializing (Siclari et al., 2020).

Some people seem to remember their dreams every night, while others claim to never dream at all. Dream recall averages at about one dream a week, but this varies widely. Practices such as keeping a dream journal and setting an alarm during a period of likely REM sleep improve recall.

Recall is inherently easier with nightmares. By definition, nightmares cause awakening, while “bad dreams” contain similar emotionally troubling content but do not induce awakening (Robert & Zadra, 2014). There is evidence for a genetic predisposition to nightmares (Hublin et al., 1999).

Lucid dreams are a fascinating type of REM dreaming in which the individual is aware they are dreaming and may even be able to control the dream. Lucid dreams activate brain areas usually associated with insight and agency in wakefulness (Dresler et al., 2012). They also elicit the same eye movements and respiration patterns. For example, when asked to dive into a pool in their lucid dream, subjects briefly stopped breathing — as if they were underwater. The perception of time is also similar; counting from 0 to 10 in a lucid dream takes about as long as it does in real life. Lucid dreams provide particularly valuable insights into the mechanisms of dreaming because the dreamer can communicate with the researcher through pre-determined eye movements (Erlacher et al., 2014).

So what happens when we miss out on REM sleep and REM dreams? Unfortunately, modern society gives us plenty of chances to find out. Substances, especially alcohol and marijuana, decrease the time we spend in REM sleep. Medications such as benzodiazepines, antidepressants, and, ironically, sleeping pills also decrease REM sleep. Furthermore, exposure to artificial light before bed and the use of an alarm clock limit REM sleep. Collectively, the impact of these behaviors can hinder immune function, memory consolidation, and mood regulation (Naiman, 2017).

Despite everything that scientists have discovered about dreams, there is still much about them that remains a mystery. Recently, researchers have been trying to interpret the content of dreams by using brain scans and machine learning to decode certain patterns of brain activity (Horikawa et al., 2013). For now, however, we can only take what we do know and marvel at the rest. Every night brings its own all-expenses-paid adventure into another reality.

References

Dresler, M., Wehrle, R., Spoormaker, V. I., Koch, S. P., Holsboer, F., Steiger, A., Obrig, H., Sämann, P. G., & Czisch, M. (2012). Neural Correlates of Dream Lucidity Obtained from Contrasting Lucid versus Non-Lucid REM Sleep: A Combined EEG/fMRI Case Study. Sleep, 35(7), 1017–1020. https://doi.org/10.5665/sleep.1974

Erlacher, D., Schädlich, M., Stumbrys, T., & Schredl, M. (2014). Time for actions in lucid dreams: Effects of task modality, length, and complexity. Frontiers in Psychology, 4, 1013. https://doi.org/10.3389/fpsyg.2013.01013

Horikawa, T., Tamaki, M., Miyawaki, Y., & Kamitani, Y. (2013). Neural Decoding of Visual Imagery During Sleep. Science, 340(6132), 639–642.

Hublin, C., Kaprio, J., Partinen, M., & Koskenvuo, M. (1999). Nightmares: Familial aggregation and association with psychiatric disorders in a nationwide twin cohort. American Journal of Medical Genetics, 88(4), 329–336. https://doi.org/10.1002/(SICI)1096-8628(19990820)88:4<329::AID-AJMG8>3.0.CO;2-E

Naiman, R. (2017). Dreamless: The silent epidemic of REM sleep loss. Annals of the New York Academy of Sciences, 1406(1), 77–85. https://doi.org/10.1111/nyas.13447

Nielsen, T. A. (2000). A review of mentation in REM and NREM sleep: “Covert” REM sleep as a possible reconciliation of two opposing models. Behavioral and Brain Sciences, 23(6), 851–866. https://doi.org/10.1017/S0140525X0000399X

Robert, G., & Zadra, A. (2014). Thematic and Content Analysis of Idiopathic Nightmares and Bad Dreams. Sleep, 37(2), 409–417. https://doi.org/10.5665/sleep.3426

Schwartz, S., & Maquet, P. (2002). Sleep imaging and the neuro-psychological assessment of dreams. Trends in Cognitive Sciences, 6(1), 23–30. https://doi.org/10.1016/S1364-6613(00)01818-0

Siclari, F., Valli, K., & Arnulf, I. (2020). Dreams and nightmares in healthy adults and in patients with sleep and neurological disorders. The Lancet Neurology, 19(10), 849–859. https://doi.org/10.1016/S1474-4422(20)30275-1