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A study of sleep disturbance in children with autism spectrum disorder (ASD) found that circadian pathway and insomnia risk genes may play a role in ASD liability, but have minimal impact on sleep disturbance.

Because problems with sleep have been reported in 40% to 80% of children with ASD beginning in infancy and lasting throughout the lifespan, the researchers were curious about the role of copy number variants (CNVs) for genes linked to insomnia risk and circadian pathway, hypothesizing that ASD was linked to genomic variants disrupting pathways involved in insomnia and circadian rhythms. Rackeb Tesfaye and colleagues also looked at sleep disturbances in this patient population. Tesfaye is a PhD researcher at McGill University, Montreal Neurological Institute, Azrieli Centre for Autism Research, Montreal, Canada.

To test their hypothesis, Tesfaye et al analyzed 2 cohort datasets, which included 2569 simplex families with 1 ASD proband each and 2851 unaffected siblings and 3426 probands with ASD from multiplex families from the general population.

Tesfaye et al identified 335 rare circadian genes and 616 rare insomnia risk genes. They noted that duplications and deletions with circadian genes were overrepresented in the ASD probands in comparison to siblings and unselected controls. In insomnia risk genes, only deletions—not duplications—were associated with ASD in both cohorts, with results remaining significant after the researchers adjusted for cognitive ability. CNVs with insomnia risk and circadian pathway genes were more strongly associated with ASD in comparison to CNVs with other genes, and circadian genes did not influence either insomnia traits or sleep duration in individuals with ASD.

“Our findings provide evidence for the contribution of circadian pathway dysfunction to ASD, but the mechanisms by which these genes increase ASD risk are unknown,” Tesfaye and colleagues wrote. “Previous theories have put forth sleep disturbance as a causal factor for ASD risk and other psychopathologies… However, in this study, the limited effects of circadian genes on sleep duration and insomnia are unlikely to disrupt behavior and cognition enough to increase ASD risk. Instead, we propose that circadian pathway genes increase ASD risk with minimal to no modulation of sleep duration and insomnia.”

The researchers noted that further research in this area is needed in order to replicate their findings in similar and larger-scale studies.

 “Future studies investigating the combined effect of genomic variants and environmental factors on sleep measures, behavioral traits, and brain architecture are needed for a holistic understanding of the interplay between genes, sleep, and ASD,” they concluded.

1. Tesfaye R, Huguet G, Schmilovich Z, et al. 

Investigating the contributions of circadian pathway and insomnia risk genes to autism and sleep disturbances

Connections between autism risk, sleep disturbances, insomnia risk genes and circadian pathways were analyzed.

Study Explores Impact of Circadian Pathway, Insomnia Risk Genes on Sleep Disturbance in Autism

 covered a wide variety of psychiatric issues and industry updates, from the psychiatric implications of the Parkland School mass shooting to what psychiatrists need to know about herbal medicine. Here are some highlights from the week.

App Intervention May Reduce Insomnia in Health Care Workers

Researchers studied an app-based Yoga of Immortals (YOI) intervention on the mental health of health care workers, including sleep disruption, and found that it produced a measurable benefit. There is a need to help health care workers with sleep trouble, as recent literature suggests that approximately 38% experienced insomnia during the COVID-19 pandemic.

“There is a compelling societal interest in developing interventions targeting the emotional needs of health care workers who are facing a public health crisis,” wrote Currie et al.

The YOI intervention teaches specific practices based on ancient yogic teachings and the 3 core components of the YOI program—breathwork, whole body movements, and postures—have multiple emotional benefits. 

On my most recent flight home (I know, I usually end up writing a new article every time I fly), I sat next to a middle-aged woman and her father who seems to be struggling with some kind of cognitive impairment, possibly dementia. I was very impressed with how, throughout our 2.5-hour long flight, that she was quite attentive to his every need and kept him both engaged and entertained. She did that through asking questions and sharing pictures saved on her phone that seemed to fill his soul with joy. 

The Parkland School Mass Shooting and Its Psychiatric Implications

Coincidentally, around the same time as the Sandy Hook School shooting trial of Alex Jones ended, a trial about the Parkland School mass shooting ended. We discussed some of the psychological implications of the former in Friday’s column, “The Psychological Heroism of the Sandy Hook Families.” Today we will primarily cover Parkland, with an added overall perspective on mental dysfunction and crime.

In the Parkland School trial, the major mental health issue seemed to be whether whatever mental health problems the shooter had should influence whether or not he got the death penalty. He did not. 

Herbal Medicine: What Psychiatrists Need to Know

Herbal medicines have been used to treat mental health disorders since ancient times. Many of the medications used in contemporary medicine originated from plants—salicylic acid from the willow tree, for example, and morphine from poppies. Numerous botanical treatments are useful in general psychiatry. This article discusses the most beneficial and commonly used herbal medicines to treat mental health concerns.

Americans spent $11.3 billion on herbal supplements in 2020, which represented a record increase in spending of 17.3% from 2019 to 2020. According to the 2020 COVID-19 consumer survey of the Council for Responsible Nutrition, among those who increased supplement intake, nearly a quarter cited mental health–related reasons, including stress and anxiety. 

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Do you have a comment on any of these or other articles? Have a good idea for an article and want to write? Interested in sharing your perspectives? Write to us at 

From herbal medicine for psychiatrists to the psychiatric implications of the Parkland School massing shooting, here are highlights from the week in Psychiatric Times.

The Week in Review: October 17-21

Research shows that a combination of sleep knowledge and education about sleep can have a substantial impact on a person’s sleep habits. An often underrecognized fact is that healthy sleep habits are not intuitive, and attitudes about sleep vary widely. Inconsistent sleep schedules, sacrificing sleep, poorly timed naps, and use of electronics before sleep are all common habits among individuals of all ages, including those with and without sleep disorders. These habits can lead to consequences like behavioral and emotional issues, even among individuals who do not fit the criteria for a psychiatric diagnosis.

For example, a study assessing parental practices among parents whose children were enrolled in an early child education program showed that 81% of the parents surveyed believed that their children had healthy sleep habits, yet 50% and 33% of the children had unhealthy bedtime practices and insufficient sleep that were not recognized as such by their parents.

 These habits may lead to lifelong sleep problems if parents and children are not provided with the correct information about the importance of sleep and instructed about safe and effective ways to improve sleep quality and quantity.

Older adults often have sleep practices that can be detrimental to emotional and health as well. A large study that included 2312 participants aged 65 and older showed a high prevalence of insufficient sleep that was found to be associated with a sedentary lifestyle and an overall lack of physical activity.

Sleep knowledge and attitudes include several different components. One study conducted at the Department of Psychological Science at the University of North Carolina at Charlotte defined 3 separate components of sleep attitudes:

1) A cognitive component includes a person’s beliefs about the importance and necessity of adequate sleep.

2) An emotional component involves having a positive evaluation of the necessity of sleep.

3) A behavioral component involves taking action to make time for sleep in a person’s schedule.

The study found that participants who reported positive attitudes about sleep also experienced longer sleep duration, better sleep quality, and better sleep hygiene.

 Of these 3 interrelated components, it is the behavioral that has the most definitive impact, as it is a necessary factor in actually achieving adequate sleep. However, most individuals would not take the steps to incorporate the behavioral component in the absence of the cognitive and emotional components, so they are all key factors.

Another study used objective measures tracked by a Fitbit Flex accelerometer for 7 days to assess sleep among a group of 218 college students. Interestingly, while the study also showed that sleep attitudes were directly associated with longer sleep duration and better sleep quality, the researchers found that greater sleep knowledge did not correlate with these outcomes.

 These results suggest that a fundamental comprehension about the benefits of sleep and a baseline knowledge of the effective ways to attain good sleep are not enough to impact a person’s daily sleep habits and sleep outcomes. It appears that the attitudes a person has about sleep play a far greater role than pure knowledge when it comes to influencing behavior.

Of course, a positive attitude about sleep must be paired with accurate knowledge, as even the most well-intentioned patient can potentially attempt to use methods for sleep that are not beneficial. These can include drinking alcohol before bed, which many believe promotes healthy sleep, but can reduce the quality of a person’s sleep. For individuals who do not have sleep problems, interventions to improve sleep can include a variety of strategies, including stress management, relaxation, stimulus control, sleep hygiene, and exercise.

It is not uncommon for people to underestimate the importance of sleep and its impact on health. For instance, workaholism and competitive sleep deprivation are common among highly productive individuals—even health professionals. The outcomes can lead to interpersonal relationship difficulties, and in some instances, may lead to a referral for a psychiatric or psychological evaluation.

Physicians can help promote accurate sleep knowledge and healthy sleep attitudes for patients. Cognitive and behavioral interventions have been shown to have a positive impact on sleep,

 and these interventions can have lasting effects once patients experience an improved quality of life with less daytime fatigue, improved mood, and better productivity after adopting them.

; clinical assistant professor, Case Western Reserve University School of Medicine, Division of Medical Education; and editor in chief emeritus of 

Sleep health literacy in head start families and staff: exploratory study of knowledge, motivation, and competencies to promote healthy sleep

2. Ortolá R, García-Esquinas E, Cabanas-Sánchez V, et al. 

Association of physical activity, sedentary behavior, and sleep with unhealthy aging: consistent results for device-measured and self-reported behaviors using isotemporal substitution models

Association of sleep attitudes with sleep hygiene, duration, and quality: a survey exploration of the moderating effect of age, gender, race, and perceived socioeconomic status

Direct and indirect associations of sleep knowledge and attitudes with objective and subjective sleep duration and quality via sleep hygiene

5. Murawski B, Wade L, Plotnikoff RC, et al. 

A systematic review and meta-analysis of cognitive and behavioral interventions to improve sleep health in adults without sleep disorders

How can knowledge—and positive attitudes—about sleep improve quality of life for patients?

Sleep Attitudes Influence Sleep More than Knowledge

“Sleep problems are understudied,” Ellen Lee, MD, told attendees at the 2021 American Psychiatric Association (APA) Annual Meeting. “They’re underdiagnosed and undertreated in people with mental illness.” Thus, Lee encouraged clinicians to screen for sleep problems, because sleep “is a modifiable and important target for intervention.” Lee, along with other colleagues, shared insights and preliminary research results on how sleep may impact mental health and psychiatric disorders.

Sleep problems affect between 30 and 80% of individuals with schizophrenia and are associated with lower quality of life and poorer cognitive and frontal lobe functioning, explained Lee, assistant professor in residence in the Department of Psychiatry at the University of California at 

 In as-yet unpublished research, Lee found that sleep apnea is associated with increased inflammation, while higher subjective reports of sleep quality are associated with lower levels of inflammation. Since inflammation is also associated with 

 treating sleep problems could also improve the symptoms of mental illnesses.

Beyond schizophrenia, sleep issues also appear in mood disorders like depression. Stephen Smagula, PhD, presented research on possible links between morning activation deficits and depression among family members caring for patients with dementia.

Older individuals with depression often report difficulty getting up and active in the 

 Morning activation deficits are sometimes thought to be immutable (some individuals are just not morning people), but in functional magnetic resonance imaging readings, dementia caregivers with depression showed higher resting-state amygdala-PCC connectivity, which is associated with stress, fear, and 

 “Although this is speculative,” Smagula cautioned, “it seems plausible that the non-morning type caregivers are doing behaviorally disengaged, emotion-focused coping. So put another way, some caregivers might wake up, feel overwhelmed, say ‘Expletive! I’m going back to bed.’”

This raises the possibility, according to Smagula, who is assistant professor of psychiatry and epidemiology at the University of Pittsburg, that “instead of treating the depression and hoping the morning activation deficit goes away, we could be targeting the morning activation deficit to treat the depression.” Clinicians could consider treatments such as activity scheduling, which would get the caregivers up and moving, increase their light exposure, decrease fragmented sleep, and limit the time they spend ruminating—all of which could improve their depressive symptoms.

Sleep also affects cognition, especially in older adults. Ruth O’Hara, PhD, presented initial data on the impacts of delta activity at sleep onset (DASO). Study participants with DASO demonstrated better affective function overall and over time, which led O’Hara to conclude that testing DASO or other variables may help clinicians predict patients’ cognitive futures. “We think that characterizing sleep dysregulation in older adults may in fact identify valuable biomarkers,” explained O’Hara, who is the Josephine Q. Berry Professor of Psychiatry and Behavioral Sciences at Stanford University. They could “help us predict cognitive decline and onset of dementia, as well as predicting affective dysfunction.”

1. Cohrs S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics. 

2. Keshavan MS, Montrose DM, Miewald JM, Jindal RD. Sleep correlates of cognition in early course psychotic disorders. 

3. Bromundt V, Köster M, Georgiev-Kill A, et al. Sleep-wake cycles and cognitive functioning in schizophrenia. 

4. Lee EE, Ancoli-Israel S, Eyler LT, et al. Sleep disturbances and inflammatory biomarkers in schizophrenia: focus on sex differences. 

5. Smagula SF, Capps CS, Krafty RT. Evaluating the timing of differences in activity related to depression symptoms across adulthood in the United States. 

6. Smagula SF, Karim HT, Ibrahim TS, et al. Resting-state function connectivity associated with being a "morning-type" dementia caregiver and having lower depression symptom severity. 

Sleep problems are understudied, underdiagnosed, and undertreated. 

Dreaming of New Treatments

Between mid-February and mid-March 2020, the number of sleep prescriptions in the United States rose by 14.8%. The increase may be due to the pandemic, says Manoj Malhotra, MD. Based on his experience, he says “the current environment, with myriads of shifts in our day-to-day lives, is a perfect storm for sleep challenges.”

In this Mental Health Minute, Malhotra explains how to distinguish between a general lack of sleep and chronic insomnia, and how to treat the latter.

 is vice president, United States medical affairs for the neurology business group at Eisai.

Have you seen more patients with sleep problems during the pandemic? 

Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

Key considerations for healthcare providers seeking to manage their patients’ insomnia.  

The COVID-19 Pandemic Is a Perfect Storm for Sleep Challenges

The US Food and Drug Administration (FDA) recently accepted the new drug application (NDA) for Idorsia’s investigational dual orexin receptor antagonist, daridorexant, designed for the treatment of 

“I’m very happy that this first regulatory hurdle is behind us,” said Jean-Paul Clozel, MD, Chief Executive Officer of Idorsia. “This was a huge NDA and the team has done an excellent job in preparing the dossier, on which the FDA can judge the properties and merits of daridorexant. We now stand-by to work with the FDA to answer any questions that might arise concerning the effect of daridorexant on sleep, daytime functioning, and its safety profile.”

Daridorexant targets overactive wakefulness associated with insomnia by blocking the activity of orexin, has a rapid onset, and lasts long enough to cover the night without any next-morning residual sleepiness. According to data from the phase 3 registration program, daridorexant is the first insomnia treatment to show statistically significant and clinically meaningful improvements in daytime functioning, sustained over time, as well as sleep during the night.

“While we designed daridorexant to have the optimal profile for a sleep medicine, I am none-the-less stunned by the results. Once approved, by providing daridorexant to the millions of patients with insomnia, Idorsia will have a major impact on this medical, social, and economic problem,” Clozel said. “It has struck me particularly in these times of confinement that we are living through, that sleep problems are a major issue and require an extremely safe and effective drug that can be used by the many. With these results Idorsia is entering into a new era; less than 3 years since its creation, Idorsia is taking a huge step forward in delivering on the vision to become a fully-fledged biopharmaceutical company.”

Adverse events included headache, somnolence, fatigue, dizziness, and nausea, although the incidence of somnolence was low and did not increase with daridorexant 50 mg when compared with placebo.

Idorsia submitted the NDA on January 8, 2021 and anticipates a US launch in the first half of 2022, should approval be received.

1. Idorsia Pharmaceuticals. FDA accepts the new drug application for review of Idorsia’s daridorexant for the treatment of adult patients with insomnia. 

https://www.globenewswire.com/news-release/2021/03/10/2190042/0/de/FDA-accepts-the-new-drug-application-for-review-of-Idorsia-s-daridorexant-for-the-treatment-of-adult-patients-with-insomnia.html

2. Idorsia Pharmaceuticals. Idorsia announces positive results in the first Phase 3 study of daridorexant with improved overall sleep and daytime performance of patients with insomnia. News release. April 20, 2020. 

https://www.idorsia.com/media/news-details?newsId=2284972

This investigational dual orexin receptor antagonist improved sleep overnight and daytime functioning. 

Insomnia Treatment Without Daytime Sleepiness

Teralyn Sell, PhD, MS, NCC, LPC, provides tips on what late night snacks could disrupt sleep patterns. 

Blueberries Treat Depression, With a Catch

holds a doctorate in psychology and is the founder of Pro Recovery Rx, a supplement line dedicated to supporting brain health for individuals in addiction recovery. She also teaches a class called NeuroHealth Coach, which helps professionals integrate brain health into their daily lives.

The key to better sleep? Stabilizing blood sugar. 

Goodnight, Sugar: Foods to Improve Sleep

Over 30 million Americans live with diagnosable chronic insomnia. It can impair their everyday functions when awake and affect their mood. Chronic insomnia is also a risk factor for other chronic illnesses and psychiatric disorders (up to 40% also have depressive symptoms).

Existing pharmacological treatments are designed for short-term use, which may not be enough to combat a long-term illness. In this Mental Health Minute, Yuri Maricich, MD introduces Somryst, the first FDA-authorized prescription digital therapeutic (PDT) for treating chronic insomnia. It is a 9-week program that is accessible through mobile devices, including smartphones and tablets. He discusses two studies on the effectiveness of this new PDT.

(Note: in the video, Dr Maricich says that the FDA authorized Somryst in 2023. The FDA authorized it in 2020.)

A new treatment has been found effective for treating a common sleep disorder.

Introducing the First FDA-authorized Prescription Digital Therapeutic for Chronic Insomnia

Dr Richard Bogan discusses the ins and outs of sleep and psychiatric disorders and shares his thoughts about a recent FDA approval of XYWAV (calcium, magnesium, potassium, and sodium oxybates), indicated for the treatment of narcolepsy. XYWAV, 

, is "the first FDA approved new treatment option indicated for both cataplexy and excessive daytime sleepiness in people living with narcolepsy in more than 15 years." 

 is Medical Director, SleepMed of South Carolina; Chief Medical Officer, SleepMed, Inc; Associate Clinical Professor, University of South Carolina School of Medicine; and Associate Clinical Professor, Medical University of South Carolina in Charleston, SC.

A sleep specialist highlights what to watch out for in your patients.

Intersection of Sleep and Psychiatric Disorders

There is overwhelming evidence that sleep and circadian rhythm disturbances and disorders are prevalent in psychiatric patients and associated with worse outcomes. Nonetheless, the associations between sleep/rhythms and psychiatric disorders are not well understood, and additional research is necessary to mechanistically link sleep dysfunction to mental illness. Furthermore, despite the fact that there is evidence that treating sleep and behavioral rhythms improves psychiatric outcomes, training in sleep medicine for psychiatrists is often insufficient. As a result, sleep and rhythms are often not adequately assessed or appropriately targeted in the clinical practice of psychiatry.

The articles in this Special Report address key issues. While the association between insomnia and psychiatric disorders has long been recognized, more recent evidence demonstrated a strong relationship between insomnia and suicidal ideation and behaviors across the lifespan, as discussed by Wilfred R. Pigeon, PhD, and Todd M. Bishop, PhD. Thus, patients with insomnia, even in the absence of severe psychiatric symptomatology, should be screened for suicide, and treatment for insomnia should be considered to reduce suicidal ideation.

Circadian rhythm abnormalities are also prevalent in psychiatric patients, although they have received less attention than sleep problems. Practitioners may not always recognize circadian abnormalities in their patients and may lack the training and knowledge to provide adequate chronotherapy; for example, delayed onset due to a shifted circadian rhythm may be mistaken for sleep onset insomnia if a careful sleep history is not obtained. Helen J. Burgess, PhD, and Leslie M. Swanson, PhD, discuss the association between delayed sleep phase and mood, anxiety and substance abuse, as well as the increased risk of psychiatric illness related to irregular sleep timing. Their expert tips and guidance in screening patients for circadian rhythm abnormalities as well as stabilizing and entraining rhythms with light therapy, melatonin, and behavioral interventions is most useful.

Similarly, the article by Ellen E. Lee, MD, discusses how sleep can affect psychiatric disorders by increasing inflammation and oxidative stress. Her group has shown that patients with serious mental illnesses have increased levels of pro-inflammatory cytokines. Other studies have shown that sleep deprivation, insomnia, and obstructive sleep apnea are not only more common in patients with psychiatric disorders, but they are also associated with worse outcomes and contribute to inflammation. Conversely, treatments for insomnia and sleep apnea have been shown to have positive effects on psychiatric symptomatology. Taken together, these findings suggest mechanistic pathways by which sleep disorders, inflammation, and psychiatric illness are linked.

In summary, there is increasing evidence that disturbed sleep and circadian rhythms impact the risk for developing psychiatric disorders, and inflammatory processes are suggested as one possible mechanism of this well-established relationship. Sleep and circadian rhythm disturbances are modifiable factors, and while data on the effects of sleep disorder treatment on inflammatory processes is preliminary and limited, treating sleep and behavioral activity rhythms have consistently shown positive impact on mental health outcomes. Most importantly, treatment of sleep dysfunction may reduce suicide risk.

Future research is necessary to better understand the mechanistic pathways and to improve the availability of evidence-based treatments of sleep disorders in patients with mental health disturbances. Hopefully this Special Report will help you better understand some of these relationships and will lead to improved patient outcomes.

Dr Benca is Chair of Psychiatry & Human Behavior in the School of Medicine at University of California, Irvine. She reports that she has served as a consultant to Eisai, Genomind, Jazz, and Merck.

The associations between sleep/rhythms and psychiatric disorders are not well understood. With additional research we can better address key issues and improve patient outcomes.

Sleep Deprivation