Sleep difficulties linked to altered brain development in infants who later develop autism
May 7, 2020
Science Daily/University of Washington
Infants spend most of their first year of life asleep. Those hours are prime time for brain development, when neural connections form and sensory memories are encoded.
But when sleep is disrupted, as occurs more often among children with autism, brain development may be affected, too. New research led by the University of Washington finds that sleep problems in a baby's first 12 months may not only precede an autism diagnosis, but also may be associated with altered growth trajectory in a key part of the brain, the hippocampus.
In a study published May 7 in the American Journal of Psychiatry, researchers report that in a sample of more than 400 6- to 12-month-old infants, those who were later diagnosed with autism were more likely to have had difficulty falling asleep. This sleep difficulty was associated with altered growth trajectories in the hippocampus.
"The hippocampus is critical for learning and memory, and changes in the size of the hippocampus have been associated with poor sleep in adults and older children.
However, this is the first study we are aware of to find an association in infants as young as 6 months of age," said lead author Kate MacDuffie, a postdoctoral researcher at the UW Autism Center.
As many as 80% of children with autism spectrum disorder have sleep problems, said Annette Estes, director of the UW Autism Center and senior author on the study. But much of the existing research, on infants with siblings who have autism, as well as the interventions designed to improve outcomes for children with autism, focus on behavior and cognition. With sleep such a critical need for children -- and their parents -- the researchers involved in the multicenter Infant Brain Imaging Study Network, or IBIS Network, believed there was more to be examined.
"In our clinical experience, parents have a lot of concerns about their children's sleep, and in our work on early autism intervention, we observed that sleep problems were holding children and families back," said Estes, who is also a UW professor of speech and hearing sciences.
Researchers launched the study, Estes said, because they had questions about how sleep and autism were related. Do sleep problems exacerbate the symptoms of autism? Or is it the other way around -- that autism symptoms lead to sleep problems? Or something different altogether?
"It could be that altered sleep is part-and-parcel of autism for some children. One clue is that behavioral interventions to improve sleep don't work for all children with autism, even when their parents are doing everything just right. This suggests that there may be a biological component to sleep problems for some children with autism," Estes said.
To consider links among sleep, brain development and autism, researchers at the IBIS Network looked at MRI scans of 432 infants, surveyed parents about sleep patterns, and measured cognitive functioning using a standardized assessment. Researchers at four institutions -- the UW, University of North Carolina at Chapel Hill, Washington University in St. Louis and the Children's Hospital of Philadelphia -- evaluated the children at 6, 12 and 24 months of age and surveyed parents about their child's sleep, all as part of a longer questionnaire covering infant behavior. Sleep-specific questions addressed how long it took for the child to fall asleep or to fall back asleep if awakened in the middle of the night, for example.
At the outset of the study, infants were classified according to their risk for developing autism: Those who were at higher risk of developing autism -- about two-thirds of the study sample -- had an older sibling who had already been diagnosed. Infant siblings of children with autism have a 20 percent chance of developing autism spectrum disorder -- a much higher risk than children in the general population.
A 2017 study by the IBIS Network found that infants who had an autistic older sibling and who also showed expanded cortical surface area at 6 and 12 months of age were more likely to be diagnosed with autism compared with infants without those indicators.
In the current study, 127 of the 432 infants were identified as "low risk" at the time the MRI scans were taken because they had no family history of autism. They later evaluated all the participants at 24 months of age to determine whether they had developed autism. Of the roughly 300 children originally considered "high familial risk," 71 were diagnosed with autism spectrum disorder at that age.
Those results allowed researchers to re-examine previously collected longitudinal brain scans and behavioral data and identify some patterns. Problems with sleep were more common among the infants later diagnosed with autism spectrum disorder, as were larger hippocampi. No other subcortical brain structures were affected, including the amygdala, which is responsible for certain emotions and aspects of memory, or the thalamus, a signal transmitter from the spinal cord to the cerebral cortex.
The UW-led sleep study is the first to show links between hippocampal growth and sleep problems in infants who are later diagnosed with autism.
Other studies have found that "overgrowth" in different brain structures among infants who go on to develop those larger structures has been associated, at different stages of development, with social, language and behavioral aspects of autism.
While the UW sleep study found a pattern of larger hippocampal volume, and more frequent sleep problems, among infants who went on to be diagnosed with autism, what isn't yet known is whether there is a causal relationship. Studying a broader range of sleep patterns in this population or of the hippocampus in particular may help determine why sleep difficulties are so prevalent and how they impact early development in children with autism spectrum disorder.
"Our findings are just the beginning -- they place a spotlight on a certain period of development and a particular brain structure but leave many open questions to be explored in future research," MacDuffie said.
A focus on early assessment and diagnosis prompted the UW Autism Center to establish an infant clinic in 2017. The clinic provides evaluations for infants and toddlers, along with psychologists and behavior analysts to create a treatment plan with clinic- and home-based activities -- just as would happen with older children.
The UW Autism Center has evaluated sleep issues as part of both long-term research studies and in the clinical setting, as part of behavioral intervention.
"If kids aren't sleeping, parents aren't sleeping, and that means sleep problems are an important focus for research and treatment," said MacDuffie.
The authors note that while parents reported more sleep difficulties among infants who developed autism compared to those who did not, the differences were very subtle and only observed when looking at group averages across hundreds of infants. Sleep patterns in the first years of life change rapidly as infants transition from sleeping around the clock to a more adult-like sleep/wake cycle. Until further research is completed, Estes said, it is not possible to interpret challenges with sleep as an early sign of increased risk for autism.
The study was funded by the National Institutes of Health, Autism Speaks and the Simons Foundation. Dr. Stephen Dager, professor of radiology at the UW School of Medicine and Tanya St. John, research scientist at the UW Autism Center, were co-authors. Additional co-authors, all at IBIS Network institutions, were Mark Shen, Martin Styner, Sun Hyung Kim and Dr. Joseph Piven at the University of North Carolina at Chapel Hill; Sarah Paterson, now at the James S. McDonnell Foundation; Juhi Pandey at the Children's Hospital of Philadelphia; Jed Elison and Jason Wolff at the University of Minnesota; Meghan Swanson at the University of Texas at Dallas; Kelly Botteron at Washington University in St. Louis; and Dr. Lonnie Zwaigenbaum at the University of Alberta.
https://www.sciencedaily.com/releases/2020/05/200507094747.htm
Put the cellphone away: Fragmented baby care can affect brain development
Maternal infant-rearing link to adolescent depression
Science Daily/January 5, 2016
University of California - Irvine
Mothers, put down your smartphones when caring for your babies! That's the message from researchers, who have found that fragmented and chaotic maternal care can disrupt proper brain development, which can lead to emotional disorders later in life.
While the study was conducted with rodents, its findings imply that when mothers are nurturing their infants, numerous everyday interruptions -- even those as seemingly harmless as phone calls and text messages -- can have a long-lasting impact.
Dr. Tallie Z. Baram and her colleagues at UCI's Conte Center on Brain Programming in Adolescent Vulnerabilities show that consistent rhythms and patterns of maternal care seem to be crucially important for the developing brain, which needs predictable and continuous stimuli to ensure the growth of robust neuron networks. Study results appear today in Translational Psychiatry.
The UCI researchers discovered that erratic maternal care of infants can increase the likelihood of risky behaviors, drug seeking and depression in adolescence and adult life. Because cellphones have become so ubiquitous and users have become so accustomed to frequently checking and utilizing them, the findings of this study are highly relevant to today's mothers and babies ... and tomorrow's adolescents and adults.
"It is known that vulnerability to emotional disorders, such as depression, derives from interactions between our genes and the environment, especially during sensitive developmental periods," said Baram, the Danette "Dee Dee" Shepard Chair in Neurological Studies.
"Our work builds on many studies showing that maternal care is important for future emotional health. Importantly, it shows that it is not how much maternal care that influences adolescent behavior but the avoidance of fragmented and unpredictable care that is crucial. We might wish to turn off the mobile phone when caring for baby and be predictable and consistent."
The UCI team -- which included Hal Stern, the Ted & Janice Smith Family Foundation Dean of Information & Computer Sciences -- studied the emotional outcomes of adolescent rats reared in either calm or chaotic environments and used mathematical approaches to analyze the mothers' nurturing behaviors.
Despite the fact that quantity and typical qualities of maternal care were indistinguishable in the two environments, the patterns and rhythms of care differed drastically, which strongly influenced how the rodent pups developed. Specifically, in one environment, the mothers displayed "chopped up" and unpredictable behaviors.
During adolescence, their offspring exhibited little interest in sweet foods or peer play, two independent measures of the ability to experience pleasure. Known as anhedonia, the inability to feel happy is often a harbinger of later depression. In humans, it may also drive adolescents to seek pleasure from more extreme stimulation, such as risky driving, alcohol or drugs.
Why might disjointed maternal care generate this problem with the pleasure system? Baram said that the brain's dopamine-receptor pleasure circuits are not mature in newborns and infants and that these circuits are stimulated by predictable sequences of events, which seem to be critical for their maturation. If infants are not sufficiently exposed to such reliable patterns, their pleasure systems do not mature properly, provoking anhedonia.
With her UCI team, Baram is currently studying human mothers and their infants. Video analysis of care, sophisticated imaging technology to measure brain development, and psychological and cognitive testing are being employed to more fully understand this issue. The goal is to see whether what was discovered in rodents applies to people. If so, then strategies to limit chopped-up and unpredictable patterns of maternal care might prove helpful in preventing emotional problems in teenagers.
http://www.sciencedaily.com/releases/2016/01/160105132724.htm
Adolescent Stress Linked to Severe Adult Mental Illness
January 17, 2013
Science Daily/Johns Hopkins Medicine
Working with mice, Johns Hopkins researchers have established a link between elevated levels of a stress hormone in adolescence -- a critical time for brain development -- and genetic changes that, in young adulthood, cause severe mental illness in those predisposed to it.
The findings, reported in the journal Science, could have wide-reaching implications in both the prevention and treatment of schizophrenia, severe depression and other mental illnesses.
"We have discovered a mechanism for how environmental factors, such as stress hormones, can affect the brain's physiology and bring about mental illness," says study leader Akira Sawa, M.D., Ph.D., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
"We've shown in mice that stress in adolescence can affect the expression of a gene that codes for a key neurotransmitter related to mental function and psychiatric illness. While many genes are believed to be involved in the development of mental illness, my gut feeling is environmental factors are critically important to the process."
Sawa says the new study points to the need to think about better preventive care in teenagers who have mental illness in their families, including efforts to protect them from social stressors, such as neglect. Meanwhile, by understanding the cascade of events that occurs when cortisol levels are elevated, researchers may be able to develop new compounds to target tough-to-treat psychiatric disorders with fewer side effects than RU486 has.
http://www.sciencedaily.com/releases/2013/01/130117142504.htm
Stress May Delay Brain Development in Early Years
June 6, 2012
Science Daily/University of Wisconsin-Madison
Stress may affect brain development in children, altering growth of a specific piece of the brain and abilities associated with it, according to researchers at the University of Wisconsin-Madison.
"There has been a lot of work in animals linking both acute and chronic stress to changes in a part of the brain called the prefrontal cortex, which is involved in complex cognitive abilities like holding on to important information for quick recall and use," says Jamie Hanson, a UW-Madison psychology graduate student. "We have now found similar associations in humans, and found that more exposure to stress is related to more issues with certain kinds of cognitive processes."
Children who had experienced more intense and lasting stressful events in their lives posted lower scores on tests of what the researchers refer to as spatial working memory. They had more trouble navigating tests of short-term memory such as finding a token in a series of boxes, according to the study, which will be published in the June 6 issue of the Journal of Neuroscience.
Brain scans revealed that the anterior cingulate, a portion of the prefrontal cortex believed to play key roles in spatial working memory, takes up less space in children with greater exposure to very stressful situations.
"We're not trying to argue that stress permanently scars your brain. We don't know if and how it is that stress affects the brain," Hanson says. "We only have a snapshot -- one MRI scan of each subject -- and at this point we don't understand whether this is just a delay in development or a lasting difference. It could be that, because the brains is very plastic, very able to change, that children who have experienced a great deal of stress catch up in these areas."
The researchers determined stress levels through interviews with children ages 9 to 14 and their parents. The research team, which included UW-Madison psychology professors Richard Davidson and Seth Pollak and their labs, collected expansive biographies of stressful events from slight to severe.
"Instead of focusing in on one specific type of stress, we tried to look at a range of stressors," Hanson says. "We wanted to know as much as we could, and then use all this information to later to get an idea of how challenging and chronic and intense each experience was for the child."
Interestingly, there was little correlation between cumulative life stress and age. That is, children who had several more years of life in which to experience stressful episodes were no more likely than their younger peers to have accumulated a length stress resume. Puberty, on the other hand, typically went hand-in-hand with heavier doses of stress.
The researchers, whose work was funded by the National Institutes of Health, also took note of changes in brain tissue known as white matter and gray matter. In the important brain areas that varied in volume with stress, the white and gray matter volumes were lower in tandem.
White matter, Hanson explained, is like the long-distance wiring of the brain. It connects separated parts of the brain so that they can share information. Gray matter "does the math," Hanson says. "It takes care of the processing, using the information that gets shared along the white matter connections."
Gray matter early in development appears to enable flexibility; children can play and excel at many different activities. But as kids age and specialize, gray matter thins. It begins to be "pruned" after puberty, while the amount of white matter grows into adulthood.
"For both gray and white matter, we actually see smaller volumes associated with high stress," Hanson says. "Those kinds of effects across different kinds of tissue, those are the things we would like to study over longer periods of time. Understanding how these areas change can give you a better picture of whether this is just a delay in development or more lasting."
http://www.sciencedaily.com/releases/2012/06/120606164936.htm
Some brain wiring continues to develop well into our 20s
September 23, 2011
http://images.sciencedaily.com/2011/09/110922134617-large.jpg
Science Daily/University of Alberta Faculty of Medicine & Dentistry
The human brain doesn't stop developing at adolescence, but continues well into our 20s, demonstrates recent research. It has been a long-held belief in medical communities that the human brain stopped developing in adolescence. But now there is evidence that this is in fact not the case.
It has been a long-held belief in medical communities that the human brain stopped developing in adolescence. But now there is evidence that this is in fact not the case, thanks to medical research conducted in the Department of Biomedical Engineering by researcher Christian Beaulieu, an Alberta Innovates -- Health Solutions scientist, and by his PhD student at the time, Catherine Lebel. Lebel recently moved to the United States to work at UCLA, where she is a post-doctoral fellow working with an expert in brain-imaging research.
"This is the first long-range study, using a type of imaging that looks at brain wiring, to show that in the white matter there are still structural changes happening during young adulthood," says Lebel. "The white matter is the wiring of the brain; it connects different regions to facilitate cognitive abilities. So the connections are strengthening as we age in young adulthood."
"What's interesting is a lot of psychiatric illness and other disorders emerge during adolescence, so some of the thought might be if certain tracts start to degenerate too soon, it may not be responsible for these disorders, but it may be one of the factors that makes someone more susceptible to developing these disorders," says Beaulieu.
"It's nice to provide insight into what the brain is doing in a healthy control population and then use that as a springboard so others can ask questions about how different clinical disorders like psychiatric disease and neurological disease may be linked to brain structure as the brain progresses with age."
http://www.sciencedaily.com/releases/2011/09/110922134617.htm
Parental absence affects brain development in children
November 30, 2015
Science Daily/Radiological Society of North America
Researchers in China have found that children who have been left without direct parental care for extended periods of time show larger gray matter volumes in the brain, according to a study being presented today at the annual meeting of the Radiological Society of North America (RSNA).
Throughout the world, due to political upheaval, economic necessity or other reasons, parents sometimes are compelled to travel away from home for months or years at a time, leaving their children behind.
In China, large numbers of workers are migrating away from their children in pursuit of better jobs. Researchers wanted to study how this migration has affected the millions of children who have been left in the care of relatives for a period of more than six months without direct parental care from their biological parents.
"We wanted to study the brain structure in these left-behind children," said study author Yuan Xiao, Ph.D. candidate at the Huaxi MR Research Center and the Department of Radiology at West China Hospital of Sichuan University in Chengdu, Sichuan, China. "Previous studies support the hypothesis that parental care can directly affect brain development in offspring. However, most prior work is with rather severe social deprivation, such as orphans. We looked at children who were left behind with relatives when the parents left to seek employment far from home."
For the study, which was led by Professor Su Lui and conducted at the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, MRI exams from 38 left-behind girls and boys (ages 7 to 13) were compared to MRI exams from a control group of 30 girls and boys (ages 7 to 14) living with their parents. The researchers then compared the gray matter volume between the two groups and measured the intelligence quotient (IQ) of each participant to assess cognitive function.
The researchers found larger gray matter volumes in multiple brain regions, especially in emotional brain circuitry, in the left-behind children compared to children living with their parents. The mean value of IQ scores in left-behind children was not significantly different from that of controls, but the gray matter volume in a brain region associated with memory encoding and retrieval was negatively correlated with IQ score.
Since larger gray matter volume may reflect insufficient pruning and maturity of the brain, the negative correlation between the gray matter volume and IQ scores suggests that growing without parental care may delay brain development.
"Our study provides the first empirical evidence showing that the lack of direct parental care alters the trajectory of brain development in left-behind children," Xiao said. "Public health efforts are needed to provide additional intellectual and emotional support to children left behind by parents."
http://www.sciencedaily.com/releases/2015/11/151130084008.htm