CHD8 Gene and Autism

Dozens of genes have been found to be correlated with autism. However, according to James P. Noonan, an associate professor of genetics, ecology and evolutionary biology at the Kavli Institute for Neuroscience at Yale University, one of these genes, CHD8, has been found to be a “master regulator in the developing human brain” and to “control the expression of many other genes.” The function of CHD8 is thought to be to regulate gene expression by “modifying the way DNA interacts with histones, proteins present in the nucleus of every cell that wind long strands of DNA.” People who have “a loss-of-function mutation in this gene, which inactivates the corresponding protein, are very likely to have an autism diagnosis.” Noonan’s study was published in March in the journal Nature Communications.

In the study, Noonan and his fellow researchers looked at developing brains of people and mice as well as neuronal stem cells. They found that CHD8 bound to thousands of sites in the brains of the humans and mice as well as the stem cells. Next, they reviewed previous genetic studies and found that “autism-associated genes were more likely to be targeted by CHD8 than expected by chance.” Finally, they looked at whether CHD8 had a regulatory effect on these genes associated with autism. The researchers looked to accomplish this goal by “reducing the expression of the CHD8 gene in cultured human neuronal stem cells and explored what, if any, gene expression levels changed.” The result of this reduced gene expression was the impaired regulation of many of the targeted genes but “autism risk genes were most strongly affected.” Mr. Noonan believes that as a result of this type of research, answers to what “biological pathways and developmental processes that are affected in autism” will be developed.

Source: News.Yale.edu March 10, 2015

Brain Anatomy Differences in Autism

The Medical Research Council UK Autism Imaging Multicentre Study which was comprised of the Institute of Psychiatry at Kings College in London, the Autism Research Centre at the University of Cambridge and the Autism Research Group at the University of Oxford analyzed the brains of males with autism versus male controls using quantitative magnetic resonance imaging. The study was comprised of 89 men with autism spectrum disorder (mean age 26 and “full-scale IQ 110”) and 89 “male control participants” (mean age 28 and “full-scale IQ 113”). The differences in the two groups were identified statistically through “partial least squares analysis.”

The results of the study showed significant brain anatomy differences between the two groups although the adults with autism spectrum disorder did not “differ significantly from the controls in overall brain volume.” Study individuals with autism did have “significantly increased gray matter volume in the anterior temporal and dorsolateral prefrontal regions and significant reductions in the occipital and medial parietal regions as compared with controls.” The importance of these regional differences in neuroanatomy is that there was a “significant correlation between these differences and the severity of specific autistic symptoms.” Additional differences between those with autism spectrum disorder and the male controls were that those with autism had “spatially distributed reductions in white matter volume.”

In summary, quantitative MRI showed that although the overall brain volume of those with autism spectrum disorder and the controls (commonly referred to as the neurotypical) is not significantly different, there are significant brain anatomy differences in gray matter volume as well as white matter volume in those with autism spectrum disorder compared to the neurotypical; and further, the regional differences correlated with autistic symptom severity.

Source: Journal of the Archives of General Psychiatry; Jan. 2, 2012; copyrighted by the American Medical Association as detailed on the Nuffield Department of Clinical Neurosciences Medical Sciences Division of University of Oxford website: http://www.ndcn.ox.ac.uk/publications/343223.

Autism and Mealtime

So I have been reading a lot of blog posts about neurotypical parents and their struggles with their autistic child or children at mealtime. If your family has an enjoyable mealtime where everyone is ready to join hands and sing Kumbaya, then this article is not for you. On the other hand, if mealtime at your house is more like hell on earth, and you go to bed at night craving Valium, then read on.

Psychologists and all sorts of pro-family professionals like to extol the virtues of family mealtime. It’s the part of the day when everyone in the family gets together to compare notes and agendas about the day, and check-in as it were. Additionally, as if contending with society’s norms wasn’t enough, you probably have relatives and friends who are quick to remind you of the importance of “3 squares a day,” “eating everything on your plate because there are starving Africans,” “mealtime is synonymous with family time” etc. etc. ad nauseam.

But, how about we look at mealtime from the perspective of an autistic person. I have been on the autism spectrum for over fifty years and I raised a daughter on the autism spectrum so I would like to share some observations. I don’t purport to know what it is like for every autistic person, but I can give some perspective to the neurotypical out there. As the vast majority of autistic children have some type of sensory issue, let’s look at what mealtime may be like from the viewpoint of one with sensory issues.

  • Light:  Is it bright in your kitchen or dining room at mealtime? Most people don’t eat in the dark unless the power is out, so chances are there is a fair amount of light emanating from light bulbs at dinner as well as sunlight during the day.  Does your child act up when in the presence of fluorescent light, bright sunlight or just a well-lit room?
  • Noise: Is it quiet like a library at your breakfast or dinner table? Or is there a lot of talking, bustling about, moving of chairs etc.?
  • People: Does your child get antsy/agitated when around more than 1 person at a time? Does your child prefer a lot of alone time? How does/he she react with a group of people around a table?
  • Textures/Taste: Does your child only like certain textures of food?  Certain colors of food?  If there is more than one item on the plate, does he get agitated if the food touches or starts running together? Does unfamiliar food send your child into a meltdown?
  • Smell: Does your child have a heightened sense of smell? Do certain smells agitate him? How about a variety of smells all at once?

Is it any wonder your child does not do well at mealtime or refuses to eat?

When I raised my daughter, she and I were the only ones in the home and as I mentioned, we both are on the autism spectrum. The family meal concept (breakfast, lunch, dinner) went out the window early. You probably noticed your autistic child only likes a few foods (little sarcasm there). We on the autism spectrum will eat the same foods most of the time, if you let us, until we either get tired of the food (which can take a VERY long time) or we have something else put in front of us that looks more interesting. I have eaten peanut butter sandwiches for lunch (or sometimes for dinner) pretty much every day for the last fifty years. Really. My daughter and I when she was growing up, rarely liked the same foods at the same time or wanted to eat at the same time of the day. I could have forced us to have mealtime, but it seemed counterproductive. Yes, we did eat a meal together on occasion outside of the home at a restaurant or at a relative or friend’s house. I do advocate having a “group meal” once in a while to teach your child about the neurotypical world, but forcing your autistic child into 2 or 3 family meals around a table per day is going to put you into an early grave. By the way, my daughter and I are healthy adults (from a nutritional standpoint—anxiety issues are another story).

Do yourself and your nervous system, not to mention the poor overloaded nervous system of your child on the autism spectrum, a favor, and try to give your child small amounts of no more than 1 or 2 foods at a time. Combine that with an eating environment that is one to one and surrounded by low light, low sound and low disruption. Inotherwords, have eating take place in an environment as soothing as possible. Experiment and see what different foods your child may like. Above all, don’t give up. Just because your child does not like the food now, doesn’t mean he won’t want to try it 3 months from now or a year from now.

Do NOT battle with your child over eating. Battling over food turns eating into an anxiety-producing activity which can lead to life-long eating problems and even eating disorders. Introduce new foods slowly and don’t expect miracles overnight. Eventually, try giving foods from different food groups at intervals during the entire waking day to maintain nutrition. Resist the temptation to believe “my child only likes …” and repeatedly just give him that food. You are not doing him any favors.

Brain Inflammation a Key Finding in Autism

A collaborative study between Johns Hopkins School of Medicine and the University of Alabama concerning an analysis of autopsied autism and control brains was published in the December 2014 journal Nature Communications. The study found that although there are many different combinations of genetic traits that can cause autism, brains that are affected by autism show “genes responsible for inflammation responses seemed to be perpetually turned on.”1

The study involved 104 brain samples from 72 individuals where the researchers analyzed gene expression. They found that a “specific type of support cell known as a microglial cell” appeared to be “perpetually activated in the autism brains.” According to Dan Arking, Ph.D., an associate professor in the McKusick-Nathans Institute for Genetic Medicine at the Johns Hopkins School of Medicine, “inflammation is unlikely to be [autism’s] root cause…rather a downstream consequence of upstream gene mutation…” and that the “next step would be to find out whether treating the inflammation could ameliorate symptoms of autism.” Another researcher involved in the study, Andrew West, Ph.D., an associate professor of neurology at the University of Alabama, noted further that “this type of inflammation is not well understood, but it highlights the lack of current understanding about how innate immunity controls neural circuits.”1

So what is this microglia?

Microglial cells are the primary immune cells of the central nervous system. They respond to pathogens or injury by becoming “activated” where they change form and structure, increase greatly in number and migrate to the site of the injury or pathogen. At the site, they phagocytose and remove pathogens or damaged cells. Their secretions increase and direct the immune response. Though microglia often have a “protective role, they also have been studied for their harmful roles in neurodegenerative diseases and brain injuries, such as Alzheimer’s disease, Parkinson’s disease, ischemic injury, and traumatic brain injuries.”2

 

Sources: 1 Hopkinsmedicine.org/news/media/releases/

2 Faculty.sites.uci.edu/kimgreen/bio/microglia-in-the-healthy-brain/