Guest Post: The Twinkle Light Model of Autism and the Brain

By Nathalia Holt

Little wisps of blonde hair peek through before Eleanor’s head pops up from behind the chair. She gives me a big smile, a wave, and then runs off, yelling ‘bye-bye’ at the top of her little lungs. Eleanor is our first child, she’s twenty-months-old, constantly oscillating between feisty and willful, silly and sweet. At this age it’s almost as if you can see the neurons connecting in her brain, each new experience bringing the world closer to her tiny baby fingers. As a scientist and nervous first time mom, I know that twenty months is not only a critical age in development but also the best time to catch the early symptoms of autism spectrum disorder.

A decade ago, diagnosing a child younger than three with autism was unheard of. In the years since, several studies have shown us that when autism is caught sooner, before two years old, and is accompanied by early therapy, the outcome is better. Children receiving early therapy not only have significantly higher IQs, but their everyday skills, like brushing teeth and having dinner with their family, are improved. These findings have led to a push in early intervention. After a study published in the Journal of Pediatrics last year, many pediatricians use an autism questionnaire at the twelve-month check-up. The idea being, the sooner the disease is spotted, the sooner it can be treated, and the better the ultimate outcome.

This year the CDC reported a shocking increased prevalence in autism. The number of children being diagnosed is up 78% since 2002. This statistic has sparked fiery debate. Once centered on the debunked role of vaccines, today we have new questions to argue about. Is increased prevalence the result of increased awareness? Better screening? An unknown environmental contributor? Does a genetic basis exist?

There are a few things we do know about the cause of autism. Autism tends to run in families. Supported by the Autism Genome Project, hundreds of patients have had their genomes screened. The findings have been remarkable; certain mutated genes are highly associated with the disease, seemingly passed down across generations. These genes encode synaptic proteins, proteins that bridge neurons and are critical to the collective electrical signaling of the nervous system. Think of these networks like a strand of twinkle lights. When the wires connecting the bulbs together begin to fray, the entire strand stops working properly, blinking in and out. Intriguingly, these genes are implicated in other neurodegenerative diseases such as Alzheimer’s and Parkinson’s. However, this research has been seriously hampered by the lack of an animal model for autism. After all, what kinds of experiments are safe to do in children?

Researchers at several universities have addressed this by knocking out the function of these genes in mice. They then painstakingly followed their behavior, tracking their social interaction and communication. They found that mice with the mutated version of these genes displayed hyperactivity, repetitive grooming and abnormal vocal and social behavior, in essence, the classic symptoms of autism. For the first time, a clear physiological mechanism for autism has been uncovered.

Building on this, research published in Nature this past June, shows that there may be a way to improve the social behavior of these genetically impaired mice. By stimulating the proteins lost in autism-associated genes, researchers were able to rescue the function of a signaling molecule on the surface of neurons that is critical to memory and learning. This treatment lifted the telltale signs of autism, resulting in mice with normal social interaction.

This month, new research, pursuing innovative, early therapies for autism was published in Nature. Researchers treated a mouse model of Dravet’s syndrome, characterized by impaired learning and autism spectrum behavior, with a drug called clonazepam. Treatment with this drug completely rescued the social behavior of the mice by repairing communication between genetically impaired neurons. This exciting work is the latest chapter in a new trend in studies that highlight the genetic foundation behind some autism disorders as well as the potential for new childhood therapies.

Autism is complex; this type of treatment may or may not result in a viable future therapy. Yet this work has the potential to usher in a new wave of autism therapy, one in which we are able to map genetics to brain function, where children receive personalized therapy specific to their genetic make-up. We’re not there yet, but as I fret over my toddler’s building social skills, I’m hopeful about the future of autism.

Nathalia Holt, Ph.D. is an HIV fellow at the Ragon Institute of MGH, MIT and Harvard University. Nathalia is interested in how the individual experiences of patients and physicians influence medical research. She is currently writing on her first book, THE TWO BERLIN PATIENTS, exploring the personal stories behind two of the most influential HIV cases and the future of the epidemic, to be published by Dutton/Penguin. Nathalia lives in Boston, MA with her husband and baby daughter. Follow her blog and on twitter @nathaliaholt.

Transition Time

Oh my goodness, things have gotten hectic. I know I have neglected the blog, but I’m gearing up for teaching next week and I’m suddenly juggling more a few more responsibilities than I’m used to. Once I figure out how to keep all these balls in the air, I hope I can carve out more writing time again.

It has been a big week for our family. It was Cee’s first week of part-time day care. She seemed to cope with it beautifully. Not surprisingly, I have struggled with it more.

Picking out her new backpack

In the week before she started there, we had three play dates at Cee’s day care, a small in-home program. Cee jumped right into circle time, outdoor play, and meals with the other kids while I watched quietly, usually from a distance. She only clung to me for a few minutes on the first day, and then she was off. She wanted to play with the toys and be a part of the group, and she seemed confident with them. I could tell she was really ready for this change.

After we left our last play date, I told Cee that next time we came, she would stay to play with her new friends and her caregiver – we’ll call her Annie – would take care of her while I went to work. She gave me a funny look.

Over the next few days, I reminded Cee of this plan several times. We would remember something she did at day care or one of her friends there. Each time it came up, I would say something like, “Next time you go to Annie’s house, you will stay to play with the other kids while Mama goes to work.”

Cee: “Yeah.” Then usually a pause, and then, “Mama?”

Me: “Mama will go to work for a little while, but then I’ll come pick you up at lunchtime.”

Cee, nodding her head: “Yeah.” (This leaves me wondering – what exactly does a kid like Cee think of when she imagines “work?”)

On the night before her first day, we packed her bag with diapers and a few changes of clothes, and we repeated the same conversation. Except this time, I could tell that she knew exactly how it would go. She just needed to hear it one more time. She seemed to understand the plan, and she seemed ready. Continue reading

The Last Word on Sleep Training?

In a study published in the journal Pediatrics this week [1], an Australian research group found no evidence of harm in kids that were sleep-trained, 5 years after the fact. This is the longest follow-up study of sleep training to ever be published, and it’s a randomized controlled trial no less.

Not surprisingly, the media has jumped all over this study with headlines like this one from the Huffington Post: “Baby Sleep Training Methods Safe For Infants.” (The best part about that article is that, below it, there is a link to another HuffPo article from last December entitled, “Cry It Out: The Method That Kills Baby Brain Cells.” That’s a great demonstration of how much the media loves this story and why parents are probably sick of hearing judgment on it either way.)

Parents – particularly those of us who sleep-trained our kids and enjoyed the benefits – are breathing a sigh of relief. I’m happy if the coverage of this study allows parents to shed an unwarranted layer of stress and guilt. If you’ve been following my blog for a while, then you know how I feel about sleep training. After reviewing the literature on this topic, I have concluded that there is no evidence that sleep training harms kids. In contrast, there is a significant body of literature that sleep deprivation poses very real risks to families and that sleep training is often helpful in these situations. It may not work for all babies and parents, but when it does, it can make all the difference.

So where does this new study fit in with the previous research in the field?

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A New Baby

No, not mine. But I got your attention, didn’t I?

Our closest friends have a newborn, and his arrival has changed all of us. We don’t have any local blood relatives – all of BabyC’s grandparents and aunts and uncles live at least a plane ride away. But these friends are family. They live just a few blocks from us, and we are the kind of friends who drop in on each other without calling (or texting) first. This baby – we’ll call him Little Sprout – is their first child.

BabyC and I visited Little Sprout at the hospital on the first afternoon of his life.

I watched BabyC closely as she met Little Sprout for the first time, curious to see how she would welcome this new member of the family. BabyC is very close to Little Sprout’s mom and dad, and I wondered how she would feel about being second fiddle to a new baby.

Little Sprout, being a newborn, cried within a few minutes of our first meeting. BabyC looked immediately concerned, demonstrating that the innate human response to an infant’s cry is to do something, right away. BabyC turned to face me, started mimicking Sprout’s cry, and emphatically signed “milk” to me as if to say, “Mama, do what you do and help this baby!”

I thought, “Well, I’ve done this before. Sure thing, let me hold the little guy.” I picked up Little Sprout and tried my best to soothe him (but no, not offering milk), but he continued to wail. BabyC echoed his wail and continued to look worried. I handed Little Sprout over to his mom, and BabyC watched as she began to breastfeed him.

I observed as BabyC processed what this meant. Her dear friends had become parents, and it was their job to care for Little Sprout. After this first day, when Sprout cried, BabyC pointed at his mom and signed milk to her.

Over the last month, we’ve seen Little Sprout nearly every day. BabyC has quickly learned the basics of newborn care: milk, poop, sleep, and cry. At home, she asks about Sprout often.

“Baby?”

“Baby Sprout is home with his mom and dad.”

“Boop?”

“Yes, Sprout does poop a lot. All babies poop a lot, and we have to change their diapers often.”

“Hmmm.”

The arrival of Baby Sprout also inspired us to pick up BabyC’s first realistic-looking baby doll. Baby Doll came with a stroller, and BabyC pushes her all around the house. She really loads up the stroller, hanging bags and hats from the handle, and piling the stroller with blankets on top of Baby Doll. (She’s a new mom, and she still thinks that she has to load up the entire nursery when she goes out. Cut her some slack.)

She also changes Baby Doll’s diaper quite often, because as we all know, babies boop a lot. And sometimes Baby Doll’s diaper changes require a LOT of wipes, like a pile of them on the floor to get the job done. Sigh.

Best of all, in my mind, BabyC has taken on the responsibility of feeding Baby Doll. When we picked her out in the store, BabyC couldn’t wait to hold her. I pulled her out of the box so that she could play with her while I finished my shopping. Waiting in line to check out, Baby Doll started crying (typical baby behavior, right?), and BabyC pulled up her shirt and started nursing on the spot. I’m so glad that Target has become more comfortable with nursing in public, because BabyC was not showing much modesty. (Actually, nobody ever bats an eye about breastfeeding in public here in Eugene, doll or not.) I have also walked into BabyC’s bedroom to find her sitting in our rocking chair, where we usually breastfeed, nursing her Baby Doll while reading a book. Sometimes, Baby Doll needs to eat in the hallway, too. This is true feeding on demand, folks.

I have been impressed with BabyC’s level of care for Little Sprout. She is clearly empathetic when he is in distress, and she’s practicing the basics of newborn care. Seeing BabyC with Little Sprout has made it obvious that she really is not a baby anymore. She’s a toddler – and an independent, outspoken, and caring one at that. I can’t go on calling her BabyC forever. Her new blog alias will simply be “Cee.”

Sprout’s arrival and BabyC’s response to him has made us think more about trying to have another baby soon. It still overwhelms me to think of caring for a newborn and a toddler, but now I can actually imagine how we might make room within our family for a new little one.

When we were pregnant with BabyC, Husband and I started thinking about an “ideal” child spacing. We both agreed that we wanted two kids (Me: “Well, at least two.” Husband: “Two.”). Husband thought we should space them as closely together as possible, so that they would grow up being close friends. I wanted them a bit more spaced out. I wanted time to really let BabyC be a baby, to enjoy being with her and giving her my full attention for a few years. I wanted our second child to have enough distance so as not to grow up in BabyC’s direct shadow but not so much distance that they couldn’t relate to each other. I’ve said for a while that I think three years is a good inter-child spacing, and Husband has basically deferred to me on this decision. But now, I’m feeling antsy. I also know that it may take me some time to get pregnant, because it did the first time around. We can only plan so much, and then we have to leave the rest to a little physiological roll of the dice.

If you have more than one, how far apart in age are your children? Do you think there is an ideal spacing?