Home > Science, Uncategorized > New Findings on Sensory Overload: A First-Person Perspective

New Findings on Sensory Overload: A First-Person Perspective

Guest blog post from Autism Speaks Science Board Member John Elder Robison, author of Look Me in the Eye: My Life with Asperger’s and Be Different: Adventures of a Free-Range Aspergian

According to a press release I received this morning, new research from Cold Spring Harbor Lab might help explain how a gene mutation found in some autistic individuals leads to difficulties in processing auditory cues and paying spatial attention to sound. [Editor’s note: See our related science news story on this Autism Speaks-funded study.]

The study found that when a gene called PTEN is deleted from auditory cortical neurons—the main workhorses of the brain’s sound-processing center—the signals that these neurons receive from local as well as long-distance sources are strengthened beyond normal levels.  That’s the first interesting part of the study.

PTEN has been associated with autism in a number of previous studies. In particular, the PTEN variation has been found in autistic people with larger heads, and it’s suspected as a cause of both additional connectivity in the brain and additional brain cell growth.

How many of today’s autism population have a PTEN variation?  Do you?  No one knows.  It’s one of many genes researchers are studying.

What I do know is that I have abnormal sensitivity to sound, as do many autistic people. Many of us are easily overwhelmed by noises that go unremarked by the rest of the population. For some time, I have realized my excess sensitivity is a two-edged sword. On the one hand, it gave me powerful insight into music and facilitated my earlier career in rock and roll. On the other hand, it has often put me at a disadvantage as I’m rendered inoperative by what others see as ordinary situations.

It’s interesting to read that PTEN may be a cause of that difference. Understanding the genetic foundation of why that happens doesn’t do me much good, but the next part of the study might:

Researchers found that those can be blocked by rapamycin, a drug currently in use as an immunosuppressant. Rapamycin as an autism therapy has been studied before and found beneficial in some cases. This study is one of the first that sheds light on “why” and speaks to a specific mechanism by which we may be disabled.

Now that I’ve come to know many people on the spectrum, I realize I am one of a fortunate few who have significant sensory sensitivity without being disabled by it.  The vast majority of autistic people who write about sensitivity do so in the context of disability. If there were a way to reduce sensory overload, I’m sure a number of folks on the spectrum today would like to hear about it.

One next step might be to see if rapamycin has the same effect in humans, and what other unforeseen effects it may have. Rapamycin has already been tried as a therapy in other contexts relating to autism. A targeted study that looked at the drug’s effect specifically on sensory overload would be very interesting.

It’s possible that this research illustrates a first step on the path to remediating a specific component of disability for many people on the spectrum. Much more testing will be needed to really know if that’s true, but it looks like a promising start.

My biggest concern is that rapamycin may have unforeseen effects elsewhere in the brain, and we won’t be able to understand that until we have conducted a sizeable human trial. We can only do so much by observing and extrapolating from mice.

An interesting aside is that Dr. Zador’s research further supports the emerging idea that excessive brain plasticity is a key component of the brain differences that lead to autism. His research premise is that the PTEN variation causes excess connectivity, and connectivity is a key element of plasticity. I’ve written about that idea in earlier posts.

I read a lot of talk in the autism community that questions why we spend money on genetic research when today’s autistic population needs help now. There is a popular perception that genetic research can only benefit unborn generations, or even worse, be used as a tool for selective abortion.

Dr. Zador’s study shows a clear pathway from a basic genetic study to a possible therapy for autistic people today, if they suffer sensory overload issues. It’s a perfect example of why this kind of work continues to be important and needs to be funded alongside all our other efforts in the autism research arena.

One of the pathways regulated by the PTEN protein involves shutting down an intracellular enzyme called mTORC1, which promotes cell growth, among other things…. While Zador is excited about “this finding that suggests that mTORC1 could be a good therapeutic target for some cases of PTEN-mediated brain disorders,” he is also keen to further pursue his team’s new evidence that cortical hyperconnectivity could be the “final pathway” by which diverse ASD genetic pathways lead to a single ASD phenotype. “Using cortical connectivity as a paradigm for assessing ASD candidate genes could provide insights into the mechanisms of the disorders and perhaps even give us clues to formulate new therapeutic strategies,” he states.

Dr. Zador’s leap from a subtle variation in genetic code to a specific behavioral aberration represents a brilliant leap of intuition and reason, backed up with careful lab work. It’s the kind of result I hope to see when I cast my vote for further genetic studies. This work was originally funded by Autism Speaks and NIH four years ago.

Here’s another really fascinating point to ponder. The PTEN genetic variation has been already associated with certain people with severe autistic disability and people with tubular sclerosis. Now, by associating PTEN with auditory sensitivity, we confront the question:  Do people like me have the PTEN difference too?  No one knows, because that study has never been done.

I’ll just say one more thing in closing. The discovery that PTEN aberrations can lead to sensory overload, and the pathway by which that happens stands separate from any question about rapamycin as a therapy. Don’t let worries about a particular drug blind you to the significance of the first finding.

Other researchers are looking at alternate ways to affect cortical plasticity in general and even connectivity as described in this study.  Rapamycin may end up being a therapeutic answer for some, but it’s equally possible that a better therapy will be developed now that we are beginning to unravel the underlying issues. One day, autistic people who are disabled by auditory overload may be able to “mute” the disability, while retaining enough sensitivity to be exceptional.

That, folks, is what the science is all about.

  1. February 2, 2012 at 11:41 pm

    Awesome article John. I love how you included your perspective because you have Asperger’s. I have triplets who are all on the spectrum. Two of them are very sensitive to the fire drills at school. The school is required to have a fire drill every month. My two kids start having anxiety the beginning of every month till the fire drill is done. In fact my daughter had a terrible time getting to school today even after the school said there was not going to be a drill. Tonight she is telling me she is worried about tomorrow.

    We have noise reduction headphones for them to use at school. I have requested for both of them to be taken out of the building prior to the fire drill but school refuses. It is not only the loud sound but also the blinking lights and the sensory overload. How are you affected by fire alarms? My other son who has Asperger’s had trouble with the fire alarm Kindergarten through 2nd Grade. Somehow he found a way to deal with it.

  2. Janice Miller
    February 3, 2012 at 10:33 am

    An Ear, Nose, and Throat Doctor can help some children with audio sensitivities. A CT scan can show if there are blockages or inflammation that would cause audio sensitivities. After a ENT helped our son eliminate infection, inflammation, and irritation from bacteria, he no longer avoids noisy situations like pep rallys and basketball games. It made a world of difference and opened the doors for enjoyment instead or retreat. While we wait for genetic mutation answers, a trip to the ENT may be worthwhile, especially if there is a history of ear infections, strep throat, or reflux from GI issues.

    • Jennifer
      February 3, 2012 at 1:37 pm

      Janice- my ASD kiddo has sound sensitivities too and we took him to a pediatric GI specialist at Children’s who found nothing (and we KNOW he has GI issues as he has runny poops every single day since he turned 2..he is almost 3). I’d like to try the ENT route! What do I ask them to test for???

  3. Mita
    February 3, 2012 at 1:15 pm

    Auditory Hyper-sensitivity is often due to the stirrup muscle in the middle ear not doing its job properly and not protecting the ears enough. The Alfred Tomatis Method can really help to get the stirrup muscle going again, and working in tandem with the hammer muscle, in order to protect the ear. These tiny muscles can be trained…. life becomes a lot more bearable when they are limber……

  4. Suzanne B.
    February 3, 2012 at 2:07 pm

    When my 8yo son walked into my home office yesterday wearing his DeWalt ear muffs, I knew he was heading to either the pencil sharpener or the hand vacuum! He also has a pair at school for environments/situations that are too loud/distracting. I’m grateful that he is old enough and self-aware enough now to recognize when his aural sensitivity is going to be a challenge and prepare for it. We can even go to regular movies (instead of sensory friendly only) when he is in the right frame of mind for it. In those cases, we take ear buds with us to muffle the sound, though they often remain in my purse as backup. But the rule in our family is if it gets to be too much, too overwhelming, we will leave the environment without regret, shame or moaning about the money we just “wasted.”

  5. February 3, 2012 at 3:45 pm

    THANKS, John! When I was little I had hyper sensitivity to sounds (for instance, I would hear a high pitched hum when the TV was on in the house, even with the volume off) that others couldn’t hear. Though I don’t have autism, the workings of the brain and how people’s perceptions are different has always fascinated me. I appreciate your delving into this very important topic. Keep up the good work. You are inspiring me to study more about it! I wrote an article on EMPATHY – and mirroring in the brain you might enjoy, here: http://www.edudesigns.org/EmpathyRules.html

  6. James
    February 3, 2012 at 5:34 pm

    So glad that I don’t have hypersensetivity to sound, like my brother, (who, unlike myself, is not autistic). On the other hand, like Mr. Elder Robinson related, hypersensetivity is not exactly a disability. I’m one of those guys who live by the creed that ‘every problem is an opportunity in disguise’, and I have found that applying this to my Asperger’s Syndrome has really helped in life. Ever since I heard the phrase in 5th grade, I’ve been able to go around life (relatively) normally.

  7. Norma Duhon
    February 3, 2012 at 8:59 pm

    My daughter, now 27 yrs. old, had hypersensitivity to loud noises AND certain visuals (masks, costumes, etc). It became evident around 2 years of age; July 4th fireworks, Halloween masks (even in stores), Chuck-E-Cheese, pep rallies with school mascot (Cardinal) were meltdown situations that we chose to avoid as much as possible. I was a teacher in my daughter’s school, and her first grade teacher insisted she attend in-school pep rallies until the administration backed me up, witnessing my daughter’s intense reaction. At Christmas time, the same teacher allowed a high school student to hide behind a couch in her classroom, wearing a hairy wolf mask and jumping out growling to “surprise” the children. At this point, her pediatrician recommended therapy. The parental interview questions were very thorough and personal, and obvious that molestation was being considered a cause for her sensitivities. It was a few years later I saw an article about over-sensitive Central Nervous Systems in some children that I felt my “aha!” moment.

    I now have a grandson with Asperger’s Syndrome. I hope and pray answers and help come for our children’s children.

  8. ML
    February 4, 2012 at 8:08 am

    PTEN is involved as an enzyme with ROS, Cu/Zn SOD,the regulation of ZnT1 (zinc transporter 1), another target gene of MTF-1, Depletion of PTEN reduced MT (metallothionein) gene expression and increased cellular sensitivity to cadmium toxicity, and counteracts the funcion of PI3K (that phosphorylates inositol)… however, the only role that is cited is the tumor suppression.
    As a lateral note,the problems with Zn/Cu/SOD, the oxidative stress, the MTF1, etc in ASD are widely published- ….but are not cited in this press report…besides the results are in mice- and no oxidative stress, Cu/Zn, MTF-1 were considered because system biology was not considered.
    I wonder when system biology at the level of XXI centuryknowledge is going to be considered in this kind of studies- It is not the presence or not of proper transcription of certain genes, It is also how transcripted proteins interact in vivo….
    My son had auditory hypersensitivy, that was incredibly reduced when inflammation, oxidative stress, methylation abnormal status, gluten intolerance, nutritional, metabolic, mitochondrial and biochemical issues were considered. what I want to point out is that- beyond one role, in vivo in human beingsthe gene involved with the particular enzyme has multiple roles and therefore other dysregulations could be related to the auditory hypersensitivity.
    Mr Robinson, thank you for your perspective.

  9. ML
    February 4, 2012 at 8:12 am

    Citations
    Cancer Invest. 2011 May;29(4):253-6. The protective effect of Cu/Zn-SOD against oxidative stress after PTEN deletion.Yu C, Wang P, Li S, Wang X, Yu Z, Wang Z.

    …”These results suggest that negative regulation occurs through interactions among ROS, Cu/Zn-SOD, and PTEN, and such a disequilibrium between oxidation and antioxidation could contribute to the reduced antioxidative capacity in PTEN null cells. These studies will guide further investigations into the biological function of PTEN.”

    Biochem J. 2012 Jan 1;441(1):367-77.
    PTEN interacts with metal-responsive transcription factor 1 and stimulates its transcriptional activity.
    Lin MC, Liu YC, Tam MF, Lu YJ, Hsieh YT, Lin LY.

    “Analysis of enzymatically inactive PTEN mutants demonstrated that protein but not lipid phosphatase activity of PTEN was involved in the regulation of MTF-1 activity. The same regulatory role of PTEN was also noted in the regulation of ZnT1 (zinc transporter 1), another target gene of MTF-1.”

    Cell Signal. 2012 Jan 20. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling.Ray PD, Huang BW, Tsuji Y.
    “This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases, PI3 kinase, PTEN, and protein tyrosine phosphatase), ROS homeostasis and antioxidant gene regulation (thioredoxin, peroxiredoxin, Ref-1, Nrf-2), mitochondrial oxidative stress, apoptosis, and aging (p66Shc), iron homeostasis through iron-sulfur cluster proteins (IRE-IRP), and ATM-regulated DNA damage response.”
    and these are a few

  10. ML
    February 4, 2012 at 3:22 pm

    I do think that this kind of recent research is much more important

    http://www.nimh.nih.gov/science-news/2012/gene-regulator-in-brains-executive-hub-tracked-across-lifespan-nih-study.shtml

    “This new study reminds us that genetic sequence is only part of the story of development. Epigenetics links nurture and nature, showing us when and where the environment can influence how the genetic sequence is read,” said NIMH director Thomas R. Insel, M.D.”

    ·In most cases, when chemicals called methyl groups attach to regulatory regions of genes, they silence them. Usually, the more methylation, the less gene expression. Lipska’s team found that the overall level of PFC methylation is low prenatally when gene expression is highest and then switches direction at birth, increasing as gene expression plummets in early childhood. It then levels off as we grow older”

  11. Katie Wright
    February 6, 2012 at 11:28 pm

    Finding a good occupational therapist for your child is 1,000x better than trying a dangerous drug!
    This study is crazy.
    I have a super sensory kid and so much was accomplished w/ lots of basic research (me and my computer and ARI and NAA conferences) a good sensory diet. Let’s research sensory integration therapy!

    Also for Pete’s sake clean up the diet, it is cheap, no side effects and can only help. Get rid of the garbage and anything w/ food dyes. It helped my son’s hyperactivity so much.

    • February 8, 2012 at 1:02 am

      I agree 100%! Bravo Katie! Though my kids were not in the syndrome, they were hyperactive after eating anything with artificial food colorings, or too much sugar! I limited them to one piece of candy a week, and they’d work like crazy for it. I illustrated charts for each of them with positive behaviors to work on. If they accomplished their ‘good behaviors’ or ‘jobs’, they’d get their treat at the end of the week. They are all grown now, so, I put my free behavior charts on the web, here: http://www.gomommygo.com/thankdontspank.html for other mom’s to download and print up along with other great tips I’ve collected along the way.

  12. ML
    February 7, 2012 at 7:44 pm

    Hi Katie
    I agree with you,

    http://www.medscape.com/viewarticle/524753_6

    I would say sensory integration therapy plus proper treatment of CMP (concomitant medical problems) to ASD diagnosis-in my son´s case.
    The poiunt of hypersensitivity is so much associated to diet, nutritional defficiencies, ototoxicity of certain drugs,xenobiotics and fungal infections and connections to the amygdala

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