Stories from IMFAR 2014: A Refreshing Refocusing

CaptureIn addition to learning about autism awareness in Singapore, I got a lot out of the International Meeting for Autism Research, held a few weeks ago in Atlanta. I wrote a post for the Autism Science Foundation blog in which I share some of the major themes discussed at the meeting. Head on over to the ASF blog if you want to check it out!

Link: http://autismsciencefoundation.wordpress.com/2014/05/29/imfar-2014-a-refreshing-refocusing/

When Silver Bullets Hurt

The apparent increase in autism prevalence over the past decade has driven this disorder into the focus of our nation. This attention has led to a race for the cure, so to speak, a desperate search for a silver bullet to unlock the secrets of autism and cure its wide-ranging symptoms.

But this race is futile. Autism is extremely complex with both genetic and environmental factors, and no single treatment is likely to benefit everyone with autism or improve more than a few of its many symptoms. Searching for a silver bullet is not only pointless but also dangerous, as some of the proposed cure-alls may actually hurt more than they help.

The Food and Drug Administration recently released a consumer update warning families against false claims of cures for autism. Some of the treatments under question include removing important metals from the body in a process known as chelation and an ingestible “miracle mineral solution,” which turned out to be bleach. In the report, the FDA warns that these treatments are not only largely ineffective but could also lead to “serious and life-threatening outcomes.”

When the treatments above have proven fruitless, doctor-salesmen in Panama and other foreign countries have offered up therapies usually reserved for cancer treatment, such as stem cell and bone marrow transplants. These highly invasive, unregulated treatments are only informed by the preliminary results of exploratory animal studies published over the last few years. Although a clinical trial for stem cell therapy in autism is underway, a reminder is needed: autism is not cancer, and it will not be treated effectively if viewed as such.

Even an FDA-approved medication for aggression and irritability in autism, risperidone, has come into question for serious side effects. According to recent studies, this antipsychotic drug may cause metabolic dysfunction and significant weight gain, while only providing behavioral benefits for some individuals. A recent study exploring the combined results of many other studies led to the conclusion that risperidone and a similar drug, aripiprazole, have “substantial adverse effects and that each compound has a specific secondary effect profile that should be taken into account in treatment decision-making.”

The available treatments for autism, whether quack or FDA-approved, have a skewed cost-benefit ratio, in which the risk of harmful side effects outweighs the chance of true benefits. Scientists need to take treatment research back to the core symptoms of autism, especially social communication deficits. The utility of combo-therapies, in which medication and behavioral therapy are given together, should be further explored.

Treatments should stem not from a trial and error approach, but from a bottom-up approach, in which core symptoms and their potential underlying mechanisms inspire treatment ideas. Ultimately scientists and physicians need to focus solely on research-driven, patient-centered treatments. Any supposed silver bullet is really just a shot in the dark.

Stories from IMFAR 2014: Autism (Un)awareness in Singapore

Photo source: Flickr

Photo source: Flickr

In Singapore, a highly developed, first-world country, autism awareness and educational support may be sorely lacking.

Over lunch today at the International Meeting for Autism Research in Atlanta, I sat next to Lela Iuorno from Singapore. Her eight-year-old son, Luca, has autism. Iuorno is at IMFAR hoping to learn more about available pharmacological and behavioral interventions for her son. She is particularly invested in autism research, as she is not only Luca’s parent but also his behavioral aide in school.

Behavioral aides, referred to as “shadow support” in Singapore, are not typically available in the school systems in Singapore. In fact, Iuorno has spent a lot of time trying to convince public schools in Singapore to provide access to behavioral aides in the classroom.

“It’s a lot of fighting,” she said. When Luca had attended three different schools before he finished preschool, Iuorno decided to take the reigns herself. She now attends school alongside Luca 5 days a week, providing the assistance he needs to stay focused during his classes. She works nights and weekends to offset the lost income she would have if she wasn’t serving as Luca’s aide. She’s constantly working to do what’s best for her son, she said.

“I feel like a one woman army,” she said.

Another obstacle Iuorno has encountered in Singapore is a lack of understanding amongst teachers and students about what autism actually is. There is a common misconception that autism is a temporary condition. Teachers have told Iuorno that when Luca “gets better” his experience at school will improve.

Additionally, students like Luca who have autism but do not display obvious behavioral symptoms, such as outbursts, are assumed to be fine. Thus, their individual barriers to learning are largely ignored.

“These children can’t survive [in public schools],” she said. Yet, there are few private special education schools in Singapore, and, of the ones that exist, getting in is difficult.

Despite its developed status, Singapore lacks well-organized special education systems for autism, in which trained behavioral aides are available. But, more importantly, Iuorno believes Singapore is in need of accurate awareness about autism and its heterogeneous symptoms. This unawareness is hurting the education of children like Luca.

“It’s true and it’s sad,” Iuorno said.

A Breath of Not-So-Fresh Air

A paper published last week in Environmental Health Perspectives had the autism community all atwitter last week, quite literally. It was clear something was up when my Twitter feed suddenly filled up with tweets about a national study, led by Andrea Roberts and colleagues at Harvard University, “confirming the link between autism and air pollution.”

Utilizing Environmental Protection Agency records of hazardous air pollutant concentrations, the researchers examined levels of air pollution in the year and location in which women lived when they gave birth to their children. These mothers were enrolled in the Nurses Health Study II, a large sample of female nurses that has been followed since 1989. To focus their investigation, the researchers studied air pollutants previously found to be associated with autism, such as metals and diesel particulate matter. Overall, they found positive associations between perinatal exposure to several air pollutants and autism, meaning the greater the concentration of these pollutants, the greater chance of a child having autism. They also showed that some of these associations were stronger for boys than for girls.

However, this highly publicized study on air pollution is not exactly a breath of fresh air. Several things reveal weaknesses in the design and interpretation of this study:

1. On Twitter, Forbes writer Emily Willingham, made an interesting point:

Screen Shot 2013-06-26 at 8.20.42 PMAir pollution may be related to autism, just as countless environmental factors are, but it clearly isn’t a major player in its etiology, or causation (as much as I hate to use that word). For more of Emily’s thoughts on the autism/air pollution relationship, see this insightful post about a previous study.

2. While the Nurses Health Study provided a large sample, there is a significant confound with only studying children born to nurses. In an Autism Research paper, Gayle Windham and colleagues demonstrate a relationship between maternal occupational exposure to chemicals, as well as other potential toxins, and autism. Particularly, maternal exposure to disinfectants, as can be seen in nurses and other medical professionals, seemed to be related to autism.  While this finding doesn’t negate the air pollution finding, it certainly complicates the picture.

3. The children in the autism group in this study were noted as having autism, Asperger’s and PDD-NOS, or, as was explained more vaguely, “may have been on the autism spectrum.” Including multiple subtypes of autism in a study sample is common, but, again, it provides another confound, especially considering the subtype-specific findings related to smoking during pregnancy, which I discuss in this post.

4. Regarding the researchers’ interpretation of these findings, there was much to be desired. Yes, an association between air pollutants and autism was demonstrated. But why or how? In other words, what potential genetic or developmental underlying mechanisms are set into motion by air pollution exposure? For now this is just a correlational, not causational, finding. Simply stating the supposed existence of an association doesn’t provide many answers.

While an interesting concept, the autism and air pollution “link” needs further exploration, and, hopefully, a more reserved reception as future studies are published.

Risk factors in autism: A deeper look at the subtype argument

It has been well demonstrated that prenatal (during gestation) and perinatal (after birth) risk factors are associated with autism spectrum disorders. But which risk factors have a significant relationship with the prevalence of autism remains up for debate. Several papers argue that maternal stress during pregnancy is an important risk factor for autism, but even this proposition is muddled, as several prenatal stressors do seem to be related to autism (e.g., the experience of a natural disaster, loss of a loved one), whereas others, albeit surprisingly, do not (e.g., physical abuse).

An answer to these discrepant findings may lie an argument supported by many autism researchers: that autism is a conglomeration of several distinct subtypes, each with their own genetic and behavioral profile. If there exist specific subtypes of autism, is it possible that one risk factor may contribute to one subtype while not influencing the occurrence of another?

A recent paper published in the Journal of Autism and Developmental Disorders asks this very question. Janne Visser and colleagues from Radboud Unversity in The Netherlands argue that defining autism broadly versus narrowly affects which risk factors seem to have a significant impact. In their study, research participants underwent an extensive diagnostic protocol, including the standard diagnostic measures for autism (ADI-R and ADOS) as well as several other diagnostic tools. Following the diagnostic protocol, participants were classified as either having autistic disorder (AD), a narrowly defined diagnosis, or pervasive developmental disorder-not otherwise specified (PDD-NOS), a more broad diagnosis. Parents of these children and those of matched controls completed a survey with questions pertaining to many pre- and perinatal risk factors.

The most robust finding in this study was an expected one. When the AD and PDD-NOS groups were combined into one autism spectrum disorder group, this group demonstrated an increased occurrence of several risk factors, including maternal infections, prenatal stress, and low birth weight, as compared to the control group. The occurrence of these risk factors was also related to the severity of core autism symptoms, such as repetitive behaviors and impairments in communication.

Interestingly, however, when the AD and PDD-NOS groups were compared to each other, one risk factor, smoking during pregnancy, stood out as being significantly related to PDD-NOS, but not AD. Smoking during pregnancy was also related to lower IQ, but only in the PDD-NOS group, a finding that remained even after controlling for birth weight, which is commonly affected by smoking. This distinction between two autism subtypes provides support for the argument that subtypes of autism (narrowly versus broadly defined) may have different environmental and genetic influences.

Smoking during pregnancy is also a risk factor associated with ADHD, suggesting that this disorder may have underlying mechanisms similar to those of PDD-NOS, but not of AD. These mechanisms may be more than environmental, as Visser and colleagues propose. Smoking during pregnancy may be associated with specific genetic traits that can be passed from mother to child. These traits may contribute to the development of disorders, such as PDD-NOS and ADHD.

Why smoking during pregnancy wasn’t related to AD remains to be seen. It’s clear, however, that future studies should examine risk factors as they relate to not just autism in general but to specific subtypes of this disorder. Fortunately, the subtypes argument is being supported increasingly in the field of autism research. Although it begs more questions about each subtype and its associated characteristics, the subtypes argument provides a more focused and realistic approach to studying the true spectrum that is autism.

Autism or the Lack Thereof

Can you see the figure on the left within the figure on the right? (hint: try looking at the lower left corner of the figure on the right).  In a journal article published last month, Michael Spencer and colleagues from Cambridge explained that while people with autism perform normally on tasks like this one, they demonstrate deficits at the level of brain activation while performing such tasks.

The authors state that people with autism demonstrate a failure to deactivate certain brain regions that make up the default mode network when performing complex tasks like the one pictured. These regions, including the prefrontal cortex and the posterior cinguate cortex, may be collectively responsible for abstract mental activities like day dreaming. Why would deactivating the default mode network be important when performing complex tasks?  In a way, taking certain parts of the brain offline clears the air from distracting thoughts, allowing one to focus on the task at hand.

What’s interesting is that the authors not only found this failure to deactivate in people with autism but also in their siblings who don’t have autism.  In other words, when performing a task similar to the one above, the brain activity of brothers or sisters of people with autism looks more autistic-like than typical.  The authors present this finding as a potential endophenotype, or marker for familial risk, of autism.  Though this finding is only preliminary, it shows that siblings of people with autism (who share some genetic similarities with their siblings) may display certain traits that are indicative of autism, without actually having the disorder.  If this concept holds, it could provide a better picture of what goes on genetically in autism, or in the lack thereof.

SfN 2012 – Highs, Lows, & Beignets

Last week, I had the opportunity to attend the 42nd Annual Meeting for the Society for Neuroscience (SfN) in New Orleans.  For a quick frame of reference, imagine over 28,000 lovers of brain science toting 3 x 5 posters  and joining together for one of the largest academic conferences in the world.  From the staggeringly enormous poster hall extending from row A to row FFF to the sheer volume of information being shared in various special lectures, symposia, minisymposia, and (oh yes) nanosymposia, this meeting is surely a handful and, most definitely, a wonderful head-ful.

This was my second time to attend the meeting, making my experience infinitely more enjoyable.  Not to mention, this year’s Neuroscience 2012 App was super helpful for the iProduct obsessed #guilty.  Last year’s experience was so overwhelming I couldn’t even muster up a blog post to recount the meeting.  This time, I’ve at least managed to retain enough information to share about some brief highs, lows, and my newfound love for Beignets.

Highs:  

I was able to check out several posters relevant to our work in lab.  For instance, one group from Medical University of South Carolina presented work on graph theoretical analysis of resting state fMRI data in autism.  Sound familiar?  Interestingly, they found that individuals with autism  displayed less long-range connections forming in brain networks from childhood to adulthood, further supporting the functional underconnectivity hypothesis in autism.  Our whole lab was also intrigued by work from Tracy Bale’s group at Penn showing that early life and adolescent paternal stress can lead to stress pathway dysregulation in offspring in mice.   This finding adds a twist to the already complex picture of maternal stress in autism.

Another high was having the work our lab presented featured on the Simons Foundation Autism Research Initiative website: http://sfari.org/news-and-opinion/conference-news/2012/society-for-neuroscience-2012/anxiety-drug-enhances-brain-connections-in-autism. Talk about making my day.

I also got to attend several lectures at the meeting.  During her talk, Amy Arnsten of Yale discussed how chronic and acute stress can cause both structural and functional changes  in the prefrontal cortex (our decision making/judgment call part of the brain), effectively taking it “offline” during stress exposure.   Barbara Sahakian of Cambridge gave a lecture on the ethics of so-called “smart drugs.”  Most strikingly, she shared about the increasing off-label use of stimulants, such as the anti-narcolepsy drug modafinil, to improve cognitive performance.   She even showed how easy (and illegal) it is to purchase these prescription drugs online.

Lows:  I’m sure that by now most people have heard of and been baffled by the University of Chicago professor’s Facebook blunder.  I don’t need to justify this man’s misstep with a rant about women in science, etc.  Just know that if there was a “low” from SfN 2012 (or for society at large) this one definitely makes the cut.

Beignets:  How can I describe the powdery fried goodness that was my first taste of a beignet from Cafe Du Monde?  Let’s just say that my powdered sugar moustache was worn proudly and that I may have come home with some mix for my husband.