Different Types of ASDs: What Do Co-Occurring Conditions Have to do With It?

By Alycia Halladay, PhD
ASF Chief Science Officer

If you missed it, on Tuesday the workgroup on Under-Recognized Co-Occurring Conditions in ASD of the Interagency Autism Coordinating Committee met to discuss the current issues and start to lie out a research agenda. This workshop was aimed to have an honest exchange of views to help direct research – the IACC does not directly fund research itself.   It’s a way for researchers and funding agencies to discuss priorities and opportunities. The meeting was webcast live and will be archived on the NIH webpage, when the link is live we’ll post it. In the meantime here is what was discussed.

From the very first set of presentations it was clear that this issue is, like everything else is autism, complicated and messy. Four different presenters using different datasets all showed consistent findings of an increase in neurological (seizure), gastroenterological (GI distress) and psychiatric (ADHD and anxiety) comorbidities in ASD. The designs ranged from parent report, to pediatric registries, to health records that spanned through adulthood, to claims data from a number of different databases. And amazingly, while they actual numbers may be different, the trends in the data are the same. Many researchers pointed out that variability in the numbers could be because diagnostic practices – and that they could be under recognized or misdiagnosed.

Unfortunately, in the past these symptoms have not been well addressed by clinicians or even researchers. They are sometimes the most distressing and in the case of seizures, medically challenging. Sadly these comorbid problems can make ASD symptoms worse. Dan Coury gave the example of sleep – if you don’t get good night’s sleep, your “daytime” behavior changes. Beth Malow pointed out that in a brain of someone with ASD that is wired differently, sleep depravation causes even greater emotional problems. Larry Scahill from Emory presented on triggers for anxiety in people with ASD. These include peer relationships, different sensory stimulation. They are typically different than in typically developing people and the way people with autism express anxiety is different. Multiple co occurring conditions can mean multiple medications, which can lead to even more co occurring conditions. For example, some antipsychotics, used for impulsivity and aggression in ASD has been linked to obesity. Treating one symptom may cause another condition, which may be why people with co-ocurring medical conditions take on average, 5 different medications.

Another co-occuring symptom that is seen in a subgroup is immune dysregulation. Some individuals with ASD have an either overacting or underresponsive immune system, leading to anything from allergies to some GI problems. This means their immune systems react too much, or not enough, when faced with a normal challenge. A group at UC Davis linked to a particular part of the immune system to increased self-injurious and highly repetitive behaviors, and in one study, regression.

One of the presenters, Isaac Kohane from Harvard performed some statistical tools to identify subgroups using one of the large datasets mentioned earlier. For example, those that had seizures almost every day, or those that suffered from persistent infections including ear infections. He suggested that these subgroups might be meaningful in terms of treatment approaches, and even to understand the disorder better.

So what kind of treatments are we talking about? The overarching goal is to treat the co-ocurring condition to improve ASD symptoms. But right now, we aren’t even sure that the current treatments for these conditions are appropriate for those in ASD.

At the end of the meeting, we come back to the question – are these “co-occurring” conditions that are different entities or actually part of ASD itself?   Evidence from genetics shows overlap between genes linked to ASD, ID, OCD and anxiety. Is it possible that these “co-occurring” conditions may all result from the same underlying mechanism, and therefore co-occurring and core symptoms of ASD are responsive to similar treatments? Scientists have been searching for a very long time for a biological mechanism that can separate out different “types” of autism and it hasn’t happened yet. Maybe it is time to take a different approach – and maybe this is the right way to go.

 

Can “Sticky Mittens” Jump-Start a Baby’s Brain?

by Klaus Libertus, PhD
Research Associate at the Learning Research and Development Center
University of Pittsburgh

In a study published this week in the journal Frontiers in Psychology we were able to encourage grasping behaviors in three-month-old infants with a family history of Autism Spectrum Disorders (ASDs). This was done by using “sticky mittens” – infant mittens with Velcro attached, to be used with toys that also have Velcro attached. While wearing these mittens, a baby can swipe at a toy and the toy will stick to the mitten – giving the child the experience of actually picking up the toy. You may wonder why one should study the effects of a motor intervention in infants at risk for ASDs – since ASDs are typically defined by the presence of social rather than motor delays. The answer is quite simple, early motor skills are necessary for social interactions. Let me explain.

Successful grasping of objects typically emerges around 5 to 6 months of age. However, rather than the act of grasping itself, what matters more is what happens next. Once a toy has been picked up, the child can explore the object, show it, and share it with others. Parents respond to these behaviors by labeling the object or by encouraging the child’s actions (e.g., by saying “good job, you got the ball”). In short, grasping an object places the child in the midst of dynamic social interactions that are rich in opportunities for learning about social cues and language.

Agreeing with this interpretation, previous work from our lab has shown that encouraging infants’ grasping skills also leads to an increase in their attention towards faces – at least in infants without a family history of ASD. This finding suggests that obtaining a new motor skill may indeed affect development of social skills. In the context of ASDs this is of particular interest, as a growing number of studies have identified motor issues such as poor postural control in infants with a family history of ASD. For example, we recently reported in the journal Child Development that at-risk infants show reduced grasping activity at six months of age. Together, these findings suggest that infants at high risk for ASD may benefit from early interventions targeting the motor domain – especially their grasping skills.

  Our new study addressed exactly this question and brings both good news and not so good news. Overall, our at-risk three-month-olds increased their grasping significantly following motor training – suggesting that at-risk infants will respond to motor interventions. Unfortunately, the same children did not show a meaningful increase in attention towards faces following training – unlike our findings in infants without a family history of ASD. There are different possible explanations for these diverging findings: On the one hand, it is possible that our at-risk infants simply needed more time to learn about the social interactions that follow grasping. On the other hand, it is also possible that there were some infants in our sample who performed worse than the others and reduced our ability to detect changes in the entire group. To examine this possibility further, we currently follow the group of trained at-risk infants to see if their response to our motor training may eventually predict a future ASD diagnosis.

Despite our negative results regarding the social attention task, our findings are encouraging and show that motor interventions can be effective in at-risk children. A key aspect of our intervention was that the parents themselves provided the training. Since parents know their child best, they can uniquely tailor interventions to their child’s specific needs and constraints – significantly improving the effectiveness of the training. Another intervention study that was published this week follows the same approach, and future research should place more emphasis on including the parent when designing and implementing interventions.