Yale, Autism and Morphology

  

In a recent post I introduced a new term – morphology.  Some scientific jargon serves to make things more confusing for the lay reader, but this really is a useful term to understand autism.

Morphology, in biology, the study of the size, shape, and structure of animals, plants, and microorganisms and of the relationships of the parts comprising them.

Today we are talking about morphology as it relates to the growth of the human body in autism.

In earlier posts relating to hormones and growth factors (endocrinology) I made my own observations about Monty, aged 11 with ASD.  I commented how he fell from the 80% percentile in height, aged 2, to the 20^th percentile, where he is now.  I also noted how he went from very muscular to your average “floppy” toddler.

I did discuss this with a pediatric endocrinologist and asked what is the point of collecting this height and weight data for children, if nothing is done with it.  I did tell her all about the emerging use of the growth factor IGF-1 in treating autism and also the hypothesis that people with autism have low thyroid hormone T3 in the brain.

I concluded that endocrinologists do not know anything about autism, but I did learn all about bone age. 

Endocrinologists often use X rays of the hand to look for advanced or delayed bone age.  They look at the gaps in between the small bones to assess the degree of maturation.  The bigger the gap, the less mature the bones.  They have a big book of X-rays and they just flip through the pages until they find one like your X ray.  So if you are 11 years old, with bone structure of a 9 year old, then you would have delayed bone age.  In practical terms, this means you are likely to keep growing for longer than the average child.

Autism Research

As we have seen already, much data in autism is of dubious quality.  Studies are contradictory.  Much of this is due to mixing apples with kiwis and even pineapples. You cannot usefully compare data on severely autistic people with those ever so mildly affected, but still “autistic” by DSM. Even separating early onset and regressive autism is rare in studies.  There is no agreement as to what regressive really means and some scientists even think regression is just a development plateau – I guess they never see actual patients.

So I was pleased to come across some interesting research about autism morphology that seems credible.  Of all places, it was in a student publication from Yale.  On Facebook, Monty’s older brother keeps getting confused with his namesake, who is one of the reporters on the Yale student newspaper.    Not only does Yale have a daily student newspaper, but it also has its own Yale Scientific Magazine.

They must have a lot of free time over at Yale.

This was my first experience of student journalism at Yale.  I was impressed.

Autism may be predicted by overgrowth

Sizing Up Autism: The CorrelationBetween Autism and Abnormal Growth

  

One identified phenotype associated with autism is abnormally large Total Cerebral Volume (TCV) and, correspondingly, Head Circumference (HC) – collectively called macrocephaly. Researchers at Yale University’s Child Study Center have undertaken studies in the connectivity of growth and neural development to assess risk and predict developmental phenotype of young boys through growth measurement. A group of 184 boys aged birth to 24 months, composed of 55 typically developing controls, 64 with ASD, 34 with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), 13 with global developmental delays, and 18 with other developmental problems, was analyzed for head circumference, height, weight, and social, verbal and cognitive functioning. Boys with autism were significantly taller by 4.8 months, had a larger HC by 9.5 months, weighed more by 11.4 months, were in the top ten percent in size in infancy (correlated with lower adaptive functioning and social deficits), and showed accelerated HC growth in the first year of life.  


Here is actual study:-

Early Generalized Overgrowth in Boys With Autism

Main Outcome Measures: Age-related changes in HC (head circumference),

height, and weight between birth and age 24 months; measures of social, verbal, and cognitive functioning at age 2 years.

Results: Compared with typically developing controls, boys with autism were significantly longer by age 4.8 months, had a larger HC by age 9.5 months, and weighed more by age 11.4 months (P=.05 for all). None of the other clinical groups showed a similar overgrowth pattern. Boys with autism who were in the top 10% of overall physical size in infancy exhibited greater severity of social deficits (P=.009) and lower adaptive functioning (P=.03).

Conclusions: Boys with autism experienced accelerated HC growth in the first year of life. However, this phenomenon reflected a generalized process affecting other morphologic features, including height and weight. The

study highlights the importance of studying factors that influence not only neuronal development but also skeletal growth in autism.

  

The Yale researcher is Polish, as was the lady who wrote about oxidative stress in the brain lowering D2 and hence thyroid hormone T3 in the brain.

Conclusion

This does take us back to the earlier posts on human growth factors.  It does seem that at least in one sub-type of autism there is “excess” growth in the first two years that is visible in terms of morphology.  This growth spurt then halts.

We already have data showing that in autism the brain itself also “over-grows” up to the age of about three.  We can now generalize that in this sub-type everything is likely affected by this over-growth.

Why does the growth spurt halt? It is not for lack of the growth factor IGF-1, many people with autism actually have elevated levels of this growth factor.  It is simple and inexpensive to check; I did it.

The problem may relate to something called Akt, also known as protein kinase B (PKB).

IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth and proliferation.

Very recent research has highlighted abnormalities in the IGF-1 – Akt pathway and also in similar pathways related to the brain’s own growth factor, BDNF.  (Note that mTOR is also implicated in autism)

Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autism spectrum disorders

 Abnormalities in BDNF/TrkB/PI3Ksignaling pathways in autism

So while IGF-1 may be an effective therapy for some people with autism (it is already used experimentally), most likely the real problem is slightly different and a better intervention might relate to AKT/PKB.

We will follow up on these and other protein kinase shortly.