Herbert, M.R.,  Autism: From Static Genetic Brain Defect to Dynamic Gene-Environment-Modulated Pathophysiology. Chapter 10 of Genetic Explanations: Sense and Nonsense. Krimsky, S. and Gruber, J. eds, Harvard University Press (2012).

The chapter covers similar material to what is in the book THE AUTISM REVOLUTION, but pitched to upper-division undergraduate college students.

Here are the chapter’s Section Headers. Please get the book to read more and also to read the other terrific chapters!!

• Autism Status Quo: Genes, Brain, Behavior and Hopelessness
• Anomalies Undermining the Genes-Brain-Behavior Model
  • Not a Static Prevalence
  • Not Just Genes: Environmental Contributors.
  • Not Just a Few High-Impact Genes: Hundreds of Mostly Lower-Impact Genes.
  • Not Just Inherited Genes: De Novo Mutations.
  • Not Even Mainly Genes: Substantial Environmental Contribution.
  • Not Just Brain Genes
  • Not Just Local, Modular Brain Disturbances: Whole Brain Involvement.
  • Not Just Prenatal
  • Not Necessarily Present at Birth
  • Not Just Behavior
  • Not Just the Brain
  • Not Just Deficit: Giftedness and High Intelligence.
  • Not a Life Sentence: Evidence of Remission and Recovery.
• Dynamical Physiological Processes Implicated In Autism
  • Immune Dysregulation
  • Mitochondrial Dysfunction
  • Oxidative Stress
  • Methylation Disturbance
  • Disturbed Gut Microbial Ecology
  • Hormonal Dysregulation
• Active Pathophysiology, Genes and Environment
  • Active Pathophysiology and the Brain
  • Impact on Synaptic functioning
• Could Active Pathophysiology Be Impairing Connectivity?
• Does Active Pathophysiology Modulate Genetic Substrate Or Could It Be a Primary Cause of Brain Dysfunction?
• From Genes and Neurons to Environment and Glial Cells
• Cause?
• Modulating Severity by Treating Intermediary Metabolism
• Obstructed Rather Than Defective
• Environment: The Gift That Keeps On Giving
  • Hardware or Software?
  • From Developmental To Early Onset Chronic Pathophysiology
• From a Fixed Unitary Phenomenon to Modifiable Manifestations of Complex Interacting Systems Problems
  • Autism as an Epiphenomenon or Emergent Property of a Challenged System
  • Specific Genetic Determinants or Final Common Pathways of Pathophysiology?
• Time to Get a Grip
• Addressing an Apparent Epidemic Through a Praxis of Environmental Pathophysiology
• Beyond Autism

In my opinion the recent research paper, Differences in White Matter Fiber Tract Development Present from 6 to 24 Months in Infants with Autism (Am J Psychiatry 2012 ; 169 :589-600), reports a very important finding and represents a huge amount of work, but the study is quite incomplete both in what was chosen to be measured and how the findings are interpreted by the investigators, Jason Wolff et al.  Moreover, even though this study has been touted in the news as a way of detecting autism early, it really isn’t ready for prime time as a clear indicator of the autism diagnosis. I think this finding is about things that occur downstream of other biological factors that are driving these changes.  – And because these changes are downstream, they are fuzzier in that they reflect a mixture of lots of other influences.   This makes it hard for them to clearly demarcate risk from lack of risk.  Measuring what’s upstream might bring us closer to a clinically useful brain measure of autism risk in young infants.

Because I am a brain researcher, I spend a lot of time thinking about different techniques to measure things in the brain.  Let me explain to you why people study things like this, what was measured in this study, and what it means. Then I’ll be able to explain to you why this study is both important and incomplete.

Why people study babies at risk for autism with brain imaging

Autism is a neuro-developmental – and many would say also chronic – condition that is presently defined by behavioral criteria.   But these behavioral features don’t emerge in babies – they only become detectable when a baby becomes old enough to perform these behaviors.  The “holy grail” of autism research prominently includes being able to detect signs of autism, or autism risk, at a younger age than when current gold-standard tests can diagnose autism.  …

…

Concluding questions:

1. Is this study’s measure robust enough for us to march our 6 month old babies down to the local MRI scanner and test them for “autism”?  No, it is not.
2. What’s missing from this study? 
3.  Why did these highly trained, dedicated investigators design a study that did not look at these upstream factors that probably are driving these FA changes?  Two reasons:…
4.  What can we do about this?        READ MORE…

You could say this post is a long time coming. In the last few years, I’ve lost count of the huge number of emails I get from parents with kids who have special needs either asking for advice or explaining how The Primal Blueprint has made a significant difference for their children. These are parents who love their kids for all their abilities and differences and who want to explore every reasonable lifestyle intervention they can to make their kids’ lives everything they can and should be.

I’ll state the obvious here. I’m not a disability expert, but I’ve been moved and motivated by these parents’ emails. From a general health perspective, I’ve wondered how our modern lives could be contributing to the epidemic. Likewise, I’m curious how research can illuminate potential benefits of lifestyle interventions. What is the biological picture behind the dysfunction in these conditions, and how can biology be harnessed to restore functioning? A recent approach focused on the whole brain and whole body is asking those exact questions – and finding answers.           Read more: http://www.marksdailyapple.com/autism-a-brain-or-whole-body-disorder/#ixzz20cCn6APx

–from The Autism Revolution by Martha Herbert, MD, PhD, with Karen Weintraub (Ballantine Books, 2012)

Martha Herbert reasons in her remarkable book that the rapidly increasing prevalence of autism indicates the disorder can’t possibly be due to genetics alone. She makes the case, based on findings in diverse fields of medical research and on her own clinical experience, that autism is not a genetic trait destined to be lifelong. Instead, she’s suggesting that the rise in autism is a consequence of the environment we live in, and that many autism symptoms can be reduced by making environmental changes. It’s compelling reading whether or not someone you love has autism, because many of the environmental influences that probably contribute to autism will likely affect all of us in time.  Read more…..

Here is an excerpt from the blog:

This paper (entitled “Wild-type microglia arrest pathology in a mouse model of Rett syndrome“) is remarkable because it shows that our previous research into Rett syndrome – which primarily addressed dysfunctional neurons – was incomplete.  The mice in this study got better because they got new microglia that functioned better. The microglia they’d started with took a hit from the Rett genetic mutation and weren’t doing their job of “taking out the trash” from the neuronal environment. When the healthy microglia came into the system and started doing their job, the disease stopped getting worse and stayed stable – quite unlike the normal course of the condition.  When the scientists tested this idea by stopping the “garbage collection” role of the microglia, all the gains were lost and the mice got sicker.

Amazingly, nothing was done to the neuron itself in the intervention.  Just the microglia.  This suggests that the symptoms of the disorder might be driven by mischief related to the microglia, not just genetic insults to the neurons, as has been assumed.  Maybe the problem is the garbage created by the chaos and dysfunction from the gene mutations, not just (or even not mainly) the gene mutation’s impact on the neurons.

So is Rett Syndrome really “neuro”developmental? Or does that term mislead us and put blinders on our vision?  Doug Fields, author of THE OTHER BRAIN, a wonderfully readable book on glial cells, suggests as much.

If this is true, is it also possible that conditions like autism, which have also been assumed to be due to neuronal problems, might also be highly shaped by microglial problems? In the case of Rett Syndrome, microglia are messed up for genetic reasons.  In lots of other conditions, including autism, microglia may well be activated for some other reason — perhaps just environmental exposure since many exposures and infections can activate microglia.  This means that addressing environmental issues – improving food and reducing toxic exposures – may help a lot.

Even in Rett syndrome, where there is certainly a genetic problem, isn’t is possible that more toxic environmental exposures and poor nutrition could make things worse – or vice versa – could healthy environmental inputs improve wellbeing in meaningful ways, slowing the disease’s progression and making people with Rett syndrome less uncomfortable?  So often, doctors quite trying to look for ways to help when they find a gene – but even then, perhaps other things can still make life better.

To help microglia cells do better, we may not need to identify a specific molecule to target with a drug.  If we improve health – through taking care of optimizing food, avoiding toxins and infection and minimizing stress – as I lay out in my book The Autism Revolution: Whole Body Strategies for Making Life All It Can Be  – microglial cells won’t have to work so hard fighting off dangers and may be more effective at everyday housekeeping.   READ MORE…

Attending yet another conference I find myself thinking about paradigm whiplash.  It’s hitting me again.

Why there are so many different points of view in autism that don’t seem to overlap?  The IMFAR meeting May 17-20 (International Meeting for Autism Research, a major academic conference) was full of people aiming to find biomarkers for autism — looking mainly for genetic, neurochemistry, brain and behavior.  At AutismOne this week (5/24-27) and at the ARI (Autism Research Institute) conference at the end of April – we find lots more parents, a mostly different group of scientists, professionals and paraprofessionals , and more focus on biology beyond genetics: in particular, metabolism, immune system, nutritional problems – but not so much work on the brain.

Both conferences are brimming with new science.  Each scientific subculture produces lots of support for why they approach things the way they do – yet the overlap, the interplay, is weak.

It doesn’t work for me to just stay inside any one of these subcultures.  That just makes the paradigm whiplash worse.  Each has so much to offer, yet each alone is not enough.  Inside any single paradigm it is painfully apparent to me that important things are being missed.  This discomfort drove me to develop my website www.autismWHYandHOW.org , so I could put the different paradigms side by side in one place, and contribute to genuine discourse.

What gets me past “paradigm whiplash” is a “higher synthesis” – from the strengths of each point of view, each subculture.    And I organize my “higher synthesis” around what we can do RIGHT NOW to help the most people possible.  This is what I aimed for in my book The Autism Revolution.

I’d like to see the careful attention to study design, the meticulous refining of questions that we see so much of at IMFAR — and the ample research funding that makes this possible — be available on the side of the fence where families with autism live every day. Why is it that our important science is so often divorced from the daily experiences of autism and from helping people with autism live healthier lives? Why is it that the scientists and practitioners who sincerely make simple, safe biology-based attempts at healing the medical physiology of people with autism are so often dismissed as quacks and charlatans?

I’d like to see the IMFAR people learn from these pathophysiology (that is, biology challenges beyond genetics) people.  I’d like to see these IMFAR scientists engage with the whole-body, whole-brain, whole life of each person with autism.  This means both each person as an individual, and each person as complex.  Rather than staying just at the level that is most familiar to us, we all need to cultivate a mental zoom lens that can cruise in and out from the hidden levels molecules and metabolism to cells in brain and body, and from there to behavior and social/physical environment.  Considering that all of these levels have documented challenges in autism, we could do our best to help people with autism if we could form a comprehensive team that encompasses all of these levels functions collaboratively.   This is what will allow a synthesis of what the high-level scientists and the committed therapists are doing every day to get each person with autism as healthy and functional as possible.

Our common goal should be to help people with autism achieve their optimal potential (and even recover in some cases) by removing all obstacles possible and providing supports tailored for each person. This aim would help ground the IMFAR research in things that are actionable right now; and help us learn as much as possible from the on-the-ground successes of therapists, nutritionists, wellness-oriented doctors and parents.

This synthesis is possible, and even happening.  Geneticists now see that though genes may be handed us from birth, they get turned on and off by changes in what we do or what we are exposed to.  Even more, now that symptoms of syndromes associated with autism, like Rett and Fragile X, have been reversed in mouse models –– many scientists are starting to realize what observant clinicians and parents have already noted — that autism is a changeable state, not a hardwired trait.

More people are also starting to realize that autism is not a single “thing,” but a composite of many interacting systems – and that we can look for ways to help at many levels – aiming to help health and functioning.  When the parts get better the whole works better too.  For example, studies are also showing that metabolic and immune problems can increase risk. These kinds of problems can be helped RIGHT NOW by getting people with autism away from restricted diets and processed food and maximizing the nutritional content of diet. There is a flood of scientific literature supporting the role of diet in improving the kinds of physiological/biomedical problems people with autism face.

A higher synthesis for me would be:

• Turning clinical activities into scientifically usable data – not only behaviorally oriented interventions, but also treatments that address the individualized whole-body issues of people with autism as into scientifically usable data.
• Getting an aggressive public health program in place so that every pediatrician and primary care doctor can and will help every patient in their practice optimize their health and reduce their risk. And a parallel campaign ensuing that schools serve healthy food and parents have access to abundant low cost organic produce and meat/fish/poultry, so feeding their children helps rather than compromises young people’s health.   Tracking the impact this has on how well kids do in school, in therapies and at home.
• Convincing the research establishment to turn its attention and resources to questions raised by these incredibly common metabolic, immune and/or nutritional problems, and the fact that addressing these problems is one of the few means we have for helping people right now.
• Integrating genetics, brain, sensorimotor, behavior and pathophysiology investigations so that all aspects of individuals with autism can be understood in relationship with each other and so that help is coordinated and as effective as possible.