Autism: A Brain Disorder or a Disorder that Affects the Brain?

M.R. Herbert and T. Arranga/Medical Veritas 3 (2006) 1182–1194


Autism research priorities have been shaped by underlying models. The model of autism as a genetically determined hard-wired brain disorder, dominant in recent years, has led to a search for “brain genes” and brain alterations. But this model has produced limited results, has rested on an over-interpretation of evidence for heritability, and has also failed to encompass multiple features of autism outside the behavioral definition, including systemic physiological changes (especially, but not restricted to, gastrointestinal and immune) and the increasing numbers of cases. A more inclusive model would construe autism as a disorder that affects the brain, and that is the outcome of complex interactions among factors related to genetic vulnerability, environmental triggers or causes, and epigenetic changes. This model can incorporate many recent findings, and it opens the field on several levels: to broader genetic investigations (including, for example, systemically expressed genes that could impact the brain secondarily), and to study of vulnerabilities beyond genetics at multiple physiological levels. Since the behaviors that define autism appear to be produced by brains affected by a variety of biological alterations, this more inclusive model is also better oriented to encompassing autism’s heterogeneity. It al-lows us to investigate what systems and network-level commonalities there might be among brain and body changes whose specific biological details may differ. Of paramount practical importance is that some features of systemic involvement may be modifiable. Thus, we may therefore more aggressively search for such features as potential treatment targets that may reduce suffering and improve options for affected individuals. By improving metabolic status, parameters modulating brain function (e.g., synaptic thresholds, connectivity, energy metabolism) may be affected in a favor-able way. This may account for some of the growing number of anecdotal reports of recovery from autism after integrative biomedical and behavioral treatment. Moving from a “genes-brain-behavior” to a “pathogenesis (genes, environment, epigenetics)-mechanism (molecular, cellular, tissue, processing)-phenotype (behavior, sensory-perceptual, cognition, medical)” model, which not only spells out the levels of the biological hierarchy, but also looks at all these levels developmentally, is a challenge to compartmentalized science, but this is what we need if we are to translationally connect research and successful treatment.

© Copyright 2006 Pearblossom Private School, Inc.–Publishing Division. All rights reserved.

Keywords: autism; environmentally responsive genes, phenotype, metabolism, epigenesis, biomarkers, integrative systems, systemic model, networks, translational research

Now please join me in welcoming Dr. Martha Herbert. Dr. Martha Herbert, M.D., Ph.D. is an Assistant Professor of Neurology at Harvard Medical School, a pediatric neurologist at the Massachusetts General Hospital in Boston and at the Center for Child and Adolescent Development of Cambridge Health Alliance and a member of the Harvard MIT MGH Martinos Center for Biomedical Imaging.

Prior to going to medical school she obtained a Ph.D. in the History of Consciousness from the University of California, Santa Cruz. She has received the Cure Autism Now Innovator Award and directs the Cure Autism Now Foundation’s Brain Development Initiative. She is the co-Chair of the Environ-mental Health Project of the Autism Society of America. Her research program includes studying what makes some autistic brains unusually large, how the parts of the brain are connected and coordinated with each other, how to incorporate metabolic biomarkers into brain research and how we can develop measures sensitive to changes in brain function that could result from treatment interventions.

Today we are learning more about concepts and findings from Dr. Herbert’s papers entitled, Autism: A Brain Disorder or a Disorder That Affects the Brain?” published in Clinical Neuropsychiatry in 2005 and her most recent paper, Autism and Environmental Genomics from Neurotoxicology.

Dr. Herbert, a pleasure to welcome you to Autism One Radio.

Thank you. Thank you for doing this.

Dr. Herbert, how are autism spectrum disorders currently defined?

Autism spectrum disorders are defined behaviorally—by behavioral criteria that you observe according to a set of standards that have been developed through extensive research on many individuals. But there are no biological markers. There’s no blood test, there’s no brain imaging test, there’s no EEG that can support the diagnosis. It’s a purely behavioral diagnosis.

So how much do autism’s behavioral features really tell us about autism’s biology?

Well, we really can’t answer that, but I suspect that it’s a pretty indirect route from the behaviors to the biology. What I mean by that is that there may be a number of different biological pathways that lead to similar behavioral features.

And you can’t reason back directly from the behavior to the biology, except possibly in certain circumstances. But we really don’t know because, for the most part, autism research hasn’t been measuring that biology.

Those are really good points, Dr. Herbert. Now, how many body systems seem to be involved?

That’s a very interesting question. And, you know, I’m wondering whether it’s always the same thing. Certainly the immune system and the gastrointestinal system feature prominently in many individuals. However, it may be that in different cohorts, in different countries, you may see different patterns. I’ve heard from some researchers that there are more gastrointestinal cases in England than in the United States. And I took a trip to Cuba and I found that people at the autism schools there were talking about lung involvement which I haven’t heard anywhere else. The bottom-line is that we really have very little systematic evidence on that.

I think that brings up a really important point and possibility to mind—that because they’re reporting a greater prevalence of GI involvement in England or lung involvement in Cuba, that gives us some more direction for research.

Well, these physical phenomena are tremendous cues—clues—I mean, both. They’re clues because they point; they’re clues and cues because they point us in directions where we can use, if we are courageous enough to do so, the biological information about those systems to help us understand what could be driving the problems.

Yes. And it kind of is a reminder to us, a cue as you said, to keep our thinking broad for the moment. Would you agree?

We really need to keep our thinking broad. I think when you don’t know what a disease process is you need to observe the phenomenology – which is just what… how it presents itself – very carefully without imposing models which would exclude certain factors on the basis of assumptions that maybe you haven’t proven yet.

Right. Science is supposed to go into things with an open mind and report what it finds rather than a limited presupposition?

Right. You’re supposed to describe carefully. There’s a natural history phase in the early periods of the development of domains of science where you mainly describe carefully, and the systematization comes after an extensive period of careful observation. I think that kind of careful observation has been supported in autism research to a significant degree in behavior, but we need it in the whole body approach to autism as well. We need it to be systematic; we need it to be supported.

Now, you go into a more systematic whole body approach in your paper entitled, “Autism: A Brain Disorder or a Disorder That Affects the Brain?” Why is it important to make the dis-tinction called for by that question that title of your paper?

I think we’re oriented very much in what we perceive – by what we think. We organize the information and the information


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