The Center for Disease Control and Prevention defines Autism Spectrum Disorder, or ASD, as a developmental disability caused by differences in the brain. It’s defined by the National Institute of Mental Health as a neurological and developmental disorder that influences how individuals interact with others.

A Response to the Huberman Lab Podcast

A couple of days ago, I listened to the Huberman Lab podcast episode that focused on the causes and treatments for autism with Dr. Karen Parker, Professor of Comparative Medicine at Stanford University and Director of the Social Neurosciences Research Program. Neuroscientist and Doctor Andrew Huberman asked Dr. Parker if she thinks that autism is a brain disorder or a disorder that happens to impact the brain.

This question interested me. I have thought about this alot since I heard this question and I wanted to do some research of my own. The brain-based approach would say that each autistic behavior is a result of specific brain regions as determined by genes. Proponents of this would say that autism genes target the brain. The more systemic approach says that neural system issues would be due to problems in connectivity but also due to more localized abnormalities and connections. Proponents of this idea would declare that autism genes are intended to target signaling and metabolic pathways that could affect the brain.

Derived from (Herbert, 2006)

In my opinion, I think ASD is rather more systemic, pertaining to a more generalized view rather than one that is localized to a particular part, like the brain. ASD is a disorder that manifests itself differently across different groups of people which shows the heterogeneity of the disorder. There are these dissimilar parts that are all somehow connected in a more systemic manner. 

The Neurological Basis of Autism

Most ASD research has focused on abnormal brain connectivity in that there are structural and functional factors related to the brain that present itself in observable behaviors. But this is only the beginning for ASD research. There are still so many questions we could ask. Do cellular disturbances cause connectivity issues that could produce ASD? Is impaired neuroconnectivity found in all subgroups with ASD?

We obviously know that the brain is implicated in ASD. There is no doubt. There are neuroanatomical alterations that we know are associated with autistic-like behaviors. For example, we know that the amygdala is larger in younger children with autism and does not go through the age-dependent size increase that is seen in neurotypical children. However, there is more research showing that the biological issues surrounding ASD aren’t specific to the brain. In fact, increased volumes of the brain as a whole haven’t fit models of brain-behavior correlation.

Since autistic individuals may suffer from other challenging issues that are beyond the scope of behavioral abnormalities, like gastrointestinal problems, sleep disorders, and seizures, there seems to be more nervous system abnormalities rather than neural system issues localized to the brain. Yet, these comorbidities that are seen so frequently aren’t even accounted for in diagnostic criteria. We know that every case of autism presents itself differently in each individual. I mean about 90% of autism cases are ascribed to idiopathic genetic variations – or ones that may occur more spontaneously and make autism architecture incredibly complex. If one individual may have more systemic issues than behavioral issues, could they be misdiagnosed with another disorder? Should we broaden our diagnostic tools to expand for more physical issues? Why haven’t we done this sooner? Is autism broadening more epidemiologically? It’s safe to say I have a lot of questions that I will continue to ask but I want to continue focusing on the more systemic model.

Is Maternal Immune Activation the Answer?

One idea that I thought of was maternal immune activation, or MIA. This idea proposes that inflammatory issues in utero, during pregnancy, can affect neurodevelopment and immune functions in the baby. In other words, there are two sides to this that are explained by two different approaches to autism: (1) MIA impacts the neurodevelopmental trajectory directly versus (2) abnormalities in immune pathways impact embryo neurodevelopment. The latter is more systemic, showing that brain alterations are due to other areas of the embryo or the uterine environment that are impaired.

I want to consider folate, a vitamin that plays a pivotal role in neurodevelopment and development as a whole. Folate concentrations in the fetus rely on mechanisms to transport it through the placenta and the brain. However, folate receptor antibodies can inhibit this transport and there are significant correlations that show the increase in the antibody inhibitors can affect the severity of ASD symptoms. This research strengthens the role of the immune response and folate metabolism on neurodevelopment. This is further proved by butyrate, a short-chain fatty acid, that can cross the blood-brain barrier and has anti-inflammatory and neuroprotective effects. In ASD, there are low levels of butyrate, causing mitochondrial dysfunction that is associated with neuroinflammation and other neurodegenerative diseases. 

Overall, there is an undeniable biological basis of ASD. These biological biomarkers could cause neuroabnormalities. In any sense, I support a bio-psycho-social approach which explains ASD in a more interconnected way. Since this idea is so supported in multiple facets of literature, I think there should be more clinical applications with this theory, creating tools to describe ASD more complexly and expanding diagnostic approaches. 

References

Herbert, Martha. (2006). Autism: A brain disorder or a disorder that affects the brain?. Neurotoxicology. 7248126334.