Interlocking Causes of Autism

Why can’t we find the one cause of autism?  Because… we are searching for what does not exist, the “one” cause.  Autism remains a mysterious complexity and much of that complexity may lie in the fact that multiple causes may lead to it.  Furthermore, multiple processes interact to produce what we see in children. Dr. Rossignol and Dr. Frye collaborated to provide a wonderful review of autism research in regards to three factors which appear to play lead roles in this horrible affliction.  Many lines of research have pointed us towards oxidative stress, mitochondrial dysfunction, and brain inflammation as well as their interactions.

While a frustrating distance away from complete understanding, examining autism through the lens of these three metabolic processes has revealed a great deal of beneficial insight.  Considering the inherent difficulty of studying a brain based disease in children (very few samples of brain tissue being the primary obstacle), it is a wonder we know as much as we do.  Besides direct examination of brain tissue, newer radiology methods and biochemical testing procedures allow us to measure cell activities going on at a molecular level.  We have also learned more about the immune system in the brain than we ever imagined existed.

In terms of oxidative stress, several studies have uncovered connections between our bodies’ ability to handle the chemical stress our bodies produce or undergo constantly.  Oxidative stress refers to biochemicals in cells that oxidize surrounding molecules, kind of like rusting iron.  Typically this oxidative tendency damages surrounding cell molecules, including fats, proteins, and DNA.  Such damage slows, lessens, or stops functioning as well as causing cellular aging, even cancer.  The review paper’s authors provide a tasty list of further articles to read about each research contribution.  They noted that several different brain areas of autism patients have been implicated in this oxidative process.  Oxidative damage leads to nerve cell dysfunction and thus brain dysfunction in autism.

In terms of mitochondrial dysfunction, several other studies, also listed by the authors, implicate our cell’s powerhouses in the causation of autism.  The electron transport chain (ETC), the tri-carboxylic acid cycle (TAC) and differences in mitochondrial gene expression have all been discovered as contributors.  The mitochondria are the organelles (cellular mini-organs) in which organisms take carbs, proteins, or fats and burn them to make ATP for energy.  They first cycle cellular fuel through the TCA cycle to produce reactive electrons (tiny negatively charged particles) which then walk through the ETC where they drive sub-cellular motors to make ATP.  Differences have been found in the function of these processes as well as differences in which genes are activated and how much of the gene product is produced.  Brain cells without properly functioning mitochondria can wreck havoc on the mental functioning in not only autism, but other neurologic diseases like Alzheimer’s and Parkinson’s.

In terms of the immune system’s contribution to autism causation, the authors walk through a number of studies describing different research findings.  Using brain tissue and spinal fluid samples, researchers reported increases in immune hormones called cytokines, changes in which genes were expressed, elevated markers of inflammation, and visible changes in microglia (brain immune cells) activation.  With the growing recognition that inflammation plays a major role in other neurologic dysfunctional conditions, the role of the immune system in autism should not surprise anyone.  With multiple cytokines and corroborating markers to support this role, we have to keep digging into this area to find means of helping these children.  Somehow these microglia are behaving differently in autism and thus causing our nerves to function differently.  If we can understand the how and why, maybe we can alter their course, restoring function (in some cases we already do this with functional medicine).

By the end of the article, I am pleased to know that research presses forward towards helping children with this debilitating condition.  While functional medicine already recognized the roles of oxidative stress (including glutathione function), mitochondrial dysfunction (common finding in patients), and inflammation (possibly the most obvious), we functional MD’s do desire to sharpen our tools and utilize whatever means available to help our pediatric patients and their families. The long list of further reading the authors provide will hopefully have more nuggets of wisdom to help my patients live a healthier more abundant life.

Front. Physiol., 22 April 2014 |

Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism

Daniel A. Rossignol1* and Richard E. Frye2

  • 1Rossignol Medical Center, Irvine, CA, USA
  • 2Department of Pediatrics, Arkansas Children’s Hospital Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA


Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.

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