(Author’s note – I’m indebted to Professor Richard Deth of Northeastern University for sending me this article.)
The title may be long and confusing, but the findings are what many have been hoping to discover for years. (Novel Plasma Phospholipid Biomarkers of Autism: Mitochondrial Dysfunction as a Putative Causative Mechanism, Prostglandins Leukotrines Essent. Fatty Acids (2009) (HERE).
Given the profound differences in behavior and cognition in children with autism it's only reasonable to believe there must be some trace in the body of what makes these children so different.
Researchers in Canada working for Phenomenome Discoveries, Inc. and the Jonty Foundation out of Saint-Paul, Minnesota believe they may have found the answer.
In prefacing their study the researchers noted, “Neuropathological studies in autism have shown increased microglial activation, decreased cerebellar Purkinje cell density and abnormal brain swelling, particularly in white matter. Biochemical studies have shown increased oxidative stress, abnormal glutathione metabolism, decreased melatonin, and increased docosahexaeonic acid (DHA) in autistic subjects. Although there is debate as to whether autism has a pre- or post-natal origin, it is generally accepted that the symptoms and pathology persist through the life of the subject. These studies suggest that there is an underlying and ongoing biochemical abnormality in autism, regardless of its origin.”
The study conducted by the researchers was designed to find evidence of metabolic dysregulation and toxicity, regardless of the initial cause. Their plan was to collect three plasma samples over the course of a year from 15 autistic and 12 non-autistic age-matched controls. 8 out of the 12 controls were siblings of autistic children, some of whom had impairments in social relations not rising to the level of autism.
The researchers found “consistent alterations in the levels of very long chain fatty acid (VLCFA)-containing phosphatidylethanolamines (PtdEtns) and in DHA-containing ethnalomine plasmalogens (PlsEtns). . . These findings are reported herein and suggest a possible disruption of fatty acid metabolism due to compromised mitochondrial function. Mitochondrial stress was assessed through measurements of reduced glutathione (GSH) and related metabolites. In addition, we investigated and compared the in vitro effects of glutamate toxicity on neuronal, astrocyte and hepatocyte cell cultures to biomarker changes observed in the autistic subjects. Impaired mitochondrial fatty acid oxidation as the underlying cause of elevated plasma levels of VLCFA-containing PtdEtn is hypothesized.”
In plain English, what does this mean? First, the researchers found abnormal levels of very long chain fatty acids in children with autism. Second, it may be due to the mitochondria not working as well as it should (I'd also suggest involvement of the peroxisome). Last, the glutamate derangement which would result from this situation would have different effects on different parts of the brain.
All of the autistic subjects had significantly elevated plasma levels of long chain fatty acids A curious finding was also uncovered in relation to the siblings of the children with autism. “In all eight sibling pairs in which a non-autistic sibling was available for comparative analysis, the autistic child had more pronounced VLCFA lipid changes than the non-autistic sibling. Out of these controls, five showed some impairment in social cognition. When studied as a separate group, they displayed higher levels of lipid markers relative to non-impaired controls. These results suggest that the lipid biomarkers are also indicative of risk in that siblings of autistic subjects are considered to be “high-risk” controls and may share some phenotypic traits of the syndrome.”
In their discussion the researchers observed that their results “indicate that chronic mitochondrial stress is pervasive in autism and that elevated levels of fatty acid elongation and desaturation products are useful metabolic biomarkers of both mitochondrial stress and autism.”
The question of how glutamate may adversely affect the brain was addressed by the researchers. “Glutamate was used for the following reasons: it plays a major role in microgliosis, which is pervasive in autism; its ability to deplete glutathione is well-documented; and it has been reported to impair mitochondrial beta-oxidation, which is central to our hypothesis.”
In their experiments with glutamate on various brain cells they found “In all cell culture assays performed on hepatocytes, neurons and astrocytes, glutamate exposure resulted in a decreased 16:0 mitochondrial beta-oxidation, an increased peroxisomal processing of 16:0 and cytosolic fatty acid elongation/desaturation, as evidenced by an increased DHA-PlsEtn to 18:3-PtdEtn ration. Based upon these studies, the origin of the biomarkers we observed in autism plasma is hypothesized to be the result of impaired mitochondrial function.”
In their conclusion the authors stated, “the data presented herein indicate that a common metabolic phenotype is present in autism, and that this phenotype can be easily measured from a blood sample. This metabolic phenotype is characterized by elevated plasma levels of VLCFA-containing lipids arising from impaired mitochondrial fatty acid beta-oxidation. We further speculate that the elevated plasma VLCFA could be causal to the pervasive microglial activation observed in autism via a mechanism previously established in X-ALD. (X-linked adrenoleukodytrophy is a disease which has been studied extensively by the Peroxisomal Disease Laboratory of the Kennedy-Krieger Institute/Johns Hopkins.) Glutamate, a known neurotoxin that is excreted by activated microglia was shown by direct experimentation to reproduce the observed metabolic phenotype in liver, neuron, and astrocyte cultures. A thorough literature review of autism and glutamate revealed that glutamate toxicity arising from neuroinflammation is consistent with all known biochemical, pathophysiological and epidemiological data in autism.”
Although this study was small in nature and leaves many questions unanswered, such as the cause of the neuro-inflammation, it provides potentially breakthrough information. If the level of very long chain fatty acids can provide a clear biomarker for autism we will not only have a way to diagnose, but we'll also know the direction that research should proceed to find a cure.
For further information on the possible connection of autism to very long chain fatty acids you can look at my previous article on the subject HERE.
Kent Heckenlively is Legal Editor for Age of Autism