Rossignol DA, Frye REA review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation,inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposure.Mol Psychiatry. 2011 Dec 6. doi: 10.1038/mp.2011.165

This is a wonderful review article describing physical biomarkers and pathology in patients with autism.  Link to full text is above.

J Immunotoxicol. 2011 Jan-Mar;8(1):80-94.

Theoretical aspects of autism: biomarkers--a review.

Ratajczak HV.


Autism is dramatically increasing in incidence and is now considered an epidemic. There are no objective means to diagnose the disorder. Diagnosis is made subjectively, based on the perceived behavior of the subject. This review presents an approach toward development of an objective measure of autism. Covering the literature from 1943 to the present in the PubMed and Ovid Medline databases, this review summarizes evidence of hormones, metabolites, amino acids, and other biomarkers present in significantly different quantities in autistic subjects compared to age- and sex-matched controls. These differences can be measured in the gastrointestinal, immunologic, neurologic, and toxicologic systems of the body, with some biomarkers showing ubiquitous application. In addition, there are unifying concepts, i.e., increased vulnerability to oxidative stress, immune glutamatergic dysfunction, and pineal gland malfunction. The variances of the biomarkers from the norm present the opportunity to create biomarker arrays that when properly developed and analyzed could result in an objective diagnosis with a ranking of the severity of autism for each subject. The contribution of each biomarker to the overall diagnosis could be calculated, thus providing a profile pattern unique to the individual. This profile could consequently provide information for therapeutic interventions on an individual basis.

Altern Med Rev. 2010 Mar;15(1):15-32.

Biomarker-guided interventions of clinically relevant conditions associated with autism spectrum disorders and attention deficit hyperactivity disorder.

Bradstreet JJ, Smith S, Baral M, Rossignol DA.

Director, International Child Development Resource Center; adjunct professor of pediatrics, Southwest College of Naturopathic Medicine. Correspondence address: 3800 W. Eau Gallie Blvd., Melbourne, FL 32934; phone: 321-259-7111. Email:

Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are common and complex neurodevelopmental conditions. Diagnostic criteria for these conditions have traditionally relied solely on behavioral criteria without consideration for potential biomedical underpinnings. Newer evidence, however, reveals that ASDs are associated with: oxidative stress; decreased methylation capacity; limited production of glutathione; mitochondrial dysfunction; intestinal dysbiosis; increased toxic metal burden; immune dysregulation, characterized by a unique inflammatory bowel disease and immune activation of neuroglial cells; and ongoing brain hypoperfusion. Many of these same problems are common features in children with ADHD. These medical conditions, whether co-morbidities or etiopathogenic, would be expected to have synergistically negative effects on the development, cognition, focus, and attention of affected children. It is likely these biological abnormalities contribute significantly to the behavioral symptoms intrinsic in these diagnoses. However, treatment for these underlying medical disorders is clinically justified, even if no clear immediate behavioral improvements are observed. This article reviews the medical literature and discusses the authors clinical experience using various biomarkers for measuring oxidative stress, methylation capacity and transsulfuration, immune function, gastrointestinal problems, and toxic metal burden. These biomarkers provide useful guides for selection, efficacy, and sufficiency of biomedical interventions. The use of these biomarkers is of great importance in young children with ADHD or individuals of any age with ASD, because typically they cannot adequately communicate regarding their symptoms.

Novel plasma phospholipid biomarkers of autism: mitochondrial dysfunction as a putative causative mechanism
Pastural E et al.
Prostaglandins Leukot Essent Fatty Acids. 2009 Oct;81(4):253-64. Epub 2009 Jul 15.

Autism is a neurological disorder that manifests as noticeable behavioral and developmental abnormalities predominantly in males between the ages of 2 and 10. Although the genetics, biochemistry and neuropathology of this disease have been extensively studied, underlying causal factors to this disease have remained elusive. Using a longitudinal trial design in which three plasma samples were collected from 15 autistic and 12 non-autistic age-matched controls over the course of 1 year, universal and unambiguous alterations in lipid metabolism were observed. Biomarkers of fatty acid elongation and desaturation (poly-unsaturated long chain fatty acids (PUFA) and/or saturated very long chain fatty acids (VLCFA)-containing ethanolamine phospholipids) were statistically elevated in all autistic subjects. In all 8 of the affected/non-affected sibling pairs, the affected sibling had higher levels of these biomarkers than the unaffected sibling. Exposure of neurons, astrocytes and hepatocytes in vitro to elevated extracellular glutamate levels resulted in lipid biomarker changes indistinguishable from those observed in autistic subjects. Glutamate stress also resulted in in vitro decreased levels of reduced glutathione (GSH), methionine and cysteine, in a similar way to the decreases we observed in autism plasma. Impaired mitochondrial fatty acid oxidation, elevated plasma VLCFAs, and glutamate toxicity as putative causal factors in the biochemistry, neuropathology, and gender bias in autism are discussed.