ASA's 37th National Conference on Autism Spectrum Disorders (July 13-15, 2006)

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Thursday, July 13, 2006: 1:30 PM-2:45 PM
553 A-B
#2292- Linking Emotional Stress with Oxidative Stress: Therapeutic Implications
Emotional stress associates with physical markers for oxidative stress, so behavioral training which emphasizes relaxation for children with autism may lower urinary isoprostane, a measure of lipid oxidation. Evaluation of urinary isoprostane levels in relation to behavioral therapy may serve to i) increase understanding of the role of oxidative stress in autism and ii) establish an objective biochemical measurement for the assessment of behavioral therapies.

Presenters:George Lambert, MD, UMDNJ-Robert Wood Johnson Medical School, UMDNJ-Robert Wood Johnson Medical School - Dr. George Lambert is the Director of the NIEHS/USEPA Center for Childhood Neurotoxicology and Exposure Assessment, which is located at the Environmental and Occupational Health Sciences Institute, a jointly sponsored Institute of Rutgers, The State University of New Jersey and UMDNJ-Robert Wood Johnson Medical School. Dr. Lambert is also an Associate Professor of Pediatrics, Director, Division of Pediatric Pharmacology and Toxicology at the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School - Piscataway/New Brunswick. He holds a B.S. in zoology from the University of Illinois, Champaign-Urbana (1968) and an M.D. from the Univ. of IL, Chicago(1972).

June Groden, PhD, The Groden Center - Dr. June Groden is considered one of the pioneers in the field of autism and developmental disabilities. Her primary areas of interest are stress and anxiety and procedures to reduce stress. She has focused on the development of relaxation and imagery based procedures for a population with autism and developmental disabilities. Dr. Groden is the Director of the Groden Center in Providence, Rhode Island.

Woody R. McGinnis, M.D., Oxidtive Stress in Autism Study, Research Coordinator - Dr. McGinnis was educated at Dartmouth College and the University of Colorado. After volunteer medical work in rural Peru, he practice general medicine in Arizona for many years. I 1993, Dr. McGinnis began studying nutritional influences on behavioral in order to help his own son, Ryan, and this extended to his practice. In 2001, he entered full-time research. He initiated and coordinates the Oxidative Stress in Autism Study, a first-of-its-kind university collaboration measuring a broad range of oxidative markers in the urine, blood and central nervous system of children with autism.

Matthew Goodwin, MA, The Groden Center, Research Coordinator - Matthew Goodwin, M.A. is a PhD candidate in the Behavioral Science program at the University of Rhode Island and the Research Coordinator at the Groden Center. His research and clinical experience with children with ASD focuses primarily on the single subject assessment of stress responses using telemetric heart rate monitors and digital video/editing systems.

When oxidants exceed the antioxidant defense, biological systems suffer oxidative stress, with damage to biomolecules and functional impairment. Lipids, proteins, glycoproteins, and nucleic acids are subject to oxidative injury, and a number of analytical methods exist for measurement of oxidative by-products in urine, blood, breath, and organ tissue samples.

It has been suggested that oxidative stress may play a role in the expression of autistic behavior [Ross 2000] [McGinnis 2004]. Endogenous anti-oxidant functions [Zoroglu and Armuctu 2004] [Chauhan and Chauhan 2004] [Golse and Debray-Ritzen 1978] [Yorbik and Sayal 2002] [James and Cutler 2004], and anti-oxidant nutrient levels [Raiten and Massaro 1984] [Isaacson and Moran 1996] [Audhya and McGinnis 2004] are depressed in children with autism. Greater free-radical production is measured in blood of children with autism [Zoroglu and Yurekli 2003] [Sweeten and Posey 2004] [Sogut and Zoroglu 2003] .

Oxidatively-damaged biomolecules are higher in autism, including red cells [Zoroglu and Armuctu 2004], serum [Chauhan and Chauhan 2004], and brain. Lipofuscin, a nonspecific marker for oxidative stress in brain, is elevated in cortex of children with autism [Lopez-Hurtado and Prieto 2005], and a specific marker for lipid oxidation and associated protein alteration (carboxyethylpyrrole, CEP) was consistently elevated in the cortical axons and dendrites of specimens from five children with autism [Perry and Saloman 2005].

Greater oxidative stress also has been implicated in Schizophrenia and ADHD. Both feature higher levels of oxidized biomolecules [Mahadik and Scheffer 1996 ] [Altuntas and Aksoy 2000] [Zabrodina and Osokin 1999] [Ross and McKenzie 2003], lower anti-oxidant nutrient levels [Suboticanec and Folnegovic-Smalc 1990] [McCreadie and MacDonald 1995], and behavioral improvement with anti-oxidant nutrient treatment [Bilici and Yildirim 2004] [Starobrat-Hermelin 1997] [Kutko and Frolov 1996] [Sandyk and Kanofsky 1993][Rachkauskas 1998]

Oxidative alteration of enzymes and structural components of cells is at least partially reversible when sufficient antioxidants are present [Webb 1966] [Stohs 1995]. Many medications used in the treatment of schizophrenia are, in fact, potently anti-oxidant. [Jeding and Evans 1995] ]. Treatment of children with autism with vitamin C [Dolske and Spollen 1993] or carnosine [Chez and Buchanan 2002], both recognized anti-oxidants, resulted in significant behavioral improvement.

Emotional stress in humans associates with higher biomarkers for oxidative stress. Emotional stress increases catecholamine metabolism, which increases oxidative stress by increasing the production of free-radicals. Similarly, academic stress [Eskiocak and Gozen 2005] or sleep deprivation [Everson and Laatsch 2004] associate with lower protective anti-oxidant levels in blood. Higher scores for Tension-Anxiety and perceived work-load correlate with higher oxidized nucleic acid levels in the blood of female workers [Irie and Asami 2002]. Higher protective anti-oxidant enzyme levels [Sharma and Sen 2003] and lower oxidized lipid levels [Schneider and Nidich 1998], were found in blood samples of meditation practitioners.

Immobilization-stress approximates emotional stress in animals, and associates with greater oxidative stress: increased free-radical production, decreased anti-oxidant enzyme levels, and increased oxidized lipids in tissues, including brain [Oishi and Yokoi 1999] [Liu and Wang 1996] [Olivenza and Lorenzo 1999] [Fontella and Siqueira 2005]. Sleep-deprivation of animals produces similar oxidative changes [Silva and Abilio 2004] [D'Almeida and Lobo 1998] [Ramanathan and Gulyani 2002].

Oxidative modification of lipids in brain clearly associates with impaired cognitive function [Carney and Starke-Reed 1991] [Forster and Dubey 1996]. Immobilization for a single eight-hour period increased brain lipid oxidation, which associated with decreased memory and behavior [Radak and Sasvari 2001], and lesser oxidation associated with improved cognitive function [Butterfield and Howard 1997] [Radak and Sasvari 2001]. Anti-oxidant nutrients blunt the increase in oxidized lipids when administered before or after immobilization stress [Zaidi and Al-Qirim 2003] [Zaidi and Al-Qirim 2005] [Radak and Sasvari 2001].

Isoprostane, a product of lipid oxidation, is elevated in autism [Ming and Stein 2005], and this elevation associates with other biochemical abnormalities [Yao and Walsh 2005]. As a biomarker for oxidative stress, isoprostane in urine is attractive for both research and clinical applications because it is stable for up to one week under refrigeration, or for several months at minus 10-degrees C. [Xue Ming, personal communication].

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