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Autism Studies and Related Medical Conditions, January 2009 - TACA

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chromatography linked t<strong>and</strong>em mass spectrometric (LC/MS/MS) method was<br />

used to determine the levels of SAA metabolites in peripheral blood mononuclear<br />

cells obtained from 11 healthy controls <strong>and</strong> 31 autistic children. Improved<br />

detection sensitivity <strong>and</strong> selectivity of the LC/MS/MS method allowed accurate<br />

quantification using small samples. Results show that leukocytes from autistic<br />

children contained significantly lower concentrations of S-adenosylmethionine (-<br />

35%; p = 0.01), <strong>and</strong> elevated levels of intracellular homocysteine content<br />

(+80%; p=0.003). Additionally, the levels of intracellular total cysteine <strong>and</strong><br />

glutathione (GSH) were reduced by 39% (p=0.004) <strong>and</strong> 25% (p=0.01),<br />

respectively. These autism-associated changes were leukocyte specific in that no<br />

significant alterations in SAA metabolite concentrations were detected in the<br />

plasma samples. Our results provide novel evidence for altered metabolism in<br />

immune cells; furthermore, this data suggest the involvement of inflammation in<br />

autism. Dietary differences between controls <strong>and</strong> patients, however, remain a<br />

potential confounder.<br />

Sweeten, T. L., D. J. Posey, et al. (2003). "High blood monocyte counts <strong>and</strong> neopterin<br />

levels in children with autistic disorder." Am J Psychiatry 160(9): 1691-3.<br />

OBJECTIVE: Leukocyte counts <strong>and</strong> plasma neopterin levels were determined in<br />

autistic children <strong>and</strong> matched healthy comparison subjects. METHOD: Blood from<br />

31 autistic children <strong>and</strong> 28 age- <strong>and</strong> gender-matched healthy comparison<br />

subjects was analyzed for numbers of neutrophils, eosinophils, basophils,<br />

lymphocytes, monocytes, <strong>and</strong> total leukocytes <strong>and</strong> for plasma neopterin levels.<br />

RESULTS: The monocyte count <strong>and</strong> neopterin level were significantly higher in<br />

the autistic children than in the comparison subjects. CONCLUSIONS: These<br />

results suggest that the immune system may be activated in some children with<br />

autism.<br />

Sweeten, T. L., D. J. Posey, et al. (2004). "High nitric oxide production in autistic<br />

disorder: a possible role for interferon-gamma." Biol Psychiatry 55(4): 434-7.<br />

BACKGROUND: Neuroimmune regulation abnormalities have been implicated in<br />

the pathophysiology of autistic disorder. Nitric oxide (NO) is involved in immune<br />

reactivity <strong>and</strong> is known to affect brain neurodevelopmental processes. Recent<br />

evidence indicates that NO, <strong>and</strong> cytokines involved in NO production, may be<br />

high in children with autism. The purpose of this study was to verify that plasma<br />

NO is high in children with autism <strong>and</strong> determine whether this elevation is<br />

related to plasma levels of cytokines involved in NO production. METHODS: The<br />

metabolites of NO, nitrite, <strong>and</strong> nitrate (NOx), along with the cytokines interferongamma<br />

(IFN-gamma), tumor necrosis factor-alpha, <strong>and</strong> interleukin-1beta, were<br />

measured in plasma of 29 children with autism (mean age +/- SD = 6.1 +/- 2.8<br />

years) <strong>and</strong> 27 age- <strong>and</strong> gender-matched healthy comparison subjects using<br />

commercially available assay kits. RESULTS: Plasma levels of NOx were<br />

significantly higher in the autistic subjects (p =.006); plasma levels of the<br />

cytokines did not differ between groups. NOx <strong>and</strong> IFN-gamma levels were<br />

<strong>Autism</strong> <strong>Studies</strong> & <strong>Related</strong> <strong>Medical</strong> <strong>Conditions</strong> – <strong>TACA</strong> © Page 100

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