Cerebrospinal Fluid and Serum Markers of Inflammation in Autism

Zimmerman, Andrew W.; Jyonouchi, Harumi; Comi, Anne M.; Connors, Susan L.; Milstien, Sheldon; Varsou, Angeliki; Heyes, Melvyn P.

doi:10.1016/j.pediatrneurol.2005.03.014

« Previous Next »Pediatric Neurology
Volume 33, Issue 3 , Pages 195-201, September 2005

Cerebrospinal Fluid and Serum Markers of Inflammation in Autism

Andrew W. Zimmerman, MD
- Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore Maryland
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Communications should be addressed to: Dr. Zimmerman; Dept. of Neurology and Developmental Medicine; Kennedy Krieger Institute; 707 North Broadway; Baltimore, MD 21205.
Harumi Jyonouchi, MD
- Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey
Anne M. Comi, MD
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Susan L. Connors, MD
- Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore Maryland
Sheldon Milstien, PhD
- National Institutes of Mental Health, Bethesda, Maryland
Angeliki Varsou, PhD
- University of Athens School of Medicine, Athens, Greece
Melvyn P. Heyes, PhD
- National Institutes of Mental Health, Bethesda, Maryland
- PsychoGenics, Inc., Hawthorne, New York

Received 18 January 2005; accepted 28 March 2005.

Systemic immune abnormalities have no known relevance to brain dysfunction in autism. In order to find evidence for neuroinflammation, we compared levels of sensitive indicators of immune activation: quinolinic acid, neopterin, and biopterin, as well as multiple cytokines and cytokine receptors, in cerebrospinal fluid and serum from children with autism, to control subjects with other neurologic disorders. In cerebrospinal fluid from 12 children with autism, quinolinic acid (P = 0.037) and neopterin (P = 0.003) were decreased, and biopterin (P = 0.040) was elevated, compared with control subjects. In sera from 35 persons with autism, among cytokines, only tumor necrosis factor receptor II was elevated compared with controls (P < 0.02). Decreased quinolinic acid and neopterin in cerebrospinal fluid are paradoxical and suggest dysmaturation of metabolic pathways and absence of concurrent infection, respectively, in autism. Alternatively, they may be produced by microglia but remain localized and not expressed in cerebrospinal fluid.