Brief Report: Plasma Leptin Levels are Elevated in Autism: Association with Early Onset Phenotype?
There is evidence of both immune dysregulation and autoimmune phenomena in children with autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without autism, and 23 children with developmental disabilities (DD). Children with autism had significantly higher plasma leptin levels compared with TD controls (p < .006). When further sub-classified into regression or early onset autism, children with early onset autism had significantly higher plasma leptin levels compared with children with regressive autism (p < .042), TD controls (p < .0015), and DD controls (p < .004). We demonstrated an increase in leptin levels in autism, a finding driven by the early onset group.
KeywordsInflammation Leptin Autism Regression
This study was supported by NIEHS 1 P01 ES11269-01, the US Environmental Protection Agency (US EPA) through the Science to Achieve Results (STAR) program (Grant R829388), the UC Davis M.I.N.D. Institute, The Ted Lindsay Foundation, and Visceral. We would like to thank the staff of both the UC Davis M.I.N.D Institute and the CHARGE study for their technical support. The commitment of the families who took part in these studies, at both the M.I.N.D Institute and as part of the CHARGE study, is also gratefully acknowledged.
- Ashwood, P., Anthony, A., Torrente, F., & Wakefield, A. J. (2004). Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: Mucosal immune activation and reduced counter regulatory interleukin-10. Journal of Clinical Immunology, 24, 664–673.PubMedCrossRefGoogle Scholar
- Busso, N., So, A., Chobaz-Peclat, V., Morard, C., Martinez-Soria, E., Talabot-Ayer, D., & Gabay, C. (2002). Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. Journal of Immunology, 168, 875–882.Google Scholar
- Filipek, P. A., Accardo, P. J., Ashwal, S., Baranek, G. T., Cook, E. H. Jr., Dawson, G., Gordon, B., Gravel, J. S., Johnson, C. P., Kallen, R. J., Levy, S. E., Minshew, N. J., Ozonoff, S., Prizant, B. M., Rapin, I., Rogers, S. J., Stone, W. L., Teplin, S. W., Tuchman, R. F., & Volkmar, F. R. (2000). Practice parameter: screening and diagnosis of autism: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology, 55, 468–479.PubMedGoogle Scholar
- Garcia-Mayor, R. V., Andrade, M. A., Rios, M., Lage, M., Dieguez, C., & Casanueva, F. F. (1997). Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. Journal of Clinical Endocrinology and Metabolism, 82, 2849–2855.PubMedCrossRefGoogle Scholar
- Howard, J. K., Lord, G. M., Matarese, G., Vendetti, S., Ghatei, M. A., Ritter, M. A., Lechler, R. I., & Bloom, S. R. (1999). Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. Journal of Clinical Investigations, 104, 1051–1059.CrossRefGoogle Scholar
- Lord, C., Risi, S., Lambrecht, L., Cook, E. H. Jr., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000). The autism diagnostic observation schedule-generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 205–223.PubMedCrossRefGoogle Scholar
- Mancuso, P., Gottschalk, A., Phare, S. M., Peters-Golden, M., Lukacs, N. W., & Huffnagle, G. B., (2002). Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. Journal of Immunology, 168, 4018–4024.Google Scholar
- Matarese, G., Di Giacomo, A., Sanna, V., Lord, G. M., Howard, J. K., Di Tuoro, A., Bloom, S. R., Lechler, R. I., Zappacosta, S., & Fontana, S. (2001). Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. Journal of Immunoogyl 166, 5909–5916.Google Scholar
- Matarese, G., Moschos, S., & Mantzoros, C. S., (2005). Leptin in immunology. Journal of Immunology, 174, 3137–3142.Google Scholar
- Owley, T., McMahon, W., Cook, E. H., Laulhere, T., South, M., Mays, L. Z., Shernoff, E. S., Lainhart, J., Modahl, C. B., Corsello, C., Ozonoff, S., Risi, S., Lord, C., Leventhal, B. L., & Filipek, P. A., (2001). Multisite, double-blind, placebo-controlled trial of porcine secretin in autism. Journal of the American Academy of Child and Adolescent Psychiatry, 40, 1293–1299.PubMedCrossRefGoogle Scholar
- Ozata, M., Ozdemir, I. C., & Licinio, J. (1999). Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. Journal of Clinical Endocrinology and Metabolism, 84, 3686–3695.PubMedCrossRefGoogle Scholar
- Richler, J., Luyster, R., Risi, S., Hsu, W.-L., Dawson, G., Bernier, R., Dunn, M., Hepburn, S., Hyman, S. L., McMahon, W. M., Goudie-Nice, J., Minshew, N., Rogers, S., Sigman, M., Spence, M. A., Goldberg. W. A., Tager-Flusberg, H., Volkmar, F. R., & Lord, C. (2006). Is there a ‘regressive phenotype’ of autism spectrum disorder associated with the measles-mumps-rubella vaccine? A CEA study. Journal of Autism and Developmental Disorders, 36, 299–316.PubMedCrossRefGoogle Scholar
- Sanna, V., Di Giacomo, A., La Cava, A., Lechler, R. I., Fontana, S., Zappacosta, S., & Matarese, G. (2003). Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. Journal of Clinical Investigation, 111, 241–250.PubMedCrossRefGoogle Scholar
- Vojdani, A., Campbell, A. W., Anyanwu, E., Kashanian, A., Bock, K., & Vojdani, E. (2002). Antibodies to neuron-specific antigens in children with autism: Possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. Journal of Neuroimmunology, 129, 168–177.PubMedCrossRefGoogle Scholar
- Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., & Chen, H. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation, 112, 1821–1830.PubMedCrossRefGoogle Scholar