Skip to main content

Brief Report: Plasma Leptin Levels are Elevated in Autism: Association with Early Onset Phenotype?

Abstract

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 (< .042), TD controls (< .0015), and DD controls (p < .004). We demonstrated an increase in leptin levels in autism, a finding driven by the early onset group.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  • 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.

    PubMed  Article  CAS  Google Scholar 

  • Banks, W. A. (2001). Leptin transport across the blood-brain barrier: Implications for the cause and treatment of obesity. Current Pharma Design, 7, 125–133.

    Article  CAS  Google Scholar 

  • Banks, W. A. (2004). The many lives of leptin. Peptides, 25, 331–338.

    PubMed  Article  CAS  Google Scholar 

  • Banks, W. A., & Lebel, C. R. (2002). Strategies for the delivery of leptin to the CNS. Journal of Drug Targeting, 10, 297–308.

    PubMed  Article  CAS  Google 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.

    CAS  Google Scholar 

  • Caldefie-Chezet, F., Poulin, A., & Vasson, M. P. (2003). Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radical Research, 37, 809–814.

    PubMed  Article  CAS  Google Scholar 

  • Chandra, R. K. (1980). Cell-mediated immunity in genetically obese C57BL/6J ob/ob) mice. American Journal of Clinical Nutrition, 33, 13–16.

    PubMed  CAS  Google Scholar 

  • DiLavore, P. C., Lord, C., & Rutter, M. (1995). The pre-linguistic autism diagnostic observation schedule. Journal of Autism and Develpmental Disorders, 25, 355–379.

    Article  CAS  Google Scholar 

  • Fantuzzi, G., Sennello, J. A., Batra, A., Fedke, I., Lehr, H. A., Zeitz, M., & Siegmund, B. (2005). Defining the role of T cell-derived leptin in the modulation of hepatic or intestinal inflammation in mice. Clinical and Experimental Immunology, 142, 31–38.

    PubMed  Article  CAS  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.

    PubMed  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  • Gupta, S., Aggarwal, S., Rashanravan, B., & Lee, T. (1998). Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. Journal of Neuroimmunology, 85, 106–109.

    PubMed  Article  CAS  Google Scholar 

  • Hammer, L. D., Kraemer, H. C., Wilson, D. M., Ritter, P. L., & Dornbusch, S. M. (1991). Standardized percentile curves of body-mass index for children and adolescents. American Journal of Diseases of Children, 145, 259–263.

    PubMed  CAS  Google Scholar 

  • Hertz-Picciotto, I., Croen, L. A., Hansen, R., Jones, C. R., Van de Water, J., & Pessah, I. N. (2006). The CHARGE study: An epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspectives, 114, 1119–1125.

    Article  Google 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.

    CAS  Article  Google Scholar 

  • Joseph, R. M., Tager-Flusberg, H., & Lord, C. (2002). Cognitive profiles and social-communicative functioning in children with autism spectrum disorder. Journal of Child Psychology and Psychiatry, 43, 807–821.

    PubMed  Article  Google Scholar 

  • Jyonouchi, H., Sun, S., & Itokazu, N. (2002). Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology, 46, 76–84.

    PubMed  Article  CAS  Google Scholar 

  • Kastin, A. J., Pan, W., Maness, L. M., & Banks, W. A. (1999). Peptides crossing the blood-brain barrier: Some unusual observations. Brain Research, 848, 96–100.

    PubMed  Article  CAS  Google Scholar 

  • Lainhart, J. E., Ozonoff, S., Coon, H., Krasny, L., Dinh, E., Nice, J., & McMahon, W. (2002). Autism, regression, and the broader autism phenotype. American Journal of Medical Genetics, 113, 231–237.

    PubMed  Article  Google Scholar 

  • Lord, C., Leventhal, B. L., & Cook, E. H. Jr. (2001). Quantifying the phenotype in autism spectrum disorders. American Journal of Medical Genetics, 105, 36–38.

    PubMed  Article  CAS  Google Scholar 

  • Lord, C., Pickles, A., McLennan, J., Rutter, M., Bregman, J., Folstein, S., Fombonne, E., Leboyer, M., & Minshew, N. (1997). Diagnosing autism: Analyses of data from the Autism Diagnostic Interview. Journal of Autism and Developmental Disorders, 27, 501–517.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    CAS  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.

    CAS  Google Scholar 

  • Matarese, G., Moschos, S., & Mantzoros, C. S., (2005). Leptin in immunology. Journal of Immunology, 174, 3137–3142.

    CAS  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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  • Pietrobelli, A., Faith, M. S., Allison, D. B., Gallagher, D., Chiumello, G., & Heymsfield, S. B. (1998). Body mass index as a measure of adiposity among children and adolescents: A validation study. Journal of Pediatrics, 132, 204–210.

    PubMed  Article  CAS  Google Scholar 

  • Plioplys, A. V., Greaves, A., & Yoshida, W. (1989). Anti-CNS antibodies in childhood neurologic diseases. Neuropediatrics, 20, 93–102.

    PubMed  CAS  Article  Google 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.

    PubMed  Article  Google Scholar 

  • Sanchez-Margalet, V., Martin-Romero, C., Santos-Alvarez, J., Goberna, R., Najib, S., & Gonzalez-Yanes, C. (2003). Role of leptin as an immunomodulator of blood mononuclear cells: Mechanisms of action. Clinical and Experimental Immunology. 133, 11–19.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  • Singh, V. K., & Rivas, W. H. (2004). Prevalence of serum antibodies to caudate nucleus in autistic children. Neuroscience Letters, 355, 53–56.

    PubMed  Article  CAS  Google Scholar 

  • Steinhausen, H. C., & Erdin, A. (1992). Abnormal psychosocial situations and ICD-10 diagnoses in children and adolescents attending a psychiatric service. Journal of Child Psychology and Psychiatry, 33, 731–740.

    PubMed  Article  CAS  Google Scholar 

  • Steinman, L., Conlon, P., Maki, R., & Foster, A. (2003). The intricate interplay among body weight, stress, and the immune response to friend or foe. Journal of Clinical Investigation, 111, 183–185.

    PubMed  Article  CAS  Google Scholar 

  • Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57, 67–81.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425–432.

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Judy Van de Water.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ashwood, P., Kwong, C., Hansen, R. et al. Brief Report: Plasma Leptin Levels are Elevated in Autism: Association with Early Onset Phenotype?. J Autism Dev Disord 38, 169–175 (2008). https://doi.org/10.1007/s10803-006-0353-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-006-0353-1

Keywords

  • Inflammation
  • Leptin
  • Autism
  • Regression