APA. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. Washington, DC: American Psychiatric Association, 2013.
Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry 2008, 47: 921–929.
Mannion A, Leader G. An investigation of comorbid psychological disorders, sleep problems, gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder: A two year follow-up. Res Autism Spectr Disord 2016, 22: 20–33.
Mannion A, Leader G. Comorbidity in autism spectrum disorder: A literature review. Res Autism Spectr Disord 2013b, 7: 1595–1616.
Bauman ML. Medical comorbidities in autism: Challenges to diagnosis and treatment. Neurotherapeutics 2010, 7: 320–327.
Zerbo O, Leong A, Barcellos L, Bernal P, Fireman B, Croen LA. Immune mediated conditions in autism spectrum disorders. Brain Behav Immun 2015, 46: 232–236.
Goines P, Van de Water J. The immune system’s role in the biology of autism. Curr Opin Neurol 2010, 23: 111–117.
Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ. Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 2015, 20: 440–446.
Mead J, Ashwood P. Evidence supporting an altered immune response in ASD. Immunol Lett 2015, 163: 49–55.
Owen JA, Punt J, Stranford SA, Jones PP, Kuby J. Kuby Immunology. New York: W.H. Freeman, 2013.
D’Elia RV, Harrison K, Oyston PC, Lukaszewski RA, Clark GC. Targeting the “cytokine storm” for therapeutic benefit. Clin Vaccine Immunol 2013, 20: 319–327.
Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? the example of natural killer cells. Science 2011, 331: 44–49.
Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2014, 1843: 2563–2582.
Graves DT, Jiang Y. Chemokines, a family of chemotactic cytokines. Crit Rev Oral Biol Med 1995, 6: 109–118.
Depino MA, de los Angeles Robinson-Agramonte M. Understanding on neuroimmunology in autism spectrum disorder. Translational approaches to autism spectrum disorder. Springer International Publishing, 2015: 155–180.
Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol 2010, 28: 445–489.
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell. 4th edition. New York: Garland Science; 2002. Helper T Cells and Lymphocyte Activation.
Gupta S, Aggarwal S, Rashanravan B, Lee T. Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. J Neuroimmunol 1998, 85: 106–109.
Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, et al. Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol 2006, 172: 198–205.
Romagnani S. T-cell subsets (Th1 versus Th2). Ann Allergy Asthma Immunol 2000, 85: 9–21.
Shi Y, Liu CH, Roberts AI, Das J, Xu G, Ren G, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don’t know. Cell Res 2006, 16: 126–133.
Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 2004, 75: 163–189.
Xu N, Li X, Zhong Y. Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediators Inflamm 2015, 2015: 10.
Cavaillon JM. Pro- versus anti-inflammatory cytokines: Myth or reality. Cell Mol Biol (Noisy-le-grand) 2001, 47: 695–702.
Filiano AJ, Gadani SP, Kipnis J. Interactions of innate and adaptive immunity in brain development and function. Brain Res 2015, 1617: 18–27.
Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 1988, 12: 123–137.
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008, 9: 46–56.
Dantzer R. Cytokine, sickness behavior, and depression. Immunol. Allergy Clin North Am 2009, 29: 247–264.
Dantzer R. Cytokine-Induced Sickness Behavior: Where Do We Stand? Brain Behav Immun 2001, 15: 7–24.
Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacology & therapeutics 2011, 130: 226–238.
Denicoff KD, Rubinow DR, Papa MZ, Simpson C, Seipp CA, Lotze MT, et al. The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 1987, 107: 293–300.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010, 67: 446–457.
Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011, 70: 663–671.
Modabbernia A, Taslimi S, Brietzke E, Ashrafi M. Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol Psychiatry 2013, 74: 15–25.
Capuron L, Castanon N. Role of inflammation in the development of neuropsychiatric symptom domains: evidence and mechanisms. Curr Top Behav Neurosci 2017, 31: 31–44.
Mitchell RH, Goldstein BI. Inflammation in children and adolescents with neuropsychiatric disorders: a systematic review. J Am Acad Child Adolesc Psychiatry 2014, 53: 274–296.
Tilleux S, Hermans E. Neuroinflammation and regulation of glial glutamate uptake in neurological disorders. J Neurosci Res 2007, 85: 2059–2070.
Rubenstein JL, Merzenich MM. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav 2003, 2: 255–267.
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015, 523: 337–341.
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Altered T cell responses in children with autism. Brain Behav Immun 2011, 25: 840–849.
Filiano AJ, Xu Y, Tustison NJ, Marsh RL, Baker W, Smirnov I, et al. Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. Nature 2016, 535: 425–429.
Forbes CE, Grafman J. The role of the human prefrontal cortex in social cognition and moral judgment. Annu Rev Neurosci 2010, 33: 299–324.
Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen R, Pessah IN, et al. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun 2009, 23: 124–133.
Stubbs EG, Crawford ML. Depressed lymphocyte responsiveness in autistic children. J Autism Child Schizophr 1977, 7: 49–55.
Meltzer A, Van de Water J. The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 2017, 42: 284–298.
Atladottir HO, Thorsen P, Ostergaard L, Schendel DE, Lemcke S, Abdallah M, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord 2010, 40: 1423–1430.
Jiang HY, Xu LL, Shao L, Xia RM, Yu ZH, Ling ZX, et al. Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis. Brain Behav Immun 2016, 58: 165–172..
Estes ML, McAllister AK. Maternal immune activation: Implications for neuropsychiatric disorders. Science 2016, 353: 772–777.
Krakowiak P, Goines PE, Tancredi DJ, Ashwood P, Hansen RL, Hertz-Picciotto I, et al. Neonatal cytokine profiles associated with autism spectrum disorder. Biol Psychiatry 2017, 81: 442–451..
Atladottir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 2009, 124: 687–694.
Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S. Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One 2011, 6: e20470.
Netea MG, Simon A, van de Veerdonk F, Kullberg B-J, Van der Meer JWM, Joosten LAB. IL-1β Processing in Host Defense: Beyond the Inflammasomes. PLoS Pathog 2010, 6: e1000661.
Li L, Kim J, Boussiotis VA. IL-1beta-mediated signals preferentially drive conversion of regulatory T cells but not conventional T cells into IL-17-producing cells. J Immunol 2010, 185: 4148–4153.
Verma ND, Hall BM, Plain KM, Robinson CM, Boyd R, Tran GT, et al. Interleukin-12 (IL-12p70) Promotes Induction of Highly Potent Th1-Like CD4(+)CD25(+) T Regulatory Cells That Inhibit Allograft Rejection in Unmodified Recipients. Front Immunol 2014, 5: 190.
Ricci S, Businaro R, Ippoliti F, Lo Vasco VR, Massoni F, Onofri E, et al. Altered cytokine and BDNF levels in autism spectrum disorder. Neurotox Res 2013, 24: 491–501.
Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M. Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 2007, 36: 361–365.
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011, 1813: 878–888.
Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M. Activation of the inflammatory response system in autism. Neuropsychobiology 2002, 45: 1–6.
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005, 57: 67–81.
Li X, Chauhn A, Shiekh AM, Patil S, Chauhn V, Li X-M, et al. Elevated immune response in the brain of autistic patients. J Neuroimmunol 2009, 207: 111–116.
Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, et al. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation 2011, 8: 52.
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 2011a, 25: 40–45.
Wei H, Chadman KK, McCloskey DP, Sheikh AM, Malik M, Brown WT, et al. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta 2012, 1822: 831–842.
Miano S, Giannotti F, Cortesi F. Sleep disorders and autism spectrum disorder. In: Mazzone L, Vitiello B (Eds.). Psychiatric symptoms and comorbidities in autism spectrum disorder. Springer International Publishing, 2016: 111–128.
Rohleder N, Aringer M, Boentert M. Role of interleukin-6 in stress, sleep, and fatigue. Ann N Y Acad Sci 2012, 1261: 88–96.
McDougle CJ, Landino SM, Vahabzadeh A, O’Rourke J, Zurcher NR, Finger BC, et al. Toward an immune-mediated subtype of autism spectrum disorder. Brain Res 2015, 1617: 72–92.
Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA, et al. Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol 2008, 204: 149–153.
El Gohary TM, El Aziz NA, Darweesh M, Sadaa ES. Plasma level of transforming growth factor β 1 in children with autism spectrum disorder. Egyptian Journal of Ear, Nose, Throat and Allied Sciences 2015, 16: 69–73.
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 2011b, 232: 196–199.
Biber K, Vinet J, Boddeke HWGM. Neuron-microglia signaling: Chemokines as versatile messengers. J Neuroimmunol 2008, 198: 69–74.
Goines PE, Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicol Teratol 2013, 36: 67–81.
Courchesne E. Brain development in autism: Early overgrowth followed by premature arrest of growth. Ment Retard Dev Disabil Res Rev 2004, 10: 106–111.
Bickel M. The role of interleukin-8 in inflammation and mechanisms of regulation. J Periodontol 1993, 64: 456–460.
Qazi BS, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. Int J Inflam 2011, 2011: 908468.
Ashwood P, Corbett BA, Kantor A, Schulman H, Van de Water J, Amaral DG. In search of cellular immunophenotypes in the blood of children with autism. PLoS One 2011c, 6: e19299.
Enstrom A, Krakowiak P, Onore C, Pessah IN, Hertz-Picciotto I, Hansen RL, et al. Increased IgG4 levels in children with autism disorder. Brain Behav Immun 2009, 23: 389–395.
Heuer L, Ashwood P, Schauer J, Goines P, Krakowiak P, Hertz-Picciotto I, et al. Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Res 2008, 1: 275–283.
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 2001, 69: 89–95.
Banati R, Hickie IB. Therapeutic signposts: using biomarkers to guide better treatment of schizophrenia and other psychotic disorders. Med J Aust 2009, 190: S26.
Ruggeri B, Sarkans U, Schumann G, Persico A. Biomarkers in autism spectrum disorder: the old and the new. Psychopharmacology (Berl.) 2014, 231: 1201–1216.
Akhondzadeh S, Fallah J, Mohammadi MR, Imani R, Mohammadi M, Salehi B, et al. Double-blind placebo-controlled trial of pentoxifylline added to risperidone: effects on aberrant behavior in children with autism. Prog. Neuropsychopharmacol. Biol Psychiatry 2010, 34: 32–36.
Ghaleiha A, Rasa SM, Nikoo M, Farokhnia M, Mohammadi M-R, Akhondzadeh S. A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism. Psychiatry Res 2015, 229: 181–187.
Kobayashi T, Notoya K, Naito T, Unno S, Nakamura A, Martel-Pelletier J, et al. Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, reduces the progression of experimental osteoarthritis in guinea pigs. Arthritis Rheum 2005, 52: 479–487.
Mandrekar-Colucci S, Karlo JC, Landreth GE. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. J Neurosci 2012, 32: 10117–10128.
Asadabadi M, Mohammadi MR, Ghanizadeh A, Modabbernia A, Ashrafi M, Hassanzadeh E, et al. Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl.) 2013, 225: 51–59.
Choi JE, Widjaja F, Careaga M, Bent S, Ashwood P, Hendren RL. Change in plasma cytokine levels during risperidone treatment in children with autism. J Child Adolesc Psychopharmacol 2014, 24: 586–589.
Hayashi-Takagi A, Vawter MP, Iwamoto K. Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research. Biol Psychiatry 2014, 75: 920–928.
Insel TR. The NIMH research domain criteria (RDoC) project: precision medicine for psychiatry. Am J Psychiatry 2014, 171: 395–397.
National Academy of Sciences. The national academies collection: reports funded by national institutes of health. Washington (DC): National Academies Press (US), 2011.
Kitano H. Biological robustness. Nat Rev Genet 2004, 5: 826–837.
Derecki N, Privman E, Kipnis J. Rett syndrome and other autism spectrum disorders—brain diseases of immune malfunction? Mol Psychiatry 2010, 15: 355–363.