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Elevation of Tumor Necrosis Factor-Alpha in Cerebrospinal Fluid of Autistic Children
Abstract
Recent reports implicating elevated cytokines in the central nervous system in a small number of patients studied with autism have reported clinical regression. These studies have not focused on tumor necrosis factor-alpha as a possible marker for inflammatory damage. A series of 10 children with autism had clinical evaluation of their serum and spinal fluid for inflammatory changes and possible metabolic disease as part of their neurological evaluation. Elevation of cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in all of the patients studied. The ratio of the cerebrospinal fluid levels to serum levels averaged 53.7:1. This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured. This observation may offer a unique insight into central nervous system inflammatory mechanisms that may contribute to the onset of autism and may serve as a potential clinical marker. More controlled study of this potentially important observation may prove valuable.
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“Moreover, increases in many cytokines and chemokines are observed in the brain and cerebrospinal fluid (CSF) of individuals with AD, in particular; interleukin (IL)-6, transforming growth factor beta 1 (TGFβ1), C-C motif ligand 2 (CCL2) and CCL17 in the cerebellum [73–76].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [74]
In the citing paper
“Furthermore, evidence suggests that children with ASD have elevated levels of pro-inflammatory cytokines including, interleukin 6 (IL–6), tumour necrosis factor alpha (TNF–α), and interferon gamma (IFN-γ) in different tissues [3,4,5,6,7].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [5]
In the citing paper
“Similarly, IFN-γ has been noted as increased in individuals with ASD,13, 16, 17, 61 and IFN-γ was increased in ASD and correlated with C disporicum and C tertium.”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [17]
In the citing paper
“Furthermore, increased IL6 has been seen in clinical cohorts of ASD.13, 14, 17, 60”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [17]
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“…reports suggest that a combination of environmental or perhaps in utero risk factors, autoimmune risk factors and localized inflammation of the central nervous system may contribute to the pathogenesis of ASD (Nelson et al., 2001; Vargas et al., 2005; Zimmerman et al., 2005; Chez et al., 2007).”
BackgroundImmune involvement in schizophrenia and autism: Etiology, pathology and animal models
Patterson, P. H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.12.016 · Cited by 766
“Most important is the recent evidence of dysregulation of immune-related genes in the schizophrenic brain, and striking microglial and astrocyte activation as well as cytokine up-regulation in the autistic brain and CSF [7] [8] [9] [10] [11] [12] [13].”
Consensus Paper: Pathological Role of the Cerebellum in Autism
Fatemi, S. H., Aldinger, K. A., Ashwood, P., Bauman, M. L., Blaha, C. D., Blatt, G. J., Chauhan, A., Chauhan, V., Dager, S. R., Dickson, P. E., et al. (2012) · The Cerebellum · doi:10.1007/s12311-012-0355-9 · Cited by 723
Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity
Olmos, G., & Lladó, J. (2014) · Mediators of Inflammation · doi:10.1155/2014/861231 · Cited by 730
“Interestingly, it has been proposed that an elevation of this ratio is a major cause of autism spectrum disorder [133, 134]; a pathology in that elevated levels of TNF-α in cerebrospinal fluid has been described [135].”
Maternal infection and immune involvement in autism
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“Recent results from studies of some of the same postmortem brains and new autism brain samples, as well as CSF, have supported these conclusions (6, 7).”
ResultBlood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders
Fiorentino, M., Sapone, A., Senger, S., Camhi, S. S., Kadzielski, S. M., Buie, T. M., Kelly, D. L., Cascella, N., & Fasano, A. (2016) · Molecular Autism · doi:10.1186/s13229-016-0110-z · Cited by 494
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Activation of the maternal immune system induces endocrine changes in the placenta via IL-6
Hsiao, E. Y., & Patterson, P. H. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.12.017 · Cited by 402
“IL-6 is also elevated in sera from living schizophrenic individuals (Maes et al., 2002; Potvin et al., 2008), and many pro-inflammatory cytokines are increased in the cerebrospinal fluid and sera from living autistic individuals (Ashwood et al., 2010; Chez et al., 2007; Pardo et al., 2006).”
BackgroundTargeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease
Decourt, B., Lahiri, D. K., & Sabbagh, M. N. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160930110551 · Cited by 383
Rossignol, D. A., & Frye, R. E. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00150 · Cited by 382
Garay, P. A., Hsiao, E. Y., Patterson, P. H., & McAllister, A. K. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.07.008 · Cited by 366
“It has been suggested that brain cytokines would be altered in MIA offspring based on observations of neural inflammation and cytokine changes in blood, CSF, and postmortem brain tissue from individuals with ASD and SZ (Ashwood et al., 2011a; Ashwood et al., 2011b; Ashwood et al., 2010; Chez et al., 2007; Molloy et al…”
Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation?
MEYER, U., FELDON, J., & DAMMANN, O. (2011) · Pediatric Research · doi:10.1203/pdr.0b013e318212c196 · Cited by 357
“For example, a nearly 50-fold increase in TNF- level was found in the cerebrospinal fluid (CSF) of autistic children (47), and severe inflammation is present in the brains of autistic patients from a broad range of ages (48), characterized by prominent activation of microglia and astroglia cells and enhanced proinflam…”
Understanding the Complexity of the Immune System during Pregnancy
Racicot, K. E., Kwon, J., Aldo, P. B., Silasi, M., & Mor, G. (2014) · American Journal of Reproductive Immunology · doi:10.1111/aji.12289 · Cited by 348
The association of maternal obesity and diabetes with autism and other developmental disabilities
Li, M., Fallin, M. D., Riley, A., Landa, R., Walker, S. O., Silverstein, M., Caruso, D., Pearson, C., Kiang, S., Dahm, J. L., et al. (2016) · PEDIATRICS · doi:10.1542/peds.2015-2206 · Cited by 338
Wei, H., Zou, H., Sheikh, A. M., Malik, M., Dobkin, C., Brown, W. T., & Li, X. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-52 · Cited by 333
ROS and Brain Diseases: The Good, the Bad, and the Ugly
Popa-Wagner, A., Mitran, S., Sivanesan, S., Chang, E., & Buga, A.-M. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/963520 · Cited by 427
“Similarly, in plasma F2dihomo-isoprostanes, a specific component of myelin in the brain of primates, plasma represents an early marker of Rett syndrome, a developmental disorder that almost exclusively affects females but has been found inmale patients, too [106].”
BackgroundLuna, R. A., Oezguen, N., Balderas, M., Venkatachalam, A., Runge, J. K., Versalovic, J., Veenstra-VanderWeele, J., Anderson, G. M., Savidge, T., & Williams, K. C. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.11.008 · Cited by 295
“A single study, with a follow-up report, remains the only characterization of the mucosal microbiome in pediatric ASD.23,34 Although focusing mainly on phylum level changes, the key differences associated with the ASD group with FGID were seen as an increase in Clostridiales, particularly in Lachnospiraceae and Rumino…”
BackgroundInfluentialAltered T cell responses in children with autism
Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I. N., & Van de Water, J. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.09.002 · Cited by 281
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“A number of recent studies have demonstrated that various inflammatory cytokines were elevated in blood mononuclear cells, serum, plasma and cerebrospinal fluid of autistic subjects [7-13].”
BackgroundPribiag, H., & Stellwagen, D. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0530-13.2013 · Cited by 260
“Deficits in GABAergic neurotransmission are also implicated in ASD (Chao et al., 2010; Han et al., 2012), which is often accompanied by immune dysregulation and elevated levels of TNF (Chez et al., 2007; Malik et al., 2011).”
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“The observations relating to elevated levels of PICs extend to TNF-α [107,108] and INF-γ, which are once again elevated in the brain [92] and the peripheral circulation, interestingly, correlated with the levels of other inflammatory mediators such as NO [109,110].”
BackgroundInflammation in Children and Adolescents With Neuropsychiatric Disorders: A Systematic Review
Mitchell, R. H. B., & Goldstein, B. I. (2013) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.11.013 · Cited by 247
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Kothur, K., Wienholt, L. A., Brilot, F., & Dale, R. C. (2015) · Cytokine · doi:10.1016/j.cyto.2015.10.001 · Cited by 240
Evidence for a Dysregulated Immune System in the Etiology of Psychiatric Disorders
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“(2007) detected elevated TNF-α in the cerebrospinal fluid of autistic children [4].”
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“In another study, TNFα was elevated in CSF from 10 autistic children with a history of regression (Chez et al., 2007).”
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“This has changed our view of ASD from a primary CNS disorder to a disorder that affects multiple physiological systems.”
InfluentialEvidence of microglial activation in autism and its possible role in brain underconnectivity
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“As mentioned earlier, there is evidence of proinflammatory cytokine profiles in the brain and cerebrospinal fluid of children with ASD (Vargas et al. , 2005; Zimmerman et al. , 2005; Chez et al. , 2007).”
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“Several studies have suggested an association between elevated levels of TNF- α and ASD: elevated levels of TNF- α in cerebrospinal fl uid (Chez et al. 2007), peripheral blood mononuclear cells (Jyonouchi et al. 2005, 2001), whole blood samples (Croonenberghs et al. 2002) and post mortem brain…”
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“A marked upregulation of tumor necrosis factor alpha (TNF-a) was observed in the CSF of autistic children (Chez et al., 2007), as were lowered D E V E L O P M E N T A L D Y N A M IC S immunoglobulin (IgG and IgM) plasma levels (Heuer et al., 2008), corroborating previous findings suggesting a…”
BackgroundResultKang, S. S., Kurti, A., Fair, D. A., & Fryer, J. D. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0156-9 · Cited by 167
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“Although it is not yet understood how CSF relates to the aetiology of ASD, it may be an early structural sign of improper fi ltering and draining of waste particles, potentially leading to neuro-in fl ammation and autism (Chez et al., 2007; Zimmerman et al., 2005).”
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“A number of papers have reported increased brain expression or cerebrospinal fluid (CSF) levels of pro-inflammatory cytokines, especially TNF, which is preformed in mast cells.”
InfluentialNutritional interventions for autism spectrum disorder
Karhu, E., Zukerman, R. J., Eshraghi, R. S., Mittal, J., Deth, R. C., Castejon, A. M., Trivedi, M. S., Mittal, R., & Eshraghi, A. A. (2019) · Nutrition Reviews · doi:10.1093/nutrit/nuz092 · Cited by 159
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“…immunological factors also appear to be involved, in that chronically increased levels of IL-1β, IL6, IL-8 and TNF-α are positively associated with the severity of the schizophrenia or autism that eventually develops (Maes et al., 2002; Chez et al., 2007; Potvin et al., 2008; Ashwood et al., 2011).”
BackgroundThe relationship between mercury and autism: A comprehensive review and discussion
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Wei, H., Alberts, I. L., & Li, X. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.08.025 · Cited by 139
“Chez et al. has also reported the elevation of tumor necrosis factor (TNF)-a in the cerebrospinal fluid of autistic subjects (Chez et al., 2007).”
BackgroundMast cell activation and autism
Theoharides, T. C., Angelidou, A., Alysandratos, K.-D., Zhang, B., Asadi, S., Francis, K., Toniato, E., & Kalogeromitros, D. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.017 · Cited by 125
“Biochimica et Biophysica Acta xxx (2011) xxx–xxx BBADIS-63219; No. of pages: 8; 4C: 3, 4, 5, 6 Contents lists available at ScienceDirect Biochimica et Biophysica Acta j ourna l homepage: www.e lsev ie r.com/ locate /bbad is Review Mast cell activation and autism☆ Theoharis C. Theoharides a,b,c,d,e,⁎, Asimenia Angelido…”
BackgroundInfluentialImmune Abnormalities in Autism Spectrum Disorder—Could They Hold Promise for Causative Treatment?
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“Only three studies [213, 227, 232] focused on both CSF and peripheral blood and did not confirm any correlation between the same proteins in those two samples.”
BackgroundRecent Updates in the Treatment of Neurodegenerative Disorders Using Natural Compounds
Rasool, M., Malik, A., Qureshi, M. S., Manan, A., Pushparaj, P. N., Asif, M., Qazi, M. H., Qazi, A. M., Kamal, M. A., Gan, S. H., et al. (2014) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2014/979730 · Cited by 124
“Multiple biochemical andmolecular features could be observed for the neurodegeneration in the brain of ASD [35, 36] including oxidative stress [37, 38], activated astrocytes and microglia [39, 40], neuronal loss [35, 40], elevated levels of 8-oxo-guanosine [41], and development of proinflammatory cytokines [40, 42].”
BackgroundBiomarkers in autism spectrum disorders: Current progress
Shen, L., Liu, X., Zhang, H., Lin, J., Feng, C., & Iqbal, J. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.12.009 · Cited by 132
A Case Series of a Luteolin Formulation (Neuroprotek®) in Children with Autism Spectrum Disorders
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“CSF levels ofTNF were significantly increased in autistic children (17), while brains ofASD patients had elevated expression of IL-6 (18).”
BackgroundEhninger, D., Sano, Y., de Vries, P. J., Dies, K., Franz, D., Geschwind, D. H., Kaur, M., Lee, Y.-S., Li, W., Lowe, J. K., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2010.115 · Cited by 120
Cattane, N., Richetto, J., & Cattaneo, A. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.07.001 · Cited by 129
The Neurobiology of Lipid Metabolism in Autism Spectrum Disorders
Tamiji, J., & Crawford, D. A. (2010) · Neurosignals · doi:10.1159/000323189 · Cited by 116
Vitamin D and Autism Spectrum Disorder: A Literature Review
Mazahery, H., Camargo, C., Conlon, C., Beck, K., Kruger, M., & Von Hurst, P. (2016) · Nutrients · doi:10.3390/nu8040236 · Cited by 110
“Furthermore, evidence suggests that children with ASD have elevated levels of pro-inflammatory cytokines including, interleukin 6 (IL–6), tumour necrosis factor alpha (TNF–α), and interferon gamma (IFN-γ) in different tissues [3–7].”
BackgroundRelevance of Neuroinflammation and Encephalitis in Autism
Kern, J. K., Geier, D. A., Sykes, L. K., & Geier, M. R. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00519 · Cited by 117
“…suggestive of ongoing neuroinflammation or encephalitis (encephalitis is defined as brain inflammation) in different regions of the brain (Enstrom et al., 2005; Pardo et al., 2005; Vargas et al., 2005; Zimmerman et al., 2005; Chez et al., 2007; Morgan et al., 2010, 2012; Tetreault et al., 2012).”
BackgroundResultInfluentialGustafsson, H., Sullivan, E. L., Nousen, E. K., Sullivan, C. A., Huang, E., Rincon, M. P., Nigg, J. T., & Loftis, J. M. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.06.011 · Cited by 118
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“…both disorders; inflammation is present in postmortem brains, and cytokine levels are altered in the blood, brain, and cerebrospinal fluid in ASD and SZ (Vargas et al., 2005; Chez et al., 2007; Patterson, 2009; Morgan et al., 2010; Watanabe et al., 2010; Ashwood et al., 2011; Wei et al., 2011).”
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The neurobiology of autism spectrum disorders
Parellada, M., Penzol, M. J., Pina‐Camacho, L., Moreno, C., González‐Vioque, E., Zalsman, G., & Arango, C. (2013) · European Psychiatry · doi:10.1016/j.eurpsy.2013.02.005 · Cited by 115
“shown to be increased in the cerebral spinal fluid (CSF) of autistic patients [121,20].”
BackgroundEvidence of parallels between mercury intoxication and the brain pathology in autism
Kern, J. K., Geier, D. A., AUDHYA, T. K., King, P. G., Sykes, L. K., & Geier, M. R. (2012) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2012-1887 · Cited by 103
Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders
Bhandari, R., & Kuhad, A. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.12.012 · Cited by 103
Pendyala, G., Chou, S., Jung, Y., Coiro, P., Spartz, E., Padmashri, R., Li, M., & Dunaevsky, A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.7 · Cited by 97
“…in biofluids such as blood, cerebrospinal fluid as well as the brain in ASD patients suggesting a neuroinflammatory condition to contribute to the symptoms and pathology of ASD (Ashwood et al, 2011a; Ashwood et al, 2011b; Chez et al, 2007; Molloy et al, 2006; Pardo et al, 2005; Vargas et al, 2005).”
BackgroundRossignol, D. A., Rossignol, L. W., Smith, S. A., Schneider, C., Logerquist, S., Usman, A., Neubrander, J., Madren, E. M., Hintz, G., Grushkin, B., et al. (2009) · BMC Pediatrics · doi:10.1186/1471-2431-9-21 · Cited by 97
“Multiple studies have reported that these problems are relatively common in children with autism [26-34].”
Saresella, M., Marventano, I., Guerini, F. R., Mancuso, R., Ceresa, L., Zanzottera, M., Rusconi, B., Maggioni, E., Tinelli, C., & Clerici, M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.06.020 · Cited by 101
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Baj, J., Flieger, W., Flieger, M., Forma, A., Sitarz, R., Skórzyńska-Dziduszko, K., Grochowski, C., Maciejewski, R., & Karakuła‐Juchnowicz, H. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.029 · Cited by 100
“Numerous studies confirm increased neuroinflammatory reactivity and neuronal damage in the brain of ASD patients (Chez et al., 2007; Enstrom et al., 2005; Fatemi et al., 2008; Laurence and Fatemi, 2005; Morgan et al., 2012, 2010; Pardo et al., 2005; Tetreault et al., 2012; Vargas et al., 2005;…”
BackgroundEissa, N., Sadeq, A. S., Sasse, A., & Sadek, B. S. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00886 · Cited by 99
Tartaglione, A. M., Villani, A., Ajmone‐Cat, M. A., Minghetti, L., Ricceri, L., Pazienza, V., Simone, R. D., & Calamandrei, G. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02149-9 · Cited by 98
Evidence of neurodegeneration in autism spectrum disorder
Kern, J. K., Geier, D. A., Sykes, L. K., & Geier, M. R. (2013) · Translational Neurodegeneration · doi:10.1186/2047-9158-2-17 · Cited by 95
“Chez et al [46] also observed that there was a significant increase in TNF-α in the CSF of individuals diagnosed was an ASD in comparison to the concurrent serum levels and that the magnitude of the difference was significantly higher than that observed for other diseases.”
ResultNg, M., de Montigny, J., Ofner, M., & Do, M. (2017) · Health Promotion and Chronic Disease Prevention in Canada · doi:10.24095/hpcdp.37.1.01 · Cited by 94
Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism
Costa, L. G., Chang, Y. C., & Cole, T. B. (2017) · Current Environmental Health Reports · doi:10.1007/s40572-017-0135-2 · Cited by 94
A Study of Nuclear Transcription Factor-Kappa B in Childhood Autism
Naik, U., Gangadharan, C., Abbagani, K., Balakrishna, N., Dasari, N., & Manna, S. K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019488 · Cited by 88
Bhandari, R., & Kuhad, A. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.09.012 · Cited by 85
Cytokine profile in autistic patients
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Novel therapeutic targets for autism
Theoharides, T. C., Doyle, R., Francis, K., Conti, P., & Kalogeromitros, D. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.06.002 · Cited by 81
Autism: an emerging ‘neuroimmune disorder’ in search of therapy
Theoharides, T. C., Kempuraj, D., & Redwood, L. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560903107789 · Cited by 79
“Cerebrospinal fluid (CSF) levels of tumor necrosis factor (TNF) were significantly higher than corresponding serum levels in ten autistic children [50] .”
BackgroundAutism Spectrum Disorders and Mastocytosis
Theoharides, T. C. (2009) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200902200401 · Cited by 79
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A review of recent reports on autism: 1000 studies published in 2007
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“[96] showed an elevation of cerebral spinal fluid tumor necro-”
BackgroundAssociation between Viral Infections and Risk of Autistic Disorder: An Overview
Shuid, A. N., Jayusman, P. A., Shuid, N., Ismail, J., Nor, N. K., & Mohamed, I. N. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18062817 · Cited by 82
Cieślik, M., Gąssowska-Dobrowolska, M., Jęśko, H. M., Czapski, G. A., Wilkaniec, A., Zawadzka, A., Dominiak, A., Polowy, R., Filipkowski, R. K., Boguszewski, P. M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114097 · Cited by 77
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Neurotensin is increased in serum of young children with autistic disorder
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“Another study reported that TNF-a levels in CSF of patients with ASD (n = 10) were significantly higher than concurrent serum levels [40].”
BackgroundMicroglia Ontology and Signaling
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“However, recent lessons from macrophages suggested that the same cell has the potential to adopt M1 or M2 phenotype based on either the nature of the stimuli and/or on the original activation status of the cell before being exposed to the stimuli (Mosser and Edwards, 2008).”
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“Moreover, levels of inflammation-associated cytokines such as tumor necrosis factor-alpha (TNF-a) are significantly elevated in CSF and postmortem brain samples from autistic subjects [30,31,54], which suggests that cortical MS status might be altered by oxidative stress in autism.”
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Self-citation
Metadata
- Authors
- Chez, M. G., Dowling, T., Patel, P. B., Khanna, P., & Kominsky, M.
- Affiliations
- Sutter Health (US)
- Illinois State University (US)
- Rosalind Franklin University of Medicine and Science (US)
- Corresponding author
- Chez, Michael G.
- ORCID
- Chez, Michael G.
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 36
- Issue
- 6
- Pages
- 361-365
- ISSN
- 0887-8994 (ISSN-L)
- OpenAlex
- W2063547860
- Cited by
- 317
- References
- 16
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 20 · 2023: 10 · 2022: 21 · 2021: 22 · 2020: 19 · 2019: 16 · 2018: 24 · 2017: 15 · 2016: 21 · 2015: 17 · 2014: 15 · 2013: 21 · 2012: 18
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TNF-α, cerebrospinal fluid, autism spectrum disorder, cytokines, neuroinflammation, biomarkers
- MeSH terms
- Autistic Disorder, Central Nervous System, Child, Child, Preschool, Encephalitis, Female, Humans, Infant, Male, Tumor Necrosis Factor-alpha, Biomarkers, Early Diagnosis
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