The Diagnostic Value of Neutrophil-Lymphocyte Ratio in Diagnosis of Autism Spectrum Disorders

Nurmalia Purnama Sari, Yudianita K., M. Rafli Haiqal, M. Fadill Akbar


Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder, progressive disruption of brain development and synaptic connections, which causes impaired communication and behavioral disorders. However, the etiology is unknown. A damaged perinatal environment causes chronic nerve inflammation in genetically susceptible children of ASD, dysregulation of the immune system, which leads to ASD. The ratio of Neutrophil to Lymphocyte (NLR) as one of the markers of inflammation is frequently associated with inflammation-related psychiatric diseases and is potentially used as a diagnostic instrument. A cross-sectional study was carried out from June to November 2019 by using medical records of Outpatients with growth and development disorders and ASD and involving 69 children. The diagnosis of ASD was confirmed by the fifth edition Diagnostic and Manual of Mental Disorders criteria (DSM-V). A routine hematology test was carried out with a flow cytometry method. Diagnostic tests were performed in 43 children with developmental disorders (mean NLR 1.01±0.07) and 26 ASD children (mean NLR 1.02±0.06), with a cut-off value of 0.68. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of NLR were 84.62%; 27.9%; 41.51%; 25%; and 50.2%, respectively. Neutrophil to lymphocyte is sensitive to diagnose ASD but its accuracy is low. Immune dysfunction and complex neurodevelopmental disorders that are affected by chronic inflammation play a role in the occurrence of ASD. Other inflammatory markers are needed to improve the accuracy of laboratory tests to diagnose ASD.


Autism spectrum disorders, neutrophil to lymphocyte ratio, DSM-V

Full Text:



Boat TF, Wu JT. Mental disorders and disabilities among low-income children. The 1st Ed., United States of America, The National Academies Press, 2015; 157-165.

Hari peduli autisme sedunia:Kenali gejalanya, pahami keadaannya. 2018 (accessed Des 7, 2019). Available at:

Taylor B, Jick H, MacLaughlin D. Prevalence and incidence rates of autism in the UK: Time trend from 2004–2010 in children aged 8 years. BMJ, 2013; 1-6.

Arlington VA. American psychiatric association. 5th Ed., Autism spectrum disorders, in diagnostic and statistical manual of mental disorders. Washington DC, American Psychiatric Publishing, 2013; 50-59.

Adam MHY, Bhismadev C, David R, Meng C, John S, Simon BC. From molecules to neural morphology: Understanding neuroinflammation in autism spectrum condition. Moleculer autism. Biomed Central, 2016; 7(9): 1-8.

DA Rossignol, RE Frye. A review of research trends in physiological abnormalities in autism spectrum disorders: Immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Molecular Psychiatry, 2012; 17: 389–401.

Alvina Putri PS, Mohamad A, Betty L. Causes of autism disorders through the neuroinflammation pathway. Bio-experiment penyebab gangguan autis melalui jalur neuroinflamasi. Bioeksperimen, 2017; 3(2): 1-9.

Ningan X, Xiaohong Li, Yan Zhong. Inflammatory cytokines: Potential biomarkers of immunologic dysfunction in autism spectrum disorders. Hindawi Publishing Corporation, 2015; 1-10.

Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, PessahI, 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. 2011; 25: 40–45.

Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, et al. Elevated cytokine levels in children with an autism spectrum disorder. J. Neuroimmunol, 2006; 172: 98–205.

Inga Jácome MC, Morales C, Vera Cuesta H, Maragoto RC, Whilby SM, et al. Peripheral inflammatory markers contributing to comorbidities in autism. Behav. Sci, 2016; 6: 1-29.

Dario S, Stephen S, Anna LB, Nicola A. Review inflammation and neuro-immune dysregulations in autism spectrum disorders. Pharmaceuticals, 2018; 11(56): 1-14.

Brigida AL, Schultz S, Cascone M, Antonucci N, Siniscalco D. Endocannabinoid signal dysregulation in autism spectrum disorders: A Correlation link between inflammatory state and neuro-immune alterations. Int. J. Mol. Sci, 2017; 18: 1-13.

Siniscalco D, Bradstreet JJ, Cirillo A, Antonucci N. The in-vitro GcMAF effects on endocannabinoid system transcriptomics, receptor formation, and cell activity of autism-derived macrophages. J. Neuroinflamm, 2014; 11: 1-8.

Gehan AM, Laila YA. The possible link between elevated serum levels of epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic children. Behavioral and brain function. Bio Med Central. 2015; 11(11): 1-7.

Ashwood P, Corbett BA, Kantor A, Schulman H, de Water JV, Amaral DG. In search of cellular immunophenotypes in the blood of children with autism. PLos One. 2011; 6(5): e19299: 1-9.

Özdin S, Böke Ö. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in different stages of schizophrenia. Psychiatry Research, Elsevier, 2019; 11: 131-5.

Mazza MG, Tringali AGM, Rossetti A, Botti RE, Clerici M. Cross-sectional study of neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in mood disorders. General Hospital Psychiatry, Elsevier, 2019; 58: 7–12.

Zekiye C, Emel U, Nefise O, Kader U. Comparison of neutrophil-to-lymphocyte, platelet-to lymphocyte, and monocyte-to-lymphocyte ratios in patients with schizophrenia, bipolar disorder, and major depressive disorder. Int J Med Biochem, 2018; 1(3): 106-10.

Tural HS, KasakM, Cıtak AN, Ceylan MF. High monocyte level and low lymphocyte to monocyte ratio in autism spectrum disorders. International Journal of Developmental Disabilities, 2017; 65(2): 73–81.

Jennifer HE, Consuelo MK, Susan NB, Margaret A. Clinical impact of early diagnosis of autism on the prognosis and parent-child relationships. Psychology Research and Behavior Management, 2017;10 : 283–92

SA Nugraheni. Menguak belantara autisme. Buletin Psikologi. Fakultas Psikologi Universitas Gadjah Mada, 2012; 20(1-2): 9–17.

Kutlu A, Cevher BN. Does increased neutrophil-lymphocyte ratio predict autism spectrum disorder?. Anadolu Psikiyatri Derg, 2018; 19(6): 607-14.

Kleinman JM, Robins DL, Ventola PE, Pandey J, Boorstein HC, et al. The modified checklist for autism in toddlers: A follow-up study investigating the early detection of autism spectrum disorders. Journal of Autism and Developmental Disorders, 2008; 38(5): 827–39.

Parker W, Hornik CD, Bilbo S, Holzknecht ZE, Gentry L, Rao R Nevison CD. The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism. Journal of International Medical Research, 2017; 45(2):407–38.

Sibel K, Cem K. High neutrophil to lymphocyte ratio and low mean platelet volume level in autism spectrum disorders. Annals of Medical Research, 2019; 26(10): 2382-5.

Şahin, N. Evaluation of neutrophil/ lymphocyte ratio in children with autism and the relationship between autism severities. Psychiatry and Clinical Psychopharmacology, 2018; 28: 23-38.

Dahlan, Sopiyudin M. Besar sampel dan cara pengambilan sampel. Jakarta, Salemba Medika, 2013; 1-8.

Yenkoyan K, Grigoryan A, Fereshetyan K, Yepremyan D. Advances in understanding the pathophysiology of autism spectrum disorders. Behavioral Brain Research, 2017; 331: 92–101.

Li Q, Zhou JM. The microbiotagutbrain axis and its potential therapeutic role in autism spectrum disorder. Neuroscience, 2016; 324: 131-39.

Di Marco B, Bonaccorso CM, AloisiE D’Antoni, Catania MV. Neuro-inflammatory mechanisms in developmental disorders associated with intellectual disability and autism spectrum disorder: A neuro-immune perspective. CNS & Neurological Disorders-Drug Targets, 2016; 15: 448-58.



  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.