Research Article
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The Role of Systemic Inflammation and Haematological Parameters in Autism

Year 2025, Volume: 46 Issue: 2, 298 - 303, 30.06.2025

Elif Abanoz , Merve Soyhan , Ayla Uzun Cicek , Ali Güven Say , Serkan Bolat

https://doi.org/10.17776/csj.1639387

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in social communication and repetitive behaviors. Emerging evidence suggests that ASD may also involve systemic inflammatory processes. This study aimed to assess systemic inflammation in children with ASD using hematological biomarkers and to investigate the association between these markers and autism severity. A total of 75 children with ASD (mean age: 4.37±1.01 years) and 75 age- and sex-matched healthy controls (mean age: 4.41±1.06 years) were included. Complete blood count data were used to calculate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). Compared to controls, the ASD group showed significantly higher levels of leukocytes (p=0.011), neutrophils (p=0.001), monocytes (p<0.001), NLR (p=0.005), SII (p=0.001), and SIRI (p<0.001). Moreover, CARS scores, indicating autism severity, were positively correlated with these inflammatory markers (e.g., SIRI: r=0.403, p<0.001; monocyte: r=0.362, p<0.001). These findings suggest that systemic inflammation may contribute to the pathophysiology of ASD and that hematological indices could serve as accessible biomarkers for clinical evaluation.

Keywords

ASD SII SIRI Inflammation Haematological biomarkers

Ethical Statement

This study was approved by the local Ethics Committee of the Medical Faculty of Sivas Cumhuriyet University.

References

  • [1] American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders DSM 5 TR (5th ed, text revision), 2022.
  • [2] Maenner M.J., Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020, MMWR. Surveill. Summ., 72 (2023).
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  • [5] Masi A., Quintana D., Glozier N., Lloyd A., Hickie I., Guastella A., Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis, Mol. Psychiatry, 20 (4) (2015) 440-446.
  • [6] Xiao T.S., Innate immunity and inflammation, Cell. Mol. Immunol., 14 (1) (2017) 1-3.
  • [7] Osimo E.F., Cardinal R.N., Jones P.B., Khandaker G.M., Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: an electronic health record-based study, Psychoneuroendocrinology, 91 (2018) 226-234.
  • [8] Mazza M.G., Lucchi S., Tringali A.G.M., Rossetti A., Botti E.R., Clerici M., Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: a meta-analysis, Prog. Neuropsychopharmacol. Biol. Psychiatry, 84 (2018) 229-236.
  • [9] Catak Z., Uzmez E., Ozturk N., Ugur K., 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., 1 (3) (2018) 106-110.
  • [10] Song Y., Zhao Y., Shu Y., Zhang L., Cheng W., Wang L., Shu M., Xue B., Wang R., Feng Z., Combination model of neutrophil to high-density lipoprotein ratio and system inflammation response index is more valuable for predicting peripheral arterial disease in type 2 diabetic patients: A cross-sectional study, Front. Endocrinol., 14 (2023) 1100453.
  • [11] Jin Z., Wu Q., Chen S., Gao J., Li X., Zhang X., Zhou Y., He D., Cheng Z., Zhu Y., The associations of two novel inflammation indexes, SII and SIRI with the risks for cardiovascular diseases and all-cause mortality: a ten-year follow-up study in 85,154 individuals, J. Inflamm. Res., (2021) 131-140.
  • [12] Hu B., Yang X.R., Xu Y., Sun Y.F., Sun C., Guo W., Zhang X., Wang W.M., Qiu S.J., Zhou J., Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma, Clin. Cancer Res., 20 (23) (2014) 6212-6222.
  • [13] Qi Q., Zhuang L., Shen Y., Geng Y., Yu S., Chen H., Liu L., Meng Z., Wang P., Chen Z., A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy, Cancer, 122 (14) (2016) 2158-2167.
  • [14] Ninla-Aesong P., Kietdumrongwong P., Neupane S.P., Puangsri P., Jongkrijak H., Chotipong P., Kaewpijit P., Relative value of novel systemic immune-inflammatory indices and classical hematological parameters in predicting depression, suicide attempts and treatment response, Sci. Rep., 14 (1) (2024) 19018.
  • [15] Schopler E., Reichler R.J., DeVellis R.F., Daly K., Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS), J. Autism Dev. Disord., (1980).
  • [16] Gassaloğlu S.İ., Baykara B., Avcil S., Demiral Y., Çocukluk Otizmi Derecelendirme Ölçeği Türkçe formunun geçerlik ve güvenilirlik çalışması, Türk Psikiyatri Derg., 27 (4) (2016) 266-274.
  • [17] Xu N., Li X., Zhong Y., Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders, Mediators Inflamm., 2015 (1) (2015) 531518.
  • [18] Careaga M., Van de Water J., Ashwood P., Immune dysfunction in autism: a pathway to treatment, Neurotherapeutics, 7 (3) (2010) 283-292.
  • [19] Masi A., Glozier N., Dale R., Guastella A.J., The immune system, cytokines, and biomarkers in autism spectrum disorder, Neurosci. Bull., 33 (2017) 194-204.
  • [20] Anastasescu C.M., Gheorman V., Stoicanescu E.-C., Popescu F., Gheorman V., Udriștoiu I., Immunological biomarkers in Autism Spectrum Disorder: the role of TNF-Alpha and dependent trends in serum IL-6 and CXCL8, Life, 14 (9) (2024) 1201.
  • [21] Saghazadeh A., Ataeinia B., Keynejad K., Abdolalizadeh A., Hirbod-Mobarakeh A., Rezaei N., A meta-analysis of pro-inflammatory cytokines in autism spectrum disorders: Effects of age, gender, and latitude, J. Psychiatr. Res., 115 (2019) 90-102.
  • [22] Zulfic Z., Weickert C.S., Weickert T.W., Liu D., Myles N., Galletly C., Neutrophil-lymphocyte ratio–a simple, accessible measure of inflammation, morbidity and prognosis in psychiatric disorders?, Australas. Psychiatry, 28 (4) (2020) 454-458.
  • [23] Bhikram T., Sandor P., Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients, Brain Behav. Immun., 105 (2022) 237-246.
  • [24] Hosseini S., Shafiabadi N., Khanzadeh M., Ghaedi A., Ghorbanzadeh R., Azarhomayoun A., Bazrgar A., Pezeshki J., Bazrafshan H., Khanzadeh S., Neutrophil to lymphocyte ratio in Parkinson’s disease: A systematic review and meta-analysis, BMC Neurol., 23 (1) (2023) 333.
  • [25] Özyurt G., Binici N.C., Increased neutrophil-lymphocyte ratios in depressive adolescents is correlated with the severity of depression, Psychiatry Res., 268 (2018) 426-431.
  • [26] Özyurt G., Binici N.C., The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in adolescent obsessive-compulsive disorder: Does comorbid anxiety disorder affect inflammatory response?, Psychiatry Res., 272 (2019) 311-315.
  • [27] Avcil S., Evaluation of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as inflammatory markers in children with attention‐deficit hyperactivity disorder, Psychiatry Clin. Neurosci., 72 (7) (2018) 522-530.
  • [28] Önder A., Gizli Çoban Ö., Sürer Adanır A., ‘Elevated neutrophil-to-lymphocyte ratio in children and adolescents with attention-deficit/hyperactivity disorder, Int. J. Psychiatry Clin. Pract., 25 (1) (2021) 43-48.
  • [29] Kutlu A., Binici N.C., Does increased neutrophil-lymphocyte ratio predict autism spectrum disorder?, Anadolu Psikiyatri Derg., 19 (6) (2018) 607-614.
  • [30] Tural Hesapcioglu S., Kasak M., Cıtak Kurt A.N., Ceylan M.F., High monocyte level and low lymphocyte to monocyte ratio in autism spectrum disorders, Int. J. Dev. Disabil., 65 (2) (2019) 73-81.
  • [31] Dziedzic E.A., Gąsior J.S., Tuzimek A., Paleczny J., Junka A., Dąbrowski M., Jankowski P., Investigation of the associations of novel inflammatory biomarkers—Systemic Inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI)—With the severity of coronary artery disease and acute coronary syndrome occurrence, Int. J. Mol. Sci., 23 (17) (2022) 9553.
  • [32] İnaltekin A., Yağcı İ., Evaluation of simple markers of inflammation and systemic immune inflammation index in schizophrenia, bipolar disorder patients and healthy controls, Turk. J. Psychiatry, 34 (1) (2021) 11.
  • [33] Canlı D., Evaluation of systemic immune-inflammation index, systemic inflammatory response index and hematologic inflammatory parameters in generalized anxiety disorder: a controlled study, Anatol. Curr. Med. J., 6 (2) (2024) 161-167.
  • [34] Avşar P.A., Kara T., Kocaman O., Akkuş M., Evaluation of primary markers of inflammation and the systemic inflammation index in specific learning disabilities, Biomark. Med., 18 (20) (2024) 907-916.
  • [35] Hughes H.K., Onore C.E., Careaga M., Rogers S.J., Ashwood P., Increased monocyte production of IL-6 after toll-like receptor activation in children with autism spectrum disorder (ASD) is associated with repetitive and restricted behaviors, Brain Sci., 12 (2) (2022) 220.
  • [36] 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., 25 (1) (2011) 40-45.
  • [37] Inga Jácome M.C., Morales Chacón L.M., Vera Cuesta H., Maragoto Rizo C., Whilby Santiesteban M., Ramos Hernandez L., Noris García E., González Fraguela M.E., Fernandez Verdecia C.I., Vegas Hurtado Y., Peripheral inflammatory markers contributing to comorbidities in autism, Behav. Sci., 6 (4) (2016) 29.
  • [38] Topal Z., Tufan A.E., Karadag M., Gokcen C., Akkaya C., Sarp A.S., Bahsi I., Kilinc M., Evaluation of peripheral inflammatory markers, serum B12, folate, ferritin levels and clinical correlations in children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), Nord. J. Psychiatry, 76 (2) (2022) 150-157.
  • [39] Marsland A.L., Prather A.A., Petersen K.L., Cohen S., Manuck S.B., Antagonistic characteristics are positively associated with inflammatory markers independently of trait negative emotionality, Brain Behav. Immun., 22 (5) (2008) 753-761.
  • [40] Krefft M., Frydecka D., Zalsman G., Krzystek-Korpacka M., Śmigiel R., Gębura K., Bogunia-Kubik K., Misiak B., A pro-inflammatory phenotype is associated with behavioural traits in children with Prader–Willi syndrome, Eur. Child Adolesc. Psychiatry, 30 (2021) 899-908.

Year 2025, Volume: 46 Issue: 2, 298 - 303, 30.06.2025

Elif Abanoz , Merve Soyhan , Ayla Uzun Cicek , Ali Güven Say , Serkan Bolat

https://doi.org/10.17776/csj.1639387

Abstract

References

  • [1] American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders DSM 5 TR (5th ed, text revision), 2022.
  • [2] Maenner M.J., Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020, MMWR. Surveill. Summ., 72 (2023).
  • [3] Limperopoulos C., Bassan H., Sullivan N.R., Soul J.S., Robertson R.L. Jr., Moore M., Ringer S.A., Volpe J.J., du Plessis A.J., Positive screening for autism in ex-preterm infants: prevalence and risk factors, Pediatrics, 121 (4) (2008) 758-765.
  • [4] Gładysz D., Krzywdzińska A., Hozyasz K.K., Immune abnormalities in autism spectrum disorder—could they hold promise for causative treatment?, Mol. Neurobiol., 55 (2018) 6387-6435.
  • [5] Masi A., Quintana D., Glozier N., Lloyd A., Hickie I., Guastella A., Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis, Mol. Psychiatry, 20 (4) (2015) 440-446.
  • [6] Xiao T.S., Innate immunity and inflammation, Cell. Mol. Immunol., 14 (1) (2017) 1-3.
  • [7] Osimo E.F., Cardinal R.N., Jones P.B., Khandaker G.M., Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: an electronic health record-based study, Psychoneuroendocrinology, 91 (2018) 226-234.
  • [8] Mazza M.G., Lucchi S., Tringali A.G.M., Rossetti A., Botti E.R., Clerici M., Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: a meta-analysis, Prog. Neuropsychopharmacol. Biol. Psychiatry, 84 (2018) 229-236.
  • [9] Catak Z., Uzmez E., Ozturk N., Ugur K., 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., 1 (3) (2018) 106-110.
  • [10] Song Y., Zhao Y., Shu Y., Zhang L., Cheng W., Wang L., Shu M., Xue B., Wang R., Feng Z., Combination model of neutrophil to high-density lipoprotein ratio and system inflammation response index is more valuable for predicting peripheral arterial disease in type 2 diabetic patients: A cross-sectional study, Front. Endocrinol., 14 (2023) 1100453.
  • [11] Jin Z., Wu Q., Chen S., Gao J., Li X., Zhang X., Zhou Y., He D., Cheng Z., Zhu Y., The associations of two novel inflammation indexes, SII and SIRI with the risks for cardiovascular diseases and all-cause mortality: a ten-year follow-up study in 85,154 individuals, J. Inflamm. Res., (2021) 131-140.
  • [12] Hu B., Yang X.R., Xu Y., Sun Y.F., Sun C., Guo W., Zhang X., Wang W.M., Qiu S.J., Zhou J., Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma, Clin. Cancer Res., 20 (23) (2014) 6212-6222.
  • [13] Qi Q., Zhuang L., Shen Y., Geng Y., Yu S., Chen H., Liu L., Meng Z., Wang P., Chen Z., A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy, Cancer, 122 (14) (2016) 2158-2167.
  • [14] Ninla-Aesong P., Kietdumrongwong P., Neupane S.P., Puangsri P., Jongkrijak H., Chotipong P., Kaewpijit P., Relative value of novel systemic immune-inflammatory indices and classical hematological parameters in predicting depression, suicide attempts and treatment response, Sci. Rep., 14 (1) (2024) 19018.
  • [15] Schopler E., Reichler R.J., DeVellis R.F., Daly K., Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS), J. Autism Dev. Disord., (1980).
  • [16] Gassaloğlu S.İ., Baykara B., Avcil S., Demiral Y., Çocukluk Otizmi Derecelendirme Ölçeği Türkçe formunun geçerlik ve güvenilirlik çalışması, Türk Psikiyatri Derg., 27 (4) (2016) 266-274.
  • [17] Xu N., Li X., Zhong Y., Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders, Mediators Inflamm., 2015 (1) (2015) 531518.
  • [18] Careaga M., Van de Water J., Ashwood P., Immune dysfunction in autism: a pathway to treatment, Neurotherapeutics, 7 (3) (2010) 283-292.
  • [19] Masi A., Glozier N., Dale R., Guastella A.J., The immune system, cytokines, and biomarkers in autism spectrum disorder, Neurosci. Bull., 33 (2017) 194-204.
  • [20] Anastasescu C.M., Gheorman V., Stoicanescu E.-C., Popescu F., Gheorman V., Udriștoiu I., Immunological biomarkers in Autism Spectrum Disorder: the role of TNF-Alpha and dependent trends in serum IL-6 and CXCL8, Life, 14 (9) (2024) 1201.
  • [21] Saghazadeh A., Ataeinia B., Keynejad K., Abdolalizadeh A., Hirbod-Mobarakeh A., Rezaei N., A meta-analysis of pro-inflammatory cytokines in autism spectrum disorders: Effects of age, gender, and latitude, J. Psychiatr. Res., 115 (2019) 90-102.
  • [22] Zulfic Z., Weickert C.S., Weickert T.W., Liu D., Myles N., Galletly C., Neutrophil-lymphocyte ratio–a simple, accessible measure of inflammation, morbidity and prognosis in psychiatric disorders?, Australas. Psychiatry, 28 (4) (2020) 454-458.
  • [23] Bhikram T., Sandor P., Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients, Brain Behav. Immun., 105 (2022) 237-246.
  • [24] Hosseini S., Shafiabadi N., Khanzadeh M., Ghaedi A., Ghorbanzadeh R., Azarhomayoun A., Bazrgar A., Pezeshki J., Bazrafshan H., Khanzadeh S., Neutrophil to lymphocyte ratio in Parkinson’s disease: A systematic review and meta-analysis, BMC Neurol., 23 (1) (2023) 333.
  • [25] Özyurt G., Binici N.C., Increased neutrophil-lymphocyte ratios in depressive adolescents is correlated with the severity of depression, Psychiatry Res., 268 (2018) 426-431.
  • [26] Özyurt G., Binici N.C., The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in adolescent obsessive-compulsive disorder: Does comorbid anxiety disorder affect inflammatory response?, Psychiatry Res., 272 (2019) 311-315.
  • [27] Avcil S., Evaluation of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as inflammatory markers in children with attention‐deficit hyperactivity disorder, Psychiatry Clin. Neurosci., 72 (7) (2018) 522-530.
  • [28] Önder A., Gizli Çoban Ö., Sürer Adanır A., ‘Elevated neutrophil-to-lymphocyte ratio in children and adolescents with attention-deficit/hyperactivity disorder, Int. J. Psychiatry Clin. Pract., 25 (1) (2021) 43-48.
  • [29] Kutlu A., Binici N.C., Does increased neutrophil-lymphocyte ratio predict autism spectrum disorder?, Anadolu Psikiyatri Derg., 19 (6) (2018) 607-614.
  • [30] Tural Hesapcioglu S., Kasak M., Cıtak Kurt A.N., Ceylan M.F., High monocyte level and low lymphocyte to monocyte ratio in autism spectrum disorders, Int. J. Dev. Disabil., 65 (2) (2019) 73-81.
  • [31] Dziedzic E.A., Gąsior J.S., Tuzimek A., Paleczny J., Junka A., Dąbrowski M., Jankowski P., Investigation of the associations of novel inflammatory biomarkers—Systemic Inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI)—With the severity of coronary artery disease and acute coronary syndrome occurrence, Int. J. Mol. Sci., 23 (17) (2022) 9553.
  • [32] İnaltekin A., Yağcı İ., Evaluation of simple markers of inflammation and systemic immune inflammation index in schizophrenia, bipolar disorder patients and healthy controls, Turk. J. Psychiatry, 34 (1) (2021) 11.
  • [33] Canlı D., Evaluation of systemic immune-inflammation index, systemic inflammatory response index and hematologic inflammatory parameters in generalized anxiety disorder: a controlled study, Anatol. Curr. Med. J., 6 (2) (2024) 161-167.
  • [34] Avşar P.A., Kara T., Kocaman O., Akkuş M., Evaluation of primary markers of inflammation and the systemic inflammation index in specific learning disabilities, Biomark. Med., 18 (20) (2024) 907-916.
  • [35] Hughes H.K., Onore C.E., Careaga M., Rogers S.J., Ashwood P., Increased monocyte production of IL-6 after toll-like receptor activation in children with autism spectrum disorder (ASD) is associated with repetitive and restricted behaviors, Brain Sci., 12 (2) (2022) 220.
  • [36] 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., 25 (1) (2011) 40-45.
  • [37] Inga Jácome M.C., Morales Chacón L.M., Vera Cuesta H., Maragoto Rizo C., Whilby Santiesteban M., Ramos Hernandez L., Noris García E., González Fraguela M.E., Fernandez Verdecia C.I., Vegas Hurtado Y., Peripheral inflammatory markers contributing to comorbidities in autism, Behav. Sci., 6 (4) (2016) 29.
  • [38] Topal Z., Tufan A.E., Karadag M., Gokcen C., Akkaya C., Sarp A.S., Bahsi I., Kilinc M., Evaluation of peripheral inflammatory markers, serum B12, folate, ferritin levels and clinical correlations in children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), Nord. J. Psychiatry, 76 (2) (2022) 150-157.
  • [39] Marsland A.L., Prather A.A., Petersen K.L., Cohen S., Manuck S.B., Antagonistic characteristics are positively associated with inflammatory markers independently of trait negative emotionality, Brain Behav. Immun., 22 (5) (2008) 753-761.
  • [40] Krefft M., Frydecka D., Zalsman G., Krzystek-Korpacka M., Śmigiel R., Gębura K., Bogunia-Kubik K., Misiak B., A pro-inflammatory phenotype is associated with behavioural traits in children with Prader–Willi syndrome, Eur. Child Adolesc. Psychiatry, 30 (2021) 899-908.
There are 40 citations in total.

Details

Primary Language English
Subjects Metabolic Medicine
Journal Section Natural Sciences
Authors

Elif Abanoz 0000-0002-9214-4735

Merve Soyhan 0009-0001-9238-5256

Ayla Uzun Cicek 0000-0003-2274-3457

Ali Güven Say 0009-0009-4413-1145

Serkan Bolat 0000-0002-8669-8782

Publication Date June 30, 2025
Submission Date February 13, 2025
Acceptance Date June 11, 2025
Published in Issue Year 2025Volume: 46 Issue: 2

Cite

APA Abanoz, E., Soyhan, M., Uzun Cicek, A., Say, A. G., et al. (2025). The Role of Systemic Inflammation and Haematological Parameters in Autism. Cumhuriyet Science Journal, 46(2), 298-303. https://doi.org/10.17776/csj.1639387