{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:58Z","timestamp":1787027758100,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this retrospective observational study, we gathered data on 135 medication-free individuals aged 6 to 17 years: 90 with NDDs (34 with autism spectrum disorder (ASD), 29 with attention-deficit\/hyperactivity disorder, 14 with intellectual disability, and 13 with tic disorder) and 45 typically developed controls. The variables analyzed were compared using analysis of variance including Bonferroni posthoc testing for pairwise comparisons Significance was defined as p &lt; 0.05. Results: The analysis of variance revealed statistical significance for all evaluated CBC parameters, as well as for the lymphocyte-to-monocyte ratio. Notably, subjects with ASD exhibited increased values of neutrophils, lymphocytes, monocytes, and eosinophils compared to both typically developing subjects and other NDDs. The lymphocyte-to-monocyte ratio was found to be lower in the tic disorder group compared to typically developing subjects. The elevated lymphocyte and monocyte levels in ASD subjects might reflect chronic low-grade inflammation. Conclusions: Consistent with the evidence in literature, statistically significant differences between the NDD group and typically developed subjects in the CBC parameters were found. The principal limitations of this investigation are the restricted sample size and the exclusion of specific NDD subtypes. Future research is needed to evaluate CBC parameters and inflammatory indices in a broader spectrum of NDDs to better understand the immunoinflammatory response specific to each disorder.<\/jats:p>","DOI":"10.3390\/brainsci15090937","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T09:08:52Z","timestamp":1756458532000},"page":"937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hematological Inflammatory Markers Across Neurodevelopmental Disorders: Preliminary Findings of an Observational Retrospective Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3135-6718","authenticated-orcid":false,"given":"Raffaele","family":"Garotti","sequence":"first","affiliation":[{"name":"Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-9099","authenticated-orcid":false,"given":"Maria Pia","family":"Riccio","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Child Neuropsichiatry, AOU Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Staffa","sequence":"additional","affiliation":[{"name":"School of Medicine, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Pezone","sequence":"additional","affiliation":[{"name":"Department of Medical and Translational Sciences, Child Neuropsychiatry, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-2870","authenticated-orcid":false,"given":"Carmela","family":"Bravaccio","sequence":"additional","affiliation":[{"name":"Department of Medical and Translational Sciences, Child Neuropsychiatry, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S2215-0366(16)30376-5","article-title":"Neurodevelopmental disorders","volume":"4","author":"Thapar","year":"2017","journal-title":"Lancet. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2022). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.]. Text Revision.","DOI":"10.1176\/appi.books.9780890425787"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-981-19-7376-5_5","article-title":"Animal Inflammation-Based Models of Neuropsychiatric Disorders","volume":"1411","author":"Demin","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/978-981-19-7376-5_15","article-title":"A Potential Role for Neuroinflammation in ADHD","volume":"1411","author":"Corona","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.molmed.2018.06.008","article-title":"The Impact of Systemic Inflammation on Neurodevelopment","volume":"24","author":"Jiang","year":"2018","journal-title":"Trends Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/HRP.0000000000000326","article-title":"Brick by Brick: Building a Transdiagnostic Understanding of Inflammation in Psychiatry","volume":"30","author":"Thylur","year":"2022","journal-title":"Harv. Rev. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Arteaga-Henr\u00edquez, G., Lugo-Mar\u00edn, J., Gisbert, L., Seti\u00e9n-Ramos, I., Mart\u00ednez-Gallo, M., Pujol-Borrell, R., and Ramos-Quiroga, J.A. (2022). Activation of the Monocyte\/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214329"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"G\u0119dek, A., Modrzejewski, S., G\u0119dek, M., Antosik, A.Z., Mierzejewski, P., and Dominiak, M. (2023). Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in ADHD: A systematic review and meta-analysis. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1258868"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1080\/17520363.2024.2404387","article-title":"Evaluation of primary markers of inflammation and the systemic inflammation index in specific learning disabilities","volume":"18","author":"Kara","year":"2024","journal-title":"Biomark. Med."},{"key":"ref_10","first-page":"e47280","article-title":"Can Red Blood Cell and Platelet Parameters Be Associated with Inflammation in Children with Tic Disorder?","volume":"15","author":"Kara","year":"2023","journal-title":"Cureus"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"LaFlair, G.T., Egbert, J., and Plonsky, L. (2015). A Practical Guide to Bootstrapping Descriptive Statistics, Correlations, T Tests, and ANOVAs. Advancing Quantitative Methods in Second Language Research, Routledge.","DOI":"10.4324\/9781315870908-4"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3343\/alm.2018.38.6.503","article-title":"Complete Blood Count Reference Intervals and Patterns of Changes Across Pediatric, Adult, and Geriatric Ages in Korea","volume":"38","author":"Nah","year":"2018","journal-title":"Ann. Lab. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ferencova, N., Visnovcova, Z., Ondrejka, I., Hrtanek, I., Bujnakova, I., Kovacova, V., Macejova, A., and Tonhajzerova, I. (2023). Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit\/Hyperactivity Disorder at Adolescent Age. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411710"},{"key":"ref_14","first-page":"607","article-title":"Does increased neutrophil-lymphocyte ratio predict autism spectrum disorder?","volume":"19","author":"Kutlu","year":"2018","journal-title":"Alpha Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/5584_2015_145","article-title":"Inflammatory Activity in Autism Spectrum Disorder","volume":"861","author":"Tonhajzerova","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_16","unstructured":"McManus, L.M., and Mitchell, R.N. (2014). Chronic Inflammation. Pathobiology of Human Disease, Academic Press."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pnpbp.2017.02.008","article-title":"Role of infiltrating monocytes\/macrophages in acute and chronic neuroinflammation: Effects on cognition, learning and affective behaviour","volume":"79 Pt A","author":"Minogue","year":"2017","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s10802-025-01303-3","article-title":"Peripheral Blood Monocytes as Biomarkers of Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis","volume":"53","author":"Ju","year":"2025","journal-title":"Res. Child Adolesc. Psychopathol."},{"key":"ref_19","first-page":"73","article-title":"High monocyte level and low lymphocyte to monocyte ratio in autism spectrum disorders","volume":"65","author":"Kasak","year":"2017","journal-title":"Int. J. Dev. Disabil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1176\/appi.ajp.160.9.1691","article-title":"High blood monocyte counts and neopterin levels in children with autistic disorder","volume":"160","author":"Sweeten","year":"2003","journal-title":"Am. J. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jpeds.2015.12.063","article-title":"Comorbidity of Atopic Disorders with Autism Spectrum Disorder and Attention Deficit\/Hyperactivity Disorder","volume":"171","author":"Liao","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.thromres.2022.10.001","article-title":"Step up to the platelet: Role of platelets in inflammation and infection","volume":"231","author":"Carestia","year":"2023","journal-title":"Thromb. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mandel, J., Casari, M., Stepanyan, M., Martyanov, A., and Deppermann, C. (2022). Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073868"},{"key":"ref_24","first-page":"1004","article-title":"Evaluation of Patients with Leukocytosis","volume":"92","author":"Riley","year":"2015","journal-title":"Am. Fam. Physician"},{"key":"ref_25","first-page":"260","article-title":"Can Hematological Parameters Indicate Possible Inflammatory Mechanisms in Children with Intellectual Disability?","volume":"42","author":"Mutlu","year":"2020","journal-title":"J. Clin. Pract. Res."},{"key":"ref_26","first-page":"129","article-title":"Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: A systematic review","volume":"22","author":"Cortese","year":"2023","journal-title":"World Psychiatry Off. J. World Psychiatr. Assoc. (WPA)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1001\/jamapsychiatry.2019.3523","article-title":"Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence","volume":"77","author":"Dalsgaard","year":"2020","journal-title":"JAMA Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.it.2022.01.007","article-title":"Maternal inflammation and its ramifications on fetal neurodevelopment","volume":"43","author":"Kwon","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1126\/science.aag3194","article-title":"Maternal immune activation: Implications for neuropsychiatric disorders","volume":"353","author":"Estes","year":"2016","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ellul, P., Maruani, A., Peyre, H., Vantalon, V., Hoareau, D., Tiercelin, H., Rosenzwajg, M., Klatzmann, D., and Delorme, R. (2023). Abnormal neutrophil-to-lymphocyte ratio in children with autism spectrum disorder and history of maternal immune activation. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-49789-5"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ellul, P., Maruani, A., Vantalon, V., Humeau, E., Amestoy, A., Anchordoqui, A., Atzori, P., Baleyte, J.-M., Benmansour, S., and Bonnot, O. (2023). Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-45060-z"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.pbb.2019.05.005","article-title":"Neuroinflammation as a risk factor for attention deficit hyperactivity disorder","volume":"182","author":"Dunn","year":"2019","journal-title":"Pharmacol. Biochem. Behav."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/9\/937\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:34:37Z","timestamp":1760034877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/9\/937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":32,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["brainsci15090937"],"URL":"https:\/\/doi.org\/10.3390\/brainsci15090937","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,28]]}}}