Objective:
The role of inflammation in psychopathology has received great attention over the past decades. Immune system dysfunction and altered cytokine levels have been reported in most psychiatric disorders in adults. Few data are available regarding children and adolescents (C&A), or regarding the relationship between cytokine levels and psychosocial stress. This study investigates the profile of the most described cytokines in a sample of C&A inpatients affected by an acute psychiatric condition requiring hospitalization, in comparison with healthy subjects, as well as possible associations between psychosocial stressors and psychopathology and/or cytokine concentrations.
Methods:
Patients with a diagnosis of Affective, Anxiety, Adjustment, Psychotic, Obsessive-Compulsive, Tic or Tourette Disorders were consecutively recruited from our clinic between June 2010 and February 2012. Controls were recruited from the same geographic area. All subjects were between 8 and 17 years old. Twelve cytokines are compared: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL_10, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IFN-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1. Psychosocial stress was measured through the Stressful Life Events Scale, Child and Parents versions (SLES-C and SLES-P) and the evaluation of the family integrity.
Results:
One hundred and eleven subjects (77C&A inpatients and 34 healthy controls), of which 54 were males (49%), with a median (interquartile range) age of 16 (13.7-17.3) years, were included in this study. IL-1β, IL6, IL8, IP-10, MCP-1 and monocytes were found to be significantly higher in the patient group (p<0.05). Differences were confirmed when adjusting by BMI, age, gender and drug intake at admission for all cytokines except MCP-1. IL-8 and IL-1β were also higher throughout the different diagnostic categories, than in control group (p<0.05). Stress measures were higher in patients. A significant correlation was found between stress measured by the SLES and some inflammatory markers: SLES_C with IL-1β, IL-8, MCP-1, and SLES_P with IL-1β and monocytes absolute and relative counts (Spearman's r between 0.219 and 0.297, p<0.05). Logistic regression identified the following variables as independent predictors of the patient condition, (odds ratio per quartile, p-value): IL8 (1, 0.9, 12.1, 32.0, p=0.044), IP10 (1, 14.1, 2.5, 3.7, p=0.044), monocyte absolute count (1, 1.1, 6.0, 19.4, p=0.030).
Conclusions:
Results show elevated inflammation markers from the innate immune system across C&A acute psychiatric diagnosis, and suggest a link between psychopathology, inflammation and stress. Inflammatory markers resulted predictors of patient status. These exploratory results are coherent with current psychoneuroimmunology and neurodevelopmental investigations.
Citing Articles
Peripheral Blood Monocytes as Biomarkers of Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis.
Ju X, Zhang P, Li Q, Bai Q, Hu B, Xu J
Res Child Adolesc Psychopathol. 2025; .
PMID: 40053221
DOI: 10.1007/s10802-025-01303-3.
First-episode psychiatric disorder risk from SARS-CoV-2 infection: A clinical analysis with Chinese psychiatric inpatients.
Xie Y, Xu Z, Zhang Y, Li Y, Du P, Wang C
J Biomed Res. 2024; 39(1):50-60.
PMID: 38807424
PMC: 11873594.
DOI: 10.7555/JBR.38.20240005.
Immune and oxidative stress biomarkers in pediatric psychosis and psychosis-risk: Meta-analyses and systematic review.
Taylor J, Bermudez-Gomez J, Zhou M, Gomez O, Ganz-Leary C, Palacios-Ordonez C
Brain Behav Immun. 2023; 117:1-11.
PMID: 38141839
PMC: 10932921.
DOI: 10.1016/j.bbi.2023.12.019.
Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study.
Kuang N, Liu Z, Yu G, Wu X, Becker B, Fan H
BMC Med. 2023; 21(1):291.
PMID: 37542243
PMC: 10403847.
DOI: 10.1186/s12916-023-02920-9.
Impact of the COVID-19 pandemic on adults with Fetal Alcohol Spectrum Disorder: linking immune function to mental health status.
Bodnar T, Chao A, Holman P, Ellis L, Raineki C, Weinberg J
Front Neurosci. 2023; 17:1214100.
PMID: 37539379
PMC: 10394466.
DOI: 10.3389/fnins.2023.1214100.
Association Between Inflammatory Biomarkers and Mental Health Symptoms in Middle Eastern Refugees in the US.
Ghandour M, Yamin J, Arnetz J, Lumley M, Stemmer P, Burghardt P
Cureus. 2022; 14(8):e28246.
PMID: 36158450
PMC: 9498960.
DOI: 10.7759/cureus.28246.
Cytokine profile of pediatric patients with obsessive-compulsive and/or movement disorder symptoms: A review.
Fabricius R, Sorensen C, Skov L, Mol Debes N
Front Pediatr. 2022; 10:893815.
PMID: 36061386
PMC: 9437446.
DOI: 10.3389/fped.2022.893815.
Cytokine alterations in pediatric internalizing disorders: Systematic review and exploratory multi-variate meta-analysis.
Howe A, Lynch D
Brain Behav Immun Health. 2022; 24:100490.
PMID: 35880170
PMC: 9307453.
DOI: 10.1016/j.bbih.2022.100490.
Molecular Biomarkers for Pediatric Depressive Disorders: A Narrative Review.
Lee J, Chi S, Lee M
Int J Mol Sci. 2021; 22(18).
PMID: 34576215
PMC: 8464852.
DOI: 10.3390/ijms221810051.
Immunological Effects of an Add-On Physical Exercise Therapy in Depressed Adolescents and Its Interplay with Depression Severity.
Wunram H, Oberste M, Hamacher S, Neufang S, Grote N, Krischer M
Int J Environ Res Public Health. 2021; 18(12).
PMID: 34204400
PMC: 8296386.
DOI: 10.3390/ijerph18126527.
Immunological Dysfunction in Tourette Syndrome and Related Disorders.
Hsu C, Wong L, Lee W
Int J Mol Sci. 2021; 22(2).
PMID: 33467014
PMC: 7839977.
DOI: 10.3390/ijms22020853.
What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders?.
Martino D, Johnson I, Leckman J
Front Neurol. 2020; 11:567407.
PMID: 33041996
PMC: 7525089.
DOI: 10.3389/fneur.2020.567407.
Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues.
Tonhajzerova I, Sekaninova N, Bona Olexova L, Visnovcova Z
Int J Mol Sci. 2020; 21(7).
PMID: 32230840
PMC: 7177743.
DOI: 10.3390/ijms21072317.
Immunity in Gilles de la Tourette-Syndrome: Results From a Cerebrospinal Fluid Study.
Baumgaertel C, Skripuletz T, Kronenberg J, Stangel M, Schwenkenbecher P, Sinke C
Front Neurol. 2019; 10:732.
PMID: 31333575
PMC: 6621640.
DOI: 10.3389/fneur.2019.00732.
Influence of Inflammatory and Oxidative Stress Pathways on Longitudinal Symptom Experiences in Children With Leukemia.
Hockenberry M, Pan W, Scheurer M, Hooke M, Taylor O, Koerner K
Biol Res Nurs. 2019; 21(5):458-465.
PMID: 31315444
PMC: 6854429.
DOI: 10.1177/1099800419863160.
Autoantibodies, elevated cytokines, and neurocognitive abnormalities in offspring of women with systemic lupus erythematosus: comparison with healthy controls.
Gariup M, Lera-Miguel S, Torres F, Varela E, Serra-Pages C, Gonzalez-Navarro A
Clin Rheumatol. 2019; 38(9):2529-2539.
PMID: 31020474
DOI: 10.1007/s10067-019-04495-4.
Inflammatory Profiles in Depressed Adolescents Treated with Fluoxetine: An 8-Week Follow-up Open Study.
Perez-Sanchez G, Becerril-Villanueva E, Arreola R, Martinez-Levy G, Hernandez-Gutierrez M, Velasco-Velasquez M
Mediators Inflamm. 2019; 2018:4074051.
PMID: 30662368
PMC: 6312587.
DOI: 10.1155/2018/4074051.
Chronic Stress in Children and Adolescents: A Review of Biomarkers for Use in Pediatric Research.
M Condon E
Biol Res Nurs. 2018; 20(5):473-496.
PMID: 29865855
PMC: 6346321.
DOI: 10.1177/1099800418779214.
Inflammation, Stress Response, and Redox Dysregulation Biomarkers: Clinical Outcomes and Pharmacological Implications for Psychosis.
Schiavone S, Trabace L
Front Psychiatry. 2017; 8:203.
PMID: 29118723
PMC: 5660996.
DOI: 10.3389/fpsyt.2017.00203.
Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events.
Lopizzo N, Tosato S, Begni V, Tomassi S, Cattane N, Barcella M
Transl Psychiatry. 2017; 7(2):e1042.
PMID: 28221367
PMC: 5438034.
DOI: 10.1038/tp.2017.5.