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Inflammatory cytokines in and cognitive function of adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder

Published online by Cambridge University Press:  19 October 2021

Mu-Hong Chen Open the ORCID record for Mu-Hong Chen [Opens in a new window] ,
Ju-Wei Hsu ,
Kai-Lin Huang ,
Shih-Jen Tsai ,
Pei-Chi Tu  and
Ya-Mei Bai
Mu-Hong Chen
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Ju-Wei Hsu*
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Kai-Lin Huang
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Shih-Jen Tsai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Pei-Chi Tu
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
Ya-Mei Bai*
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
*
* Authors for correspondence: Ya-Mei Bai, MD, PhD Email: ymbi@mail2000.com.tw; Ju-Wei Hsu, MD Email: jwhsu@vghtpe.gov.tw
* Authors for correspondence: Ya-Mei Bai, MD, PhD Email: ymbi@mail2000.com.tw; Ju-Wei Hsu, MD Email: jwhsu@vghtpe.gov.tw
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Abstract

Background

Few studies have explored the complex relationship of pro- and anti-inflammatory cytokines with cognitive function in adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder.

Methods

In total, 26, 35, and 29 adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder, respectively, and 22 age- and sex-matched controls were included in the current study. Cytokines, namely interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP), were assessed. The Wisconsin Card Sorting Test (WCST) and the working memory task were administered to assess cognitive function.

Results

Using generalized linear models with adjustment for demographic data and clinical symptoms, patients with bipolar disorder were found to exhibit the highest levels of CRP (P = .023), IL-6 (P = .022), and TNF-α (P = .011), and had the lowest IL-2 levels (P = .034) among the four groups. According to the results of the WCST and working memory task, adolescents with schizophrenia exhibited the lowest performance in cognitive function. In addition, among the assessed cytokines, only CRP levels (P = .027) were negatively associated with WCST scores.

Discussion

Dysregulated pro- and anti-inflammatory cytokines and impaired cognitive functioning were observed in first-episode adolescent-onset schizophrenia, bipolar disorder, and major depressive disorder. The altered cytokine profiles may play important roles in the pathophysiology of schizophrenia, bipolar disorder, and major depressive disorder.

Keywords

First episodeadolescentcytokinecognitionsevere mental disorder
Type
Original Research
Information
CNS Spectrums , Volume 28 , Issue 1 , February 2023 , pp. 70 - 77
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Foulkes, L, Blakemore, SJ. Studying individual differences in human adolescent brain development. Nat Neurosci. 2018;21(3):315–323.CrossRefGoogle ScholarPubMed
van der Werf, M, Hanssen, M, Kohler, S, et al. Systematic review and collaborative recalculation of 133,693 incident cases of schizophrenia. Psychol Med. 2014;44(1):9–16.CrossRefGoogle ScholarPubMed
Bolton, S, Warner, J, Harriss, E, Geddes, J, Saunders, KEA. Bipolar disorder: trimodal age-at-onset distribution. Bipolar Disord. 2021;23(4):341–356.CrossRefGoogle ScholarPubMed
Lewinsohn, PM, Rohde, P, Seeley, JR. Major depressive disorder in older adolescents: prevalence, risk factors, and clinical implications. Clin Psychol Rev. 1998;18(7):765–794.CrossRefGoogle ScholarPubMed
Noto, MN, Maes, M, Nunes, SOV, et al. Activation of the immune-inflammatory response system and the compensatory immune-regulatory system in antipsychotic naive first episode psychosis. Eur Neuropsychopharmacol. 2019;29(3):416–431.CrossRefGoogle ScholarPubMed
Cakici, N, Sutterland, AL, Penninx, B, Dalm, VA, de Haan, L, van Beveren, NJM. Altered peripheral blood compounds in drug-naive first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis. Brain Behav Immun. 2020;88:547–558.CrossRefGoogle ScholarPubMed
Lesh, TA, Careaga, M, Rose, DR, et al. Cytokine alterations in first-episode schizophrenia and bipolar disorder: relationships to brain structure and symptoms. J Neuroinflammation. 2018;15(1):165.CrossRefGoogle ScholarPubMed
Horsdal, HT, Kohler-Forsberg, O, Benros, ME, Gasse, C. C-reactive protein and white blood cell levels in schizophrenia, bipolar disorders and depression—associations with mortality and psychiatric outcomes: a population-based study. Eur Psychiatry. 2017;44:164–172.CrossRefGoogle ScholarPubMed
Goldsmith, DR, Rapaport, MH, Miller, BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21(12):1696–1709.CrossRefGoogle ScholarPubMed
Bombin, I, Mayoral, M, Castro-Fornieles, J, et al. Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses. Psychol Med. 2013;43(4):757–768.CrossRefGoogle ScholarPubMed
Barrett, SL, Mulholland, CC, Cooper, SJ, Rushe, TM. Patterns of neurocognitive impairment in first-episode bipolar disorder and schizophrenia. Br J Psychiatry. 2009;195(1):67–72.CrossRefGoogle ScholarPubMed
Chen, C, Jiang, WH, Wang, W, et al. Impaired visual, working, and verbal memory in first-episode, drug-naive patients with major depressive disorder in a Chinese population. PLoS One. 2018;13(4):e0196023.CrossRefGoogle ScholarPubMed
Ahern, E, Semkovska, M. Cognitive functioning in the first-episode of major depressive disorder: a systematic review and meta-analysis. Neuropsychology. 2017;31(1):52–72.CrossRefGoogle ScholarPubMed
Orhan, F, Fatouros-Bergman, H, Schwieler, L, et al. First-episode psychosis patients display increased plasma IL-18 that correlates with cognitive dysfunction. Schizophr Res. 2018;195:406–408.CrossRefGoogle ScholarPubMed
Tian, H, Li, G, Xu, G, et al. Inflammatory cytokines derived from peripheral blood contribute to the modified electroconvulsive therapy-induced cognitive deficits in major depressive disorder. Eur Arch Psychiatry Clin Neurosci. 2021;271(3):475–485.CrossRefGoogle Scholar
Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.CrossRefGoogle ScholarPubMed
Young, RC, Biggs, JT, Ziegler, VE, Meyer, DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429–435.CrossRefGoogle ScholarPubMed
Andreasen, NC, Olsen, S. Negative v positive schizophrenia. Definition and validation. Arch Gen Psychiatry. 1982;39(7):789–794.CrossRefGoogle ScholarPubMed
Chen, MH, Li, CT, Lin, WC, et al. Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion. J Affect Disord. 2018;241:1–7.CrossRefGoogle ScholarPubMed
Hua, MH, Chen, MH, Hsu, JW, et al. Proinflammatory cytokine dysregulation and cognitive dysfunction among patients with remitted bipolar I and II disorders. J Affect Disord. 2021;281:738–743.CrossRefGoogle ScholarPubMed
Chen, MH, Kao, ZK, Chang, WC, et al. Increased proinflammatory cytokines, executive dysfunction, and reduced gray matter volumes in first-episode bipolar disorder and major depressive disorder. J Affect Disord. 2020;274:825–831.CrossRefGoogle ScholarPubMed
Chen, MH, Chang, WC, Bai, YM, et al. Cortico-thalamic dysconnection in early-stage schizophrenia: a functional connectivity magnetic resonance imaging study. Eur Arch Psychiatry Clin Neurosci. 2020;270(3):351–358.CrossRefGoogle ScholarPubMed
Siwek, M, Sowa-Kucma, M, Styczen, K, et al. Associations of serum cytokine receptor levels with melancholia, staging of illness, depressive and manic phases, and severity of depression in bipolar disorder. Mol Neurobiol. 2017;54(8):5883–5893.CrossRefGoogle ScholarPubMed
Goldstein, BI, Lotrich, F, Axelson, DA, et al. Inflammatory markers among adolescents and young adults with bipolar spectrum disorders. J Clin Psychiatry. 2015;76(11):1556–1563.CrossRefGoogle Scholar
Lin, K, Shao, R, Wang, R, et al. Inflammation, brain structure and cognition interrelations among individuals with differential risks for bipolar disorder. Brain Behav Immun. 2020;83:192–199.CrossRefGoogle ScholarPubMed
Stojanovic, A, Martorell, L, Montalvo, I, et al. Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology. 2014;41:23–32.CrossRefGoogle ScholarPubMed
Sowa-Kucma, M, Styczen, K, Siwek, M, et al. Are there differences in lipid peroxidation and immune biomarkers between major depression and bipolar disorder: effects of melancholia, atypical depression, severity of illness, episode number, suicidal ideation and prior suicide attempts. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:372–383.CrossRefGoogle ScholarPubMed
Misiak, B, Stanczykiewicz, B, Kotowicz, K, Rybakowski, JK, Samochowiec, J, Frydecka, D. Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: a systematic review. Schizophr Res. 2018;192:16–29.CrossRefGoogle ScholarPubMed
Roomruangwong, C, Noto, C, Kanchanatawan, B, et al. The role of aberrations in the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS) in different phenotypes of schizophrenia: the IRS-CIRS theory of schizophrenia. Mol Neurobiol. 2020;57(2):778–797.CrossRefGoogle ScholarPubMed
Radtke, FA, Chapman, G, Hall, J, Syed, YA. Modulating neuroinflammation to treat neuropsychiatric disorders. Biomed Res Int. 2017;2017:5071786.CrossRefGoogle ScholarPubMed
Hill, SK, Reilly, JL, Harris, MS, et al. A comparison of neuropsychological dysfunction in first-episode psychosis patients with unipolar depression, bipolar disorder, and schizophrenia. Schizophr Res. 2009;113(2–3):167–175.CrossRefGoogle ScholarPubMed
Bilder, RM, Goldman, RS, Robinson, D, et al. Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry. 2000;157(4):549–559.CrossRefGoogle ScholarPubMed
Reyes, AN, Cardoso, TA, Jansen, K, et al. Functional impairment and cognitive performance in mood disorders: a community sample of young adults. Psychiatry Res. 2017;251:85–89.CrossRefGoogle ScholarPubMed
Milton, DC, Ward, J, Ward, E, et al. The association between C-reactive protein, mood disorder, and cognitive function in UK Biobank. Eur Psychiatry. 2021;64(1):e14.CrossRefGoogle ScholarPubMed
Millett, CE, Perez-Rodriguez, M, Shanahan, M, et al. C-reactive protein is associated with cognitive performance in a large cohort of euthymic patients with bipolar disorder. Mol Psychiatry. 2019. doi:10.1038/s41380-019-0591-1.Google Scholar
Krogh, J, Benros, ME, Jorgensen, MB, Vesterager, L, Elfving, B, Nordentoft, M. The association between depressive symptoms, cognitive function, and inflammation in major depression. Brain Behav Immun. 2014;35:70–76.CrossRefGoogle ScholarPubMed
Baumeister, D, Ciufolini, S, Mondelli, V. Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment? Psychopharmacology (Berl). 2016;233(9):1575–1589.CrossRefGoogle ScholarPubMed
Stapel, B, Sieve, I, Falk, CS, Bleich, S, Hilfiker-Kleiner, D, Kahl, KG. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res. 2018;105:95–102.CrossRefGoogle ScholarPubMed
Wieck, A, Grassi-Oliveira, R, Prado, CH, et al. Pro-inflammatory cytokines and soluble receptors in response to acute psychosocial stress: differential reactivity in bipolar disorder. Neurosci Lett. 2014;580:17–21.CrossRefGoogle ScholarPubMed