Skip to main content
Top

Open Access 16-03-2024 | Suicide | Original Paper

Proinflammatory cytokine levels, cognitive function, and suicidal symptoms of adolescents and young adults with major depressive disorder

Authors: Mu-Hong Chen, Ya-Mei Bai, Ju-Wei Hsu, Kai-Lin Huang, Shih-Jen Tsai

Published in: European Archives of Psychiatry and Clinical Neuroscience

Login to get access

Abstract

Whether proinflammatory cytokine dysregulation and cognitive dysfunction are associated with suicidal symptoms in adolescents and young adults with major depressive disorder (MDD) remains uncertain. We assessed the cognitive function and proinflammatory cytokine levels of 43 and 51 patients aged 15–29 years with MDD and severe and mild suicidal symptoms, respectively, as well as those of 85 age- and sex-matched healthy controls. Specifically, we measured serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-2, and interleukin-6 and assessed cognitive function by using working memory and go/no-go tasks. The severity of the patients’ suicidal symptoms was based on Item 10 of the Montgomery–Åsberg Depression Rating Scale; scores of ≤ 2 and ≥ 4 indicated mild and severe symptoms, respectively. The patients with MDD and severe suicidal symptoms had higher levels of C-reactive protein (p = .019) and TNF-α (p = .002) than did the patients with mild symptoms or the healthy controls. The number of errors committed on the go/no-go by patients with MDD and severe suicidal symptoms (p = .001) was significantly higher than those by patients with MDD and mild symptoms or by controls. After adjusting for nonsuicidal depressive symptoms, we observed suicidal symptoms to be positively associated with TNF-α levels (p = .050) and errors on the go/no-go task (p = .021). Compared with mild suicidal symptoms, severe symptoms are associated with greater serum levels of proinflammatory cytokines and inferior cognitive function in adolescents and young adults with MDD.
Literature
1.
go back to reference Snowdon J, Chen YY, Zhong B, Yamauchi T (2018) A longitudinal comparison of age patterns and rates of suicide in Hong Kong, Taiwan and Japan and two Western countries. Asian J Psychiatry 31:15–20CrossRef Snowdon J, Chen YY, Zhong B, Yamauchi T (2018) A longitudinal comparison of age patterns and rates of suicide in Hong Kong, Taiwan and Japan and two Western countries. Asian J Psychiatry 31:15–20CrossRef
2.
go back to reference Chen YY, Yang CT, Pinkney E, Yip PSF (2021) The age-period-cohort trends of suicide in Hong Kong and Taiwan, 1979–2018. J Affect Disord 295:587–593CrossRefPubMed Chen YY, Yang CT, Pinkney E, Yip PSF (2021) The age-period-cohort trends of suicide in Hong Kong and Taiwan, 1979–2018. J Affect Disord 295:587–593CrossRefPubMed
4.
go back to reference Chang YH, Lin CY, Liao SC, Chen YY, Shaw FF, Hsu CY, Gunnell D, Chang SS (2023) Societal factors and psychological distress indicators associated with the recent rise in youth suicide in Taiwan: a time trend analysis. Aust N Z J Psychiatry 57:537–549CrossRefPubMed Chang YH, Lin CY, Liao SC, Chen YY, Shaw FF, Hsu CY, Gunnell D, Chang SS (2023) Societal factors and psychological distress indicators associated with the recent rise in youth suicide in Taiwan: a time trend analysis. Aust N Z J Psychiatry 57:537–549CrossRefPubMed
5.
go back to reference Chou CH, Ko HC, Wu JY, Cheng CP (2013) The prevalence of and psychosocial risks for suicide attempts in male and female college students in Taiwan. Suicide Life Threat Behav 43:185–197CrossRefPubMed Chou CH, Ko HC, Wu JY, Cheng CP (2013) The prevalence of and psychosocial risks for suicide attempts in male and female college students in Taiwan. Suicide Life Threat Behav 43:185–197CrossRefPubMed
6.
go back to reference Black C, Miller BJ (2015) Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. Biol Psychiatry 78:28–37CrossRefPubMed Black C, Miller BJ (2015) Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. Biol Psychiatry 78:28–37CrossRefPubMed
7.
go back to reference Gananca L, Oquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME (2016) The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinology 63:296–310CrossRefPubMed Gananca L, Oquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME (2016) The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinology 63:296–310CrossRefPubMed
8.
go back to reference O’Donovan A, Rush G, Hoatam G, Hughes BM, McCrohan A, Kelleher C, O’Farrelly C, Malone KM (2013) Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety 30:307–314CrossRefPubMed O’Donovan A, Rush G, Hoatam G, Hughes BM, McCrohan A, Kelleher C, O’Farrelly C, Malone KM (2013) Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety 30:307–314CrossRefPubMed
9.
go back to reference Mina VA, Lacerda-Pinheiro SF, Maia LC, Pinheiro RF Jr, Meireles CB, de Souza SI, Reis AO, Bianco B, Rolim ML (2015) The influence of inflammatory cytokines in physiopathology of suicidal behavior. J Affect Disord 172:219–230CrossRefPubMed Mina VA, Lacerda-Pinheiro SF, Maia LC, Pinheiro RF Jr, Meireles CB, de Souza SI, Reis AO, Bianco B, Rolim ML (2015) The influence of inflammatory cytokines in physiopathology of suicidal behavior. J Affect Disord 172:219–230CrossRefPubMed
10.
go back to reference Isung J, Aeinehband S, Mobarrez F, Nordstrom P, Runeson B, Asberg M, Piehl F, Jokinen J (2014) High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide. Transl Psychiatry 4:e470CrossRefPubMedPubMedCentral Isung J, Aeinehband S, Mobarrez F, Nordstrom P, Runeson B, Asberg M, Piehl F, Jokinen J (2014) High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide. Transl Psychiatry 4:e470CrossRefPubMedPubMedCentral
11.
go back to reference Lannoy S, Ohlsson H, Kendler KS, Sundquist J, Sundquist K, Edwards AC (2022) The causal effect of education and cognitive performance on risk for suicide attempt: a combined instrumental variable and co-relative approach in a Swedish national cohort. J Affect Disord 305:115–121CrossRefPubMedPubMedCentral Lannoy S, Ohlsson H, Kendler KS, Sundquist J, Sundquist K, Edwards AC (2022) The causal effect of education and cognitive performance on risk for suicide attempt: a combined instrumental variable and co-relative approach in a Swedish national cohort. J Affect Disord 305:115–121CrossRefPubMedPubMedCentral
12.
go back to reference Chen H, Hong L, Tong S, Li M, Sun S, Xu Y, Liu J, Feng T, Li Y, Lin G, Lu F, Cai Q, Xu D, Zhao K, Zheng T (2023) Cognitive impairment and factors influencing depression in adolescents with suicidal and self-injury behaviors: a cross-sectional study. BMC Psychiatry 23:247CrossRefPubMedPubMedCentral Chen H, Hong L, Tong S, Li M, Sun S, Xu Y, Liu J, Feng T, Li Y, Lin G, Lu F, Cai Q, Xu D, Zhao K, Zheng T (2023) Cognitive impairment and factors influencing depression in adolescents with suicidal and self-injury behaviors: a cross-sectional study. BMC Psychiatry 23:247CrossRefPubMedPubMedCentral
13.
go back to reference van Velzen LS, Toenders YJ, Avila-Parcet A, Dinga R, Rabinowitz JA, Campos AI, Jahanshad N, Renteria ME, Schmaal L (2022) Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study. Br J Psychiatry 220:210–218CrossRefPubMed van Velzen LS, Toenders YJ, Avila-Parcet A, Dinga R, Rabinowitz JA, Campos AI, Jahanshad N, Renteria ME, Schmaal L (2022) Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study. Br J Psychiatry 220:210–218CrossRefPubMed
14.
go back to reference Richard-Devantoy S, Berlim MT, Jollant F (2014) A meta-analysis of neuropsychological markers of vulnerability to suicidal behavior in mood disorders. Psychol Med 44:1663–1673CrossRefPubMed Richard-Devantoy S, Berlim MT, Jollant F (2014) A meta-analysis of neuropsychological markers of vulnerability to suicidal behavior in mood disorders. Psychol Med 44:1663–1673CrossRefPubMed
15.
go back to reference Montgomery SA (1980) Maprotiline, nomifensine, mianserin, zimelidine: a review of antidepressant efficacy in in-patients. Neuropharmacology 19:1185–1190CrossRefPubMed Montgomery SA (1980) Maprotiline, nomifensine, mianserin, zimelidine: a review of antidepressant efficacy in in-patients. Neuropharmacology 19:1185–1190CrossRefPubMed
16.
go back to reference Ballard ED, Luckenbaugh DA, Richards EM, Walls TL, Brutsche NE, Ameli R, Niciu MJ, Vande Voort JL, Zarate CA Jr (2015) Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant. J Psychiatr Res 68:68–73CrossRefPubMedPubMedCentral Ballard ED, Luckenbaugh DA, Richards EM, Walls TL, Brutsche NE, Ameli R, Niciu MJ, Vande Voort JL, Zarate CA Jr (2015) Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant. J Psychiatr Res 68:68–73CrossRefPubMedPubMedCentral
17.
go back to reference Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, Cheng CM, Su TP (2018) Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion. J Affect Disord 241:1–7CrossRefPubMed Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, Cheng CM, Su TP (2018) Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion. J Affect Disord 241:1–7CrossRefPubMed
18.
go back to reference Bai YM, Liu YL, Kuo HW, Tsai SJ, Hsu JW, Huang KL, Tu PC, Chen MH (2023) Procollagen type 1 N-terminal propeptide, neurofilament light chain, proinflammatory cytokines, and cognitive function in bipolar and major depressive disorders: an exploratory study of brain- bone axis and systemic inflammation. J Psychiatr Res 158:403–408CrossRefPubMed Bai YM, Liu YL, Kuo HW, Tsai SJ, Hsu JW, Huang KL, Tu PC, Chen MH (2023) Procollagen type 1 N-terminal propeptide, neurofilament light chain, proinflammatory cytokines, and cognitive function in bipolar and major depressive disorders: an exploratory study of brain- bone axis and systemic inflammation. J Psychiatr Res 158:403–408CrossRefPubMed
19.
go back to reference Pandey GN, Rizavi HS, Ren X, Fareed J, Hoppensteadt DA, Roberts RC, Conley RR, Dwivedi Y (2012) Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 46:57–63CrossRefPubMed Pandey GN, Rizavi HS, Ren X, Fareed J, Hoppensteadt DA, Roberts RC, Conley RR, Dwivedi Y (2012) Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 46:57–63CrossRefPubMed
20.
go back to reference Juengst SB, Kumar RG, Arenth PM, Wagner AK (2014) Exploratory associations with tumor necrosis factor-alpha, disinhibition and suicidal endorsement after traumatic brain injury. Brain Behav Immun 41:134–143CrossRefPubMed Juengst SB, Kumar RG, Arenth PM, Wagner AK (2014) Exploratory associations with tumor necrosis factor-alpha, disinhibition and suicidal endorsement after traumatic brain injury. Brain Behav Immun 41:134–143CrossRefPubMed
21.
go back to reference Melhem NM, Munroe S, Marsland A, Gray K, Brent D, Porta G, Douaihy A, Laudenslager ML, DePietro F, Diler R, Driscoll H, Gopalan P (2017) Blunted HPA axis activity prior to suicide attempt and increased inflammation in attempters. Psychoneuroendocrinology 77:284–294CrossRefPubMedPubMedCentral Melhem NM, Munroe S, Marsland A, Gray K, Brent D, Porta G, Douaihy A, Laudenslager ML, DePietro F, Diler R, Driscoll H, Gopalan P (2017) Blunted HPA axis activity prior to suicide attempt and increased inflammation in attempters. Psychoneuroendocrinology 77:284–294CrossRefPubMedPubMedCentral
22.
go back to reference Myers CE, Dave CV, Callahan M, Chesin MS, Keilp JG, Beck KD, Brenner LA, Goodman MS, Hazlett EA, Niculescu AB, St Hill L, Kline A, Stanley BH, Interian A (2022) Improving the prospective prediction of a near-term suicide attempt in veterans at risk for suicide, using a go/no-go task. Psychol Med 53(9):4245–4254CrossRefPubMedPubMedCentral Myers CE, Dave CV, Callahan M, Chesin MS, Keilp JG, Beck KD, Brenner LA, Goodman MS, Hazlett EA, Niculescu AB, St Hill L, Kline A, Stanley BH, Interian A (2022) Improving the prospective prediction of a near-term suicide attempt in veterans at risk for suicide, using a go/no-go task. Psychol Med 53(9):4245–4254CrossRefPubMedPubMedCentral
23.
24.
go back to reference Harfmann EJ, Rhyner KT, Ingram RE (2019) Cognitive inhibition and attentional biases in the affective go/no-go performance of depressed, suicidal populations. J Affect Disord 256:228–233CrossRefPubMed Harfmann EJ, Rhyner KT, Ingram RE (2019) Cognitive inhibition and attentional biases in the affective go/no-go performance of depressed, suicidal populations. J Affect Disord 256:228–233CrossRefPubMed
25.
go back to reference Huang MH, Chen MH, Hsu JW, Huang KL, Tsai SJ, Su TP, Bai YM (2022) Inflammation, cognitive dysfunction, and suicidal ideation among patients with major depression. CNS Spectr 27:724–730CrossRefPubMed Huang MH, Chen MH, Hsu JW, Huang KL, Tsai SJ, Su TP, Bai YM (2022) Inflammation, cognitive dysfunction, and suicidal ideation among patients with major depression. CNS Spectr 27:724–730CrossRefPubMed
26.
go back to reference Zelazny J, Melhem N, Porta G, Biernesser C, Keilp JG, Mann JJ, Oquendo MA, Stanley B, Brent DA (2019) Childhood maltreatment, neuropsychological function and suicidal behavior. J Child Psychol Psychiatry 60:1085–1093CrossRefPubMedPubMedCentral Zelazny J, Melhem N, Porta G, Biernesser C, Keilp JG, Mann JJ, Oquendo MA, Stanley B, Brent DA (2019) Childhood maltreatment, neuropsychological function and suicidal behavior. J Child Psychol Psychiatry 60:1085–1093CrossRefPubMedPubMedCentral
27.
go back to reference Zheng H, Webster MJ, Weickert CS, Beasley CL, Paulus MP, Yolken RH, Savitz J (2023) Cytomegalovirus antibodies are associated with mood disorders, suicide, markers of neuroinflammation, and microglia activation in postmortem brain samples. Mol Psychiatry Zheng H, Webster MJ, Weickert CS, Beasley CL, Paulus MP, Yolken RH, Savitz J (2023) Cytomegalovirus antibodies are associated with mood disorders, suicide, markers of neuroinflammation, and microglia activation in postmortem brain samples. Mol Psychiatry
28.
go back to reference de Andrade EG, Gonzalez Ibanez F, Tremblay ME (2022) Microglia as a hub for suicide neuropathology: future investigation and prevention targets. Front Cell Neurosci 16:839396CrossRef de Andrade EG, Gonzalez Ibanez F, Tremblay ME (2022) Microglia as a hub for suicide neuropathology: future investigation and prevention targets. Front Cell Neurosci 16:839396CrossRef
29.
go back to reference Brisch R, Wojtylak S, Saniotis A, Steiner J, Gos T, Kumaratilake J, Henneberg M, Wolf R (2022) The role of microglia in neuropsychiatric disorders and suicide. Eur Arch Psychiatry Clin Neurosci 272:929–945CrossRefPubMed Brisch R, Wojtylak S, Saniotis A, Steiner J, Gos T, Kumaratilake J, Henneberg M, Wolf R (2022) The role of microglia in neuropsychiatric disorders and suicide. Eur Arch Psychiatry Clin Neurosci 272:929–945CrossRefPubMed
30.
go back to reference Suzuki H, Ohgidani M, Kuwano N, Chretien F, de la Grandmaison GL, Onaya M, Tominaga I, Setoyama D, Kang D, Mimura M, Kanba S, Kato TA (2019) Suicide and microglia: recent findings and future perspectives based on human studies. Front Cell Neurosci 13:31CrossRefPubMedPubMedCentral Suzuki H, Ohgidani M, Kuwano N, Chretien F, de la Grandmaison GL, Onaya M, Tominaga I, Setoyama D, Kang D, Mimura M, Kanba S, Kato TA (2019) Suicide and microglia: recent findings and future perspectives based on human studies. Front Cell Neurosci 13:31CrossRefPubMedPubMedCentral
31.
go back to reference Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS (2018) Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: a positron emission tomography study. Biol Psychiatry 83:61–69CrossRefPubMed Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS (2018) Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: a positron emission tomography study. Biol Psychiatry 83:61–69CrossRefPubMed
Metadata
Title
Proinflammatory cytokine levels, cognitive function, and suicidal symptoms of adolescents and young adults with major depressive disorder
Authors
Mu-Hong Chen
Ya-Mei Bai
Ju-Wei Hsu
Kai-Lin Huang
Shih-Jen Tsai
Publication date
16-03-2024
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Psychiatry and Clinical Neuroscience
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-024-01780-5