Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-26T05:17:24.043Z Has data issue: false hasContentIssue false
  • English
  • Français

Association between increased serum interleukin-6 levels and sustained attention deficits in patients with major depressive disorder

Published online by Cambridge University Press:  08 February 2018

Gang Ye ,
Guang Zhong Yin ,
Zhen Tang ,
Jia Lin Fu ,
Jie Chen ,
Shan Shan Chen ,
Jia Li ,
Tian Fu ,
Xin Yu  and
Dong Wu Xu
...Show all authors
Gang Ye
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China
Guang Zhong Yin
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China
Zhen Tang
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China
Jia Lin Fu
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China
Jie Chen
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, PR China
Shan Shan Chen
Affiliation:
School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, PR China
Jia Li
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China
Tian Fu
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China
Xin Yu
Affiliation:
School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, PR China Institute of Mental Health, Peking University, Beijing 100083, PR China
Dong Wu Xu
Affiliation:
School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, PR China
Jeffrey K. Yao
Affiliation:
Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Li Hui*
Affiliation:
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, PR China
*
Author for correspondence: Li Hui, E-mail: huili004100@126.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines.

Objective

The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD.

Methods

Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays.

Results

There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (β = 0.31, t = 2.41, p = 0.025).

Conclusions

Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.

Keywords

Associationinterleukin-6major depressive disordersustained attention
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 15 , November 2018 , pp. 2508 - 2514
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Gang Ye, Guang Zhong Yin and Zhen Tang contributed equally to this work, and they should be regarded as joint first authors

References

Akiyama, K (1999) Serum levels of soluble IL-2 receptor α, IL-6 and IL-1 receptor antagonist in schizophrenia before and during neuroleptic administration. Schizophrenia Research 37, 97–106.Google Scholar
Anders, S, Tanaka, M and Kinney, DK (2013) Depression as an evolutionary strategy for defense against infection. Brain, Behavior, and Immunity 31, 9–22.Google Scholar
Borovcanin, M, Jovanovic, I, Radosavljevic, G, Djukic Dejanovic, S, Bankovic, D, Arsenijevic, N et al. (2012) Elevated serum level of type-2 cytokine and low IL-17 in first episode psychosis and schizophrenia in relapse. Journal of Psychiatric Research 46, 1421–1426.Google Scholar
Braw, Y, Aviram, S, Bloch, Y and Levkovitz, Y (2011) The effect of age on frontal lobe related cognitive functions of unmedicated depressed patients. Journal of Affective Disorders 129, 342–347.Google Scholar
Camp, NJ, Lowry, MR, Richards, RL, Plenk, AM, Carter, C, Hensel, CH et al. (2005) Genome-wide linkage analyses of extended Utah pedigrees identifies loci that influence recurrent, early-onset major depression and anxiety disorders. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 135B, 85–93.Google Scholar
Capuron, L, Gumnick, JF, Musselman, DL, Lawson, DH, Reemsnyder, A, Nemeroff, CB et al. (2002) Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 26, 643–652.Google Scholar
Capuron, L and Miller, AH (2011) Immune system to brain signaling: neuropsychoharmacological implications. Pharmacology & Therapeutics 130, 226–238.Google Scholar
Chocano-Bedoya, PO, Mirzaei, F, O'Reilly, EJ, Lucas, M, Okereke, OI, Hu, FB et al. (2014) C-reactive protein, interleukin-6, soluble tumor necrosis factor α receptor 2 and incident clinical depression. Journal of Affective Disorders 163, 25–32.Google Scholar
Cotrena, C, Branco, LD, Shansis, FM and Fonseca, RP (2016) Executive function impairments in depression and biopolar disorder: association with functional impairment and quality of life. Journal of Affective Disorders 190, 744–753.Google Scholar
Coull, JT, Frith, CD, Frackowiak, RS and Grasby, PM (1996) A fronto-parietal network for rapid visual information processing: a PET study of sustained attention and working memory. Neuropsychologia 34, 1085–1095.Google Scholar
Dahl, J, Ormstad, H, Aass, HC, Malt, UF, Bendz, LT, Sandvik, L et al. (2014) The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery. Psychoneuroendocriology 45, 77–86.Google Scholar
Danese, A, Moffitt, TE, Pariante, CM, Ambler, A, Poulton, R and Caspi, A (2008) Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Archives of General Psychiatry 65, 409–416.Google Scholar
Dantzer, R, O'Connor, JC, Freund, GG, Johnson, RW and Kelly, KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews Neuroscience 9, 46–56.Google Scholar
Di Nicola, M, Cattaneo, A, Hepgul, N, Di Forti, M, Aitchison, KJ, Janiri, L et al. (2012) Serum and gene expression profile of cytokines in first-episode psychosis. Brain, Behavior, and Immunity 31, 90–95.Google Scholar
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK et al. (2010) A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446–457.Google Scholar
Duivis, HE, de Jonge, P, Penninx, BW, Na, BY, Cohen, BE and Whooley, MA (2011) Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the heart and soul study. American Journal of Psychiatry 168, 913–920.Google Scholar
Felger, JC and Lotrich, FE (2013) Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 246, 199–229.Google Scholar
Frydecka, D, Misiak, B, Pawlak-Adamska, E, Karabon, L, Tomkiewicz, A, Sedlaczek, P et al. (2015) Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation. European Archives of Psychiatry and Clinical Neuroscience 265, 449–459.Google Scholar
Ganguli, R, Yang, Z, Shurin, G, Chengappa, KN, Brar, JS, Gubbi, AV et al. (1994) Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness. Psychiatry Research 51, 1–10.Google Scholar
Gimeno, D, Kivimäki, M, Brunner, EJ, Elovainio, M, De Vogli, R, Steptoe, A et al. (2009) Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychological Medicine 39, 413–423.Google Scholar
Gimeno, D, Marmot, MG and Singh-Manoux, A (2008) Inflammatory markers and cognitive function in middle-aged adults: the White-hall II study. Psychoneuroendocrinology 33, 1322–1334.Google Scholar
Goldsmith, DR, Rapaport, MH and Miller, BJ (2016) A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Molecular Psychiatry 21, 1696–1709.Google Scholar
Goodyer, IM (2015) Genes, environments and depression in young people. Archives of Disease in Childhood 100, 1064–1069.Google Scholar
Góra-Gebka, M, Liberek, A, Szydlowska-Lysiak, W, Bako, W and Korzon, M (2003) Serum interleukin 6 and interleukin 12 levels in children with chronic hepatitis HBV treated with interferon alpha. Annals of Hepatology 2, 92–97.Google Scholar
Grassi-Oliveira, R, Bauer, ME, Pezzi, JC, Teixeira, AL and Brietzke, E (2011) Interleukin-6 and verbal memory in recurrent major depressive disorder. Neuroendocrinology Letters 32, 540–544.Google Scholar
Heringa, SM, van den Berg, E, Reijmer, YD, Nijpels, G, Stehouwer, CD, Schalkwijk, CG et al. (2014) Markers of low-grade inflammation and endothelial dysfunction are related to reduced information processing speed and executive functioning in an older population-the Hoorn Study. Psychoneuroendocrinology 40, 108–118.Google Scholar
Hiles, SA, Baker, AL, de Malmanche, T and Attia, J (2012) Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis. Psychological Medicine 42, 2015–2026.Google Scholar
Howren, MB, Lamkin, DM and Suls, J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71, 171–186.Google Scholar
Jansen, R, Penninx, BW, Madar, V, Xia, K, Milaneschi, Y, Hottenga, JJ et al. (2016) Gene expression in major depressive disorder. Molecular Psychiatry 21, 444.Google Scholar
Jordanova, V, Stewart, R, Davies, E, Sherwood, R and Prince, M (2007) Markers of inflammation and cognitive decline in an African-Caribbean population. International Journal of Geriatric Psychiatry 22, 966–973.Google Scholar
Jung, J, Kang, J, Won, E, Nam, K, Lee, MS, Tae, WS et al. (2014) Impact of lingual gyrus volume on antidepressant response and neurocognitive functions in major depressive disorder: a voxel-based morphometry study. Journal of Affective Disorders 169, 179–187.Google Scholar
Kemp, AH, Hopkinson, PJ, Hermens, DF, Rowe, DL, Sumich, AL, Clark, CR et al. (2009) Fronto-temporal alterations within the first 200 ms during an attentional task distinguish major depression, non-clinical participants with depressed mood and healthy controls: a potential biomarker? Human Brain Mapping 30, 602–614.Google Scholar
Kern, S, Skoog, I, Bőrjesson-Hanson, A, Blennow, K, Zetterberg, H, Ostling, S et al. (2014) Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older women. Results from a population-based sample. Brain, Behavior, and Immunity 41, 55–58.Google Scholar
Khandaker, GM, Stochl, J, Zammit, S, Goodyer, I, Lewis, G and Jones, PB (2017) Childhood inflammatory markers and intelligence as predictors of subsequent persistent depressive symptoms: a longitudinal cohort study. Psychological Medicine 15, 1–12.Google Scholar
Kiecolt-Glaser, JK, Preacher, KL, MacCallum, RC, Atkinson, C, Malarkey, WB and Glaser, R (2003) Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proceedings of the National Academy of Sciences of the United States of America 100, 9090–9095.Google Scholar
Kopf, M, Baumann, H, Freer, G, Freudenberg, M, Lamers, M, Kishimoto, T et al. (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368, 339–342.Google Scholar
Kouwenhoven, M, Ozenci, V, Teleshova, N, Hussein, Y, Huang, YM, Eusebio, A et al. (2001) Enzyme-linked immunospot assays provide a sensitive tool for detection of cytokine secretion by monocytes. Clinical and Diagnostic Laboratory Immunology 8, 1248–1257.Google Scholar
Lee, RS, Hermens, DF, Porter, MA and Redoblado-Hodge, MA (2012) A meta-analysis of cognitive deficits in first-episode major depressive disorder. Journal of Affective Disorders 140, 113–124.Google Scholar
Lekander, M, von Essen, J, Schultzberg, M, Andreasson, AN, Garlind, A, Hansson, LO et al. (2011) Cytokines and memory across the mature life span of women. Scandinavian Journal of Psychology 52, 229–235.Google Scholar
Lezak, MD (1982) The problem of assessing executive functions. International Journal of Psychology 17, 281–297.Google Scholar
Li, CT, Lin, CP, Chou, KH, Chen, IY, Hsieh, JC, Wu, CL et al. (2010) Structural and cognitive deficits in remitting and non-remitting recurrent depression: a voxel-based morphometric study. NeuroImage 50, 347–356.Google Scholar
Liu, Y, Ho, RC and Mak, A (2012) Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. Journal of Affective Disorders 139, 230–239.Google Scholar
Loddick, SA, Turnbull, AV and Rothwell, NJ (1998) Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. Journal of Cerebral Blood Flow and Metabolism 18, 176–179.Google Scholar
Maalouf, FT, Brent, D, Clark, L, Tavitian, L, McHugh, RM, Sahakian, BJ et al. (2011) Neurocognitive impairment in adolescent major depressive disorder: State vs. Trait illness markers. Journal of Affective Disorders 133, 625–632.Google Scholar
Mann, DT, Williams, AM, Ward, P and Janelle, CM (2007) Perceptual-cognitive expertise in sport: a meta-analysis. Journal of Sport & Exercise Psychology 29, 457–478.Google Scholar
Marioni, RE, Strachan, MW, Reynolds, RW, Lowe, GD, Mitchell, RJ, Fowkes, FG et al. (2010) Association between raised inflammatory markers and cognitive decline in elderly people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes 59, 710–713.Google Scholar
Marsland, AL, Petersen, KL, Sathanoori, R, Muldoon, MF, Neumann, SA, Ryan, C et al. (2006) Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers. Psychosomatic Medicine 68, 895–903.Google Scholar
Mesulam, MM (1985) Principles of Behavioral Neurology. Philadelphia: Davis.Google Scholar
McDermott, LM and Ebmeier, KP (2009) A meta-analysis of depression severity and cognitive function. Journal of Affective Disorders 119, 1–8.Google Scholar
Milaneschi, Y, Corsi, AM, Penninx, BW, Bandinelli, S, Guralnik, JM and Ferrucci, L (2009) Interleukin-1 receptor antagonist and incident depressive symptoms over 6 years in older persons: the InCHIANTI study. Biological Psychiatry 65, 973–978.Google Scholar
Miller, AH, Maletic, V and Raison, CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 65, 732–741.Google Scholar
Mooijaart, SP, Sattar, N, Trompet, S, Lucke, J, Stott, DJ, Ford, I et al. (2013) Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study. Journal of Internal Medicine 274, 77–85.Google Scholar
Noto, C, Maes, M, Ota, VK, Teixeira, AL, Bressan, RA, Gadelha, A et al. (2015) High predictive value of immune-inflammatory biomarkers for schizophrenia diagnosis and association with treatment resistance. World Journal of Biological Psychiatry 27, 1–8.Google Scholar
Paelecke-Habermann, Y, Pohl, J and Leplow, B (2005) Attention and executive functions in remitted major depression patients. Journal of Affective Disorders 89, 125–135.Google Scholar
Paradiso, S, Lamberty, GJ, Garvey, MJ and Robinson, RG (1997) Cognitive impairment in the euthymic phase of chronic unipolar depression. Journal of Nervous and Mental Disease 185, 748–754.Google Scholar
Philips, MR, Zhang, J, Shi, Q, Song, Z, Ding, Z, Pang, S et al. (2009) Prevalence, treatment, and associated disability of mental disorders in four provinces in China during 2001–2005: an epidemiological survey. Lancet 373, 2041–2053.Google Scholar
Porter, RJ, Gallagher, P, Thompson, JM and Young, AH (2003) Neurocognitive impairment in drug-free patients with major depressive disorder. British Journal of Psychiatry 182, 214–220.Google Scholar
Rafnsson, SB, Deary, IJ, Smith, FB, Whiteman, MC, Rumley, A, Lowe, GD et al. (2007) Cognitive decline and markers of inflammation and hemostasis: the Edinburgh Artery Study. Journal of The American Geriatrics Society 55, 700–707.Google Scholar
Raison, CL, Rutherford, RE, Woolwine, BJ, Shuo, C, Schettler, P, Drake, DF et al. (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70, 31–41.Google Scholar
Rock, PL, Roiser, JP, Riedel, WJ and Blackwell, AD (2014) Cognitive impairment in depression: a systematic review and meta-analysis. Psychological Medicine 44, 2029–2040.Google Scholar
Sahakian, BJ and Owen, AM (1992) Computerized assessment in neuropsychiatry using CANTAB: discussion paper. Journal of The Royal Society Medicine 85, 399–402.Google Scholar
Setiawan, E, Wilson, AA, Mizrahi, R, Rusjan, PM, Miler, L, Rajkowska, G et al. (2015) Role of translocator protein density: a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry 72, 268–275.Google Scholar
Shao, TN, Yin, GZ, Yin, XL, Wu, JQ, Du, XD, Zhu, HL et al. (2017) Elevated triglyceride levels are associated with cognitive impairments among patients with major depressive disorder. Comprehensive Psychiatry 75, 103–109.Google Scholar
Simpson, EE, Hodkinson, CF, Maylor, EA, McCormack, JM, Rae, G, Strain, S et al. (2013) Intracellular cytokine production and cognition in healthy older adults. Psychoneuroendocrinology 38, 2196–2208.Google Scholar
Stewart, JC, Rand, KL, Muldoon, MF and Kamarck, TW (2009) A prospective evaluation of the directionality of the depression-inflammation relationship. Brain, Behavior, and Immunity 23, 936–944.Google Scholar
Tartter, M, Hammen, C, Bower, JE, Brennan, PA and Cole, S (2015) Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and IL1beta in youth. Brain, Behavior, and Immunity 46, 104–111.Google Scholar
Udina, M, Moreno-España, J, Navinés, D, Giménez, Z, Langohr, K, Gratacòs, M et al. (2013) Serotonin and interleukin-6: the role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms. Psychoneuroendocrinology 38, 1803–1813.Google Scholar
Upthegrove, R, Manzanares-Teson, N and Barnes, NM (2014) Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophrenia Research 155, 101–108.Google Scholar
van den Biggelaar, AH, Gussekloo, J, de Craen, AJ, Frölich, M, Stek, ML, van der Mast, RC et al. (2007) Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. Experimental Gerontology 42, 693–701.Google Scholar
van den Kommer, TN, Dik, MG, Comijs, HC, Jonker, C and Deeg, DJ (2010) Homocysteine and inflammation: predictors of cognitive decline in older persons? Neurobiology of Aging 31, 1700–1709.Google Scholar
van der Meere, J, Börger, N and van Os, T (2007) Sustained attention in major unipolar depression. Perceptual and Motor Skills 104, 1350–1354.Google Scholar
Wang, W, Bian, Q, Zhao, Y, Li, X, Wang, W, Du, J et al. (2014) Reliability and validity of the Chinese version of the Patients Health Questionaire (PHQ-9) in the general population. General Hospital Psychiatry 36, 539–544.Google Scholar
Williams, RA, Hagerty, BM, Cimprich, B, Therrien, B, Bay, E and Oe, H (2000) Changes in directed attention and short-term memory in depression. Journal of Psychiatric Research 34, 227–238.Google Scholar
Wright, CB, Sacco, RL, Rundek, T, Delman, J, Rabbani, L and Elkind, M (2006) Interleukin-6 is associated with cognitive function: the Northern Manhattan Study. Journal of Stroke & Cerebrovascular Diseases 15, 34–38.Google Scholar
Yang, X, Ma, X, Huang, B, Sun, G, Zhao, L, Lin, D et al. (2015) Gray matter volume abnormalities were associated with sustained attention in unmedicated major depression. Comprehensive Psychiatry 63, 71–79.Google Scholar
Yi, Z, Li, Z, Yu, S, Yuan, C, Hong, W, Wang, Z et al. (2012) Blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder. PLoS ONE 7, e31283.Google Scholar
Zhang, C, Wu, Z, Zhao, G, Wang, F and Fang, Y (2016) Identification of IL6 as a susceptibility gene for major depressive disorder. Scientific Reports 6, 31264.Google Scholar
Supplementary material: File

Ye et al. supplementary material

Table S1

Download Ye et al. supplementary material(File)
File 26.6 KB