Skip to main content

Advertisement

Log in

Inflammation in neurological and psychiatric diseases

  • Inflammation in acute and chronic neurological and psychiatric diseases
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

In recent years, compelling evidence suggests that inflammation plays a critical role in the pathology of a vast number of neurological diseases such as stroke, Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis as well as neuropsychiatric diseases such as major depression and schizophrenia. Despite emerging evidence in human and animal models alike, modulating inflammatory responses have yet to be proven as an effective treatment to prevent or delay the progression of these diseases. The primary focus of this special edition is to highlight some of our current findings on the complexities of targeting neuroinflammation as a novel therapy, and its role in neurological and psychiatric disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Akhondzadeh S, Tabatabaee M, Amini H, Ahmadi Abhari SA, Abbasi SH, Behnam B et al (2007) Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebo-controlled trial. Schizophr Res 90:179–185

    Article  PubMed  Google Scholar 

  • Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F (2007) Neuronal damage in brain inflammation. Arch Neurol 64(2):185–189

    Article  PubMed  Google Scholar 

  • Allan SM, Rothwell NJ (2003) Inflammation in central nervous system injury. Philos Trans R Soc Lond B Biol Sci 358(1438):1669–1677

    Article  PubMed  CAS  Google Scholar 

  • Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, Babulas VP, Susser ES (2004) Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatr 61:774–780

    Article  PubMed  Google Scholar 

  • Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Bernstein D, Yolken RH (2001) Maternal infections and subsequent psychosis among offspring. Arch Gen Psychiatry 58(11):1032–1037

    Article  PubMed  CAS  Google Scholar 

  • Capuron L, Fornwalt FB, Knight BT, Harvey PD, Ninan PT, Miller AH (2009) Does cytokine-induced depression differ from idiopathic major depression in medically healthy individuals? J Affect Disord 119(1–3):181–185

    Article  PubMed  CAS  Google Scholar 

  • Catena-Dell’Osso M, Bellantuono C, Consoli G, Baroni S, Rotella F, Marazziti D (2011) Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development? Curr Med Chem 18(2):245–255

    Article  PubMed  Google Scholar 

  • Chakraborty S, Kaushik DK, Gupta M, Basu A (2010) Inflammasome signaling at the heart of central nervous system pathology. J Neurosci Res 88(8):1615–1631

    PubMed  CAS  Google Scholar 

  • Creed F, Dickens C (2007) Depression in the medically ill. In: Steptoe A (ed) Depression and physical illness. Cambridge University Press, Cambridge, pp 3–18

    Google Scholar 

  • Członkowska A, Kurkowska-Jastrzębska I (2011) Inflammation and gliosis in neurological diseases—clinical implications. J Neuroimmunol 231(1–2):78–85

    Article  PubMed  Google Scholar 

  • Dantzer R, Kelley KW (2007) Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21:153–160

    Article  PubMed  CAS  Google Scholar 

  • Dhabhar FS, Burke HM, Epel ES, Mellon SH, Rosser R, Reus VI, Wolkowitz OM (2009) Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression. Psychiatr Res 43(11):962–969

    Article  Google Scholar 

  • Dickens C, McGowan L, Percival C, Tomenson B, Cotter L, Heagerty A, Creed F (2007) Depression is a risk factor for mortality after myocardial infarction: fact or artifact? J Am Coll Cardiol 49(18):1834–1840

    Article  PubMed  Google Scholar 

  • Dinan T (2008) Inflammatory markers in depression. Curr Opin Psychiatr 22:32–36

    Article  Google Scholar 

  • Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta analysis of cytokines in major depression. Biol Psychiatry 67(5):446–57

    Google Scholar 

  • Downes CE, Crack PJ (2010) Neural injury following stroke: are Toll-like receptors the link between the immune system and the CNS? Br J Pharmacol 160(8):1872–1888

    PubMed  CAS  Google Scholar 

  • Dunn AJ (2008) The cytokines and depression hypothesis: an update. Neuroimmune Biol 6:485–506

    Article  CAS  Google Scholar 

  • Emerich DF, Dean RL 3rd, Bartus RT (2002) The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct? Exp Neurol 173(1):168–181

    Article  PubMed  Google Scholar 

  • Ferretti MT, Cuello AC (2011) Does a pro-inflammatory process precede Alzheimer’s disease and mild cognitive impairment? Curr Alzheimer Res 8(2):164–174

    PubMed  CAS  Google Scholar 

  • Fuller S, Steele M, Münch G (2010) Activated astroglia during chronic inflammation in Alzheimer’s disease—do they neglect their neurosupportive roles? Mutat Res 690(1–2):40–49

    PubMed  CAS  Google Scholar 

  • Gattaz WF, Abrahao AL, Foccaccia R (2004) Childhood meningitis, brain maturation and the risk of schizophrenia. Eur Arch Psychiatry Clin Neurosci 254:23–26

    Article  PubMed  Google Scholar 

  • Glassman AH, Miller GE (2007) Where there is depression, there is inflammation… sometimes! Biol Psychiatry 62:280–281

    Article  PubMed  Google Scholar 

  • Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, Yirmiya R (2008) Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13(7):717–728

    Article  PubMed  CAS  Google Scholar 

  • Griffiths M, Neal JW, Gasque P (2007) Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins. Int Rev Neurobiol 82:29–55

    Article  PubMed  CAS  Google Scholar 

  • Hanson DR, Gottesman II (2005) Theories of schizophrenia: a genetic-inflammatory-vascular synthesis. BMC Med Genet 6:7

    Article  PubMed  Google Scholar 

  • Heneka MT (2006) Inflammation in Alzheimer’s disease. J Clin Neurosci Res 6:247–260

    Article  CAS  Google Scholar 

  • Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8(4):382–397

    Article  PubMed  CAS  Google Scholar 

  • Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186

    Article  PubMed  CAS  Google Scholar 

  • Huang Y, Henry CJ, Dantzer R, Johnson RW, Godbout JP (2008) Exaggerated sickness behavior and brain proinflammatory cytokine expression in aged mice in response to intracerebroventricular lipopolysaccharide. Neurobiol Aging 29(11):1744–1753

    Article  PubMed  CAS  Google Scholar 

  • Iadecola C, Anrather J (2011) The immunology of stroke: from mechanisms to translation. Nat Med 17(7):796–808

    Article  PubMed  CAS  Google Scholar 

  • Jin R, Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87(5):779–789

    Google Scholar 

  • Keeley P, Creed F, Tomenson B, Todd C, Borglin G, Dickens C (2008) Psychosocial predictors of health-related quality of life and health service utilisation in people with chronic low back pain. Pain 135(1–2):142–150

    Article  PubMed  Google Scholar 

  • Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91(2):461–553

    Article  PubMed  CAS  Google Scholar 

  • Khandelwal PJ, Herman AM, Moussa CE (2011) Inflammation in the early stages of neurodegenerative pathology. J Neuroimmunol 238(1–2):1–11

    Article  PubMed  CAS  Google Scholar 

  • Kim K, Lee SG, Kegelman TP, Su ZZ, Das SK, Dash R, Dasgupta S, Barral PM, Hedvat M, Diaz P, Reed JC, Stebbins JL, Pellecchia M, Sarkar D, Fisher PB (2011) Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol 226(10):2484–2493

    Article  PubMed  CAS  Google Scholar 

  • Körschenhausen DA, Hampel HJ, Ackenheil M, Penning R, Müller N (1996) Fibrin degradation products in post mortem brain tissue of schizophrenics: a possible marker for underlying inflammatory processes. Schizophr Res 19(2–3):103–109

    Article  PubMed  Google Scholar 

  • Lucas SM, Rothwell NJ, Gibson RM (2006) The role of inflammation in CNS injury and disease. Br J Pharmacol 147(Suppl 1):S232–S240

    PubMed  CAS  Google Scholar 

  • Machado A, Herrera AJ, Venero JL, Santiago M, De Pablos RM, Villarán RF, Espinosa-Oliva AM, Argüelles S, Sarmiento M, Delgado-Cortés MJ, Mauriño R, Cano J (2011) Peripheral inflammation increases the damage in animal models of nigrostriatal dopaminergic neurodegeneration: possible implication in Parkinson’s disease incidence. Parkinsons Dis 2011:0393769

  • Markiewicz I, Lukomska B (2006) The role of astrocytes in the physiology and pathology of the central nervous system. Acta Neurobiol Exp (Wars) 66(4):343–358

    Google Scholar 

  • Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741

    Article  PubMed  CAS  Google Scholar 

  • Mogi M, Harada M, Narabayashi H, Inagaki H, Minami M, Nagatsu T (1996) Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson’s disease. Neurosci Lett 211(1):13–16

    Article  PubMed  CAS  Google Scholar 

  • Müller N (2010) COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence. Curr Opin Invest Drugs 11:31–42

    Google Scholar 

  • Müller N, Schwarz MJ (2007) The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol Psychiatry 12:988–1000

    Article  PubMed  Google Scholar 

  • Müller N, Schwarz MJ (2008) A psychoneuroimmunological perspective to Emil Kraepelins dichotomy. Schizophrenia and major depression as inflammatory CNS disorders. Eur Arch Psychiatry Clin Neurosci 258((Suppl. 2)):97–106

    Article  PubMed  Google Scholar 

  • Müller N, Ulmschneider M, Scheppach C, Schwarz MJ, Ackenheil M, Möller HJ, Gruber R, Riedel M (2004a) COX-2 inhibition as a treatment approach in schizophrenia: immunological considerations and clinical effects of celecoxib add-on therapy. Eur Arch Psychiatry Clin Neurosci 254(1):14–22

    Article  PubMed  Google Scholar 

  • Müller N, Riedel M, Dehning S, Spellmann I, Müller-Arends A, Cerovecki A et al (2004b) Is the therapeutic effect of celecoxib in schizophrenia depending from duration of disease? Neuropsychopharmacology 29:176

  • Müller N, Riedel M, Schwarz MJ, Engel RR (2005) Clinical effects of COX-2 inhibitors on cognition in schizophrenia. Eur Arch Psychiatry Clin Neurosci 255(2):149–151

    Article  PubMed  Google Scholar 

  • Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Müller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Möller HJ, Arolt V, Riedel M (2006) The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 11(7):680–684

    Article  PubMed  Google Scholar 

  • Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS, Greiner K, Nemeroff CB, Miller AH (2001) Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 344(13):961–966

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Cytokines in Parkinson’s disease. J Neural Transm Suppl 58:143–151

    PubMed  Google Scholar 

  • Palin K, Bluthé RM, McCusker RH, Moos F, Dantzer R, Kelley KW (2007) TNFalpha-induced sickness behavior in mice with functional 55 kD TNF receptors is blocked by central IGF-I. J Neuroimmunol 187(1–2):55–60

    Article  PubMed  CAS  Google Scholar 

  • Perry VH, Nicoll JA, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6(4):193–201

    Article  PubMed  Google Scholar 

  • Raedler TJ (2011) Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatry 24:519–525

    PubMed  Google Scholar 

  • Raison CL, Capuron L, Miller AH (2006) Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 27:24–31

    Article  PubMed  CAS  Google Scholar 

  • Ransohoff RM, Perry VH (2009) Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27:119–145

    Article  PubMed  CAS  Google Scholar 

  • Rook GA, Lowry CA (2008) The hygiene hypothesis and psychiatric disorders. Trends Immunol 29:150–158

    Article  PubMed  CAS  Google Scholar 

  • Sharpley CF, Agnew LL (2011) Cytokines and depression: findings, issues, and treatment implications. Rev Neurosci 22:295–302

    Article  PubMed  Google Scholar 

  • Skaper SD (2007) The brain as a target for inflammatory processes and neuroprotective strategies. Ann N Y Acad Sci 1122:23–34

    Article  PubMed  CAS  Google Scholar 

  • Smith JA, Das A, Ray SK, Banik NL (2012) Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull 87:10–20

    Article  PubMed  CAS  Google Scholar 

  • Sofroniew MV (2005) Reactive astrocytes in neural repair and protection. Neuroscientist 11(5):400–407

    Article  PubMed  CAS  Google Scholar 

  • Stone EA, Lin Y, Quartermain D (2008) A final common pathway for depression? Progress toward a general conceptual framework. Neurosci Biobehav Rev 32:508–524

    Article  PubMed  Google Scholar 

  • Streit WJ, Mrak RE, Griffin WS (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation 30:14

    Article  Google Scholar 

  • Wang DD, Bordey A (2008) The astrocyte odyssey. Prog Neurobiol 86(4):342–367

    PubMed  CAS  Google Scholar 

  • Wang Q, Tang XN, Yenari MA (2007) The inflammatory response in stroke. J Neuroimmunol 184(1–2):53–68

    Article  PubMed  CAS  Google Scholar 

  • Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P (2011) Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci USA 108(22):9262–9267

    Article  PubMed  CAS  Google Scholar 

  • Wee YV (2010) Inflammation in neurological disorders: a help or a hindrance? Neuroscientist 16(4):408–420

    Article  Google Scholar 

  • WHO (2001) Cross-national comparisons of the prevalences and correlates of mental disorders, WHO international consortium in psychiatric epidemiology. World Health Organ 78:413–426

    Google Scholar 

  • Wood PL (1995) Microglia as a unique cellular target in the treatment of stroke: potential neurotoxic mediators produced by activated microglia. Neurol Res 17(4):242–248

    PubMed  CAS  Google Scholar 

  • Yang Y, Rosenberg GA (2011) Blood–brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 42(11):3323–3328

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Rempe DA (2010) Targeting astrocytes for stroke therapy. Neurotherapeutics 7(4):439–451

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Parto S. Khansari.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khansari, P.S., Sperlagh, B. Inflammation in neurological and psychiatric diseases. Inflammopharmacol 20, 103–107 (2012). https://doi.org/10.1007/s10787-012-0124-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-012-0124-x

Keywords

Navigation