Skip to main content Accessibility help
Hostname: page-component-846f6c7c4f-whwnh Total loading time: 1.083 Render date: 2022-07-07T17:21:53.853Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true
Bipolar Disorders Bipolar Disorders
Basic Mechanisms and Therapeutic Implications
Buy print or eBook[Opens in a new window]

21 - Immune dysregulation in bipolar disorder

Published online by Cambridge University Press:  05 May 2016

Jair C. Soares
University of Texas Health Science Center, Houston
Allan H. Young
King's College London
Get access


Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Bipolar Disorders
Basic Mechanisms and Therapeutic Implications
, pp. 269 - 285
Publisher: Cambridge University Press
Print publication year: 2016

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.)


Altamura, A.C., Mundo, E., Cattaneo, E., et al. The MCP-1 gene (SCYA2) and mood disorders: preliminary results of a case control association study. NeuroImmunoModulation. 2010;17:126–31.CrossRefGoogle ScholarPubMed
Anisman, H. Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci. 2009;34(1):420.Google ScholarPubMed
Austin, M., Tan, Y. C. J. Mania associated with infliximab. Aust N Z J Psychiatry. 2012;46(7):684–5.CrossRefGoogle ScholarPubMed
Bachen, E.A., Chesney, M.A., Criswell, L.A. Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthr Rheum. 2009;61:822–9.CrossRefGoogle ScholarPubMed
Bai, Y.M., Su, T.P., Tsai, S.J., et al. Comparison of inflammatory cytokine levels among type I / type II and manic/hypomanic/euthymic/depressive states of bipolar disorder. J Affect Disord. 2014;166:187–92.CrossRefGoogle ScholarPubMed
Barbosa, I.G., Rocha, N.P., de Miranda, A.S., et al. Increased levels of adipokines in bipolar disorder. J Psychiatric Res. 2012;46(3):389–93.CrossRefGoogle ScholarPubMed
Barbosa, I. G., Rocha, N. P., Bauer, M. E., et al. Chemokines in bipolar disorder: trait or state? Eur Arch Psychiatry Clin Neurosci. 2013a;263:159–65.Google ScholarPubMed
Barbosa, I.G., Rocha, N.P., Huguet, R.B., et al. Executive dysfunction in euthymic bipolar disorder patients and its association with plasma biomarkers. J Affect Disord. 2013b;137:151–5.Google ScholarPubMed
Barbosa, I.G., Nogueira, C.R., Rocha, N.P., et al. Altered intracellular signaling cascades in peripheral blood mononuclear cells from BD patients. J Psychiatr Res. 2013c;47(12):1949–54.CrossRefGoogle ScholarPubMed
Barbosa, I.G., Rocha, N.P., Assis, F., et al. Monocyte and lymphocyte activation in bipolar disorder: a new piece in the puzzle of immune dysfunction in mood disorders. Int J Neuropsychopharmacol. 2014;18(1):pii: pyu021.Google ScholarPubMed
Becking, K., Boschloo, L., Vogelzangs, N., et al. The association between immune activation and manic symptoms in patients with a depressive disorder. Transl Psychiatry. 2013;22:e314.CrossRefGoogle Scholar
Berk, M. Neuroprogression: pathways to progressive brain changes in bipolar disorder. Int J Neuropsychopharmacol. 2009;12(4):441–5.CrossRefGoogle Scholar
Berk, M., Kapczinski, F., Andreazza, A. C., et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2009;35(3):804–17.Google ScholarPubMed
Bezchlibnyk, Y. B., Wang, J.F., McQueen, G. M., et al. Gene expression differences in bipolar disorder revealed by cDNA array analysis of postmortem frontal cortex. J Neurochem. 2001;79(4):826–34.Google Scholar
Bluestone, J.A., Abbas, A.K. Natural versus adaptive regulatory T cells. Nat Rev Immunol. 2003;3:253–7.CrossRefGoogle ScholarPubMed
Boufidou, F., Nikolaou, C., Alevizos, B., et al. Cytokine production in bipolar affective disorder patients under lithium treatment. J Affect Disord. 2004;82:309–13.CrossRefGoogle ScholarPubMed
Breunis, M.N., Kupka, R.W., Nolen, W.A., et al. High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder. Biol Psychiatry. 2003;53:157–65.CrossRefGoogle ScholarPubMed
Brietzke, E., Lafer, B. Induction of manic switch by the tumour necrosis factor-α antagonist infliximab. Psychiatry Clin Neurosci. 2010;64(4):442–3.Google Scholar
Brietzke, E., Kauer-Sant’Anna, M., Teixeira, A. L., et al. Abnormalities in serum chemokine levels in euthymic patients with bipolar disorder. Brain Behav Immun. 2009;23:1079–82.CrossRefGoogle ScholarPubMed
BrooksIII, J. O., Wang, P. W., Bonner, J. C., et al. Decreased prefrontal, anterior cingulate, insula, and ventral striatal metabolism in medication-free depressed outpatients with bipolar disorder. J Psychiatric Res. 2009;43(3):181–8.CrossRefGoogle Scholar
Brown, N.C., Andreazza, A.C., Young, L.T. An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res. 2014;218(12):61–8.CrossRefGoogle Scholar
Bull, S.J., Huezo-Diaz, P., Binder, E.B., et al. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry. 2009;14(12):1145.CrossRefGoogle Scholar
Cacci, E., Claasen, J.H., Kokaia, Z. Microglia-derived tumor necrosis factor-α exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res. 2005;80(6):789–97.CrossRefGoogle ScholarPubMed
Chen, D.T., Jiang, X., Akula, N., et al. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder. Mol Psychiatry. 2013;18(2):195205.CrossRefGoogle ScholarPubMed
Chung, K.H., Huang, S.H., Wu, J.Y., et al. The link between high-sensitivity C-reactive protein and orbitofrontal cortex in euthymic bipolar disorder. Neuropsychobiology. 2013;68(3):168–73.CrossRefGoogle ScholarPubMed
Clerici, M., Arosio, B., Mundo, E, et al. Cytokine polymorphisms in the pathophysiology of mood disorders. CNS Spectrums. 2009;14(8):419–25.CrossRefGoogle ScholarPubMed
Contreras, M. Libro de la Melancholía by Andrés Velázquez (1585). Part 1. The intellectual origins of the book. Hist Psychiatry. 2003;14:2540.Google Scholar
Dantzer, R. Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci. 2001;933:222–34.Google ScholarPubMed
Darko, D.F., Rose, J., Gillin, J.C., et al. Neutrophilia and lymphopenia in major mood disorders. Psychiatry Res. 1988;25(3):243–51.CrossRefGoogle Scholar
Dean, B., Gibbons, A. S., Tawadros, N., et al. Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders. Mol Psychiatry. 2013;18(7):767–73.CrossRefGoogle ScholarPubMed
Degner, D., Haust, M., Meller, J., et al. Association between autoimmune thyroiditis and depressive disorder in psychiatric outpatients. Eur Arch Psychiatry Clin Neurosci. 2015;265(1):6772.CrossRefGoogle ScholarPubMed
Dickerson, F., Stallings, C., Origoni, A., et al. Markers of gluten sensitivity and celiac disease in bipolar disorder. Bipolar Disord. 2011;13(1):52–8.CrossRefGoogle Scholar
Dickerson, F., Stallings, C., Origoni, A., et al. Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder. J Affect Disord. 2013;5;150(2):456–9.Google Scholar
Diniz, B.S., Teixeira, A.L., Talib, L., et al. Interleukin-1beta serum levels is increased in antidepressant-free elderly depressed patients. Am J Geriatr Psychiatry. 2010;18(2):172–6.CrossRefGoogle Scholar
Doganavsargil-Baysal, O. B., Cinemre, B., Aksoy, U.M., et al. Levels of TNF-α, soluble TNF receptors (sTNFR1, sTNFR2), and cognition in bipolar disorder. Hum Psychopharmacol. 2013;28(2):160–7.CrossRefGoogle Scholar
do Prado, C.H., Rizzo, L.B., Wieck, A., et al. Reduced regulatory T cells are associated with higher levels of Th1/TH17 cytokines and activated MAPK in type 1 bipolar disorder. Psychoneuroendocrinology. 2013;38:667–76.CrossRefGoogle ScholarPubMed
Drexhage, R.C., Hoogenboezem, T.H., Versnel, M.A., et al. The activation of monocyte and T cell networks in patients with bipolar disorder. Brain Behav Immun. 2011;25:1206–13.CrossRefGoogle Scholar
Eaton, W.W., Pedersen, M.G., Nielsen, P.R., et al. Autoimmune diseases, bipolar disorder, and non-affective psychosis. Bipolar Disord. 2010;12(6):638–46.CrossRefGoogle ScholarPubMed
Edwards, L.J., Constantinescu, C.S. A prospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic. Mult Scler. 2004;10:575–81.CrossRefGoogle Scholar
El-Sayed, A.A., Ramy, H.A. Immunological changes in patients with mania: changes in cell mediated immunity in a sample from Egyptian patients. Egypt J Immunol. 2006;13(1):7985.Google Scholar
Fava, G.A., Kellner, R. Staging: a neglected dimension in psychiatric classification. Acta Psychiatr Scand. 1993;87(4):225–30.CrossRefGoogle ScholarPubMed
Fond, G., Hamdani, N., Kapczinski, F., et al. Effectiveness and tolerance of anti-inflammatory drugs’ add-on therapy in major mental disorders: a systematic qualitative review. Acta Psychiatr Scand. 2014;129(3):163–79.CrossRefGoogle Scholar
Frank, E., Nimgaonkar, V.L., Phillips, M.L., et al. All the world’s a (clinical) stage: rethinking bipolar disorder from a longitudinal perspective. Mol Psychiatry. 2015;20(1):2331.CrossRefGoogle ScholarPubMed
Gildengers, A. G., Chung, K.H., Huang, S. H., et al. Neuroprogressive effects of lifetime illness duration in older adults with bipolar disorder. Bipolar Disord. 2014;16(6):617–23.CrossRefGoogle ScholarPubMed
Gilroy, D.W., Lawrence, T., Perretti, M., et al. Inflammatory resolution: new opportunities for drug discovery Nat Rev Drug Disc. 2004;3:401–16.CrossRefGoogle ScholarPubMed
Grassi-Oliveira, R., Brietzke, E., Pezzi, J.C., et al. Increased soluble tumor necrosis factor-alpha receptors in patients with major depressive disorder. Psychiatry Clin Neurosci. 2009;63(2):202–8.CrossRefGoogle ScholarPubMed
Haarman, B.C., Riemersma-Van der Lek, R.F., Burger, H., et al. Relationship between clinical features and inflammation-related monocyte gene expression in bipolar disorder – towards a better understanding of psychoimmunological interactions. Bipolar Disord. 2014a;16(2):137–50.Google ScholarPubMed
Haarman, B.C., Riemersma-Van der Lek, R.F., de Groot, J.C., et al. Neuroinflammation in bipolar disorder – A [(11)C]-(R)-PK11195 positron emission tomography study. Brain Behav Immun. 2014b;40:219–25.Google Scholar
Hacker, U.T., Erhardt, S., Tschoep, K., et al. Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1β after live yellow fever vaccination. Clin Exp Immunol. 2001;125:465–9.CrossRefGoogle ScholarPubMed
Hamdani, N., Doukhan, R., Kurtlucan, O., et al. Immunity, inflammation, and bipolar disorder: diagnostic and therapeutic implications. Curr Psychiatry Rep. 2013;15(9):387.CrossRefGoogle ScholarPubMed
Hillegers, M.H., Reichart, C.G., Wals, M., et al. Signs of a higher prevalence of autoimmune thyroiditis in female offspring of bipolar parents. Eur Neuropsychopharmacol. 2007;17:394–9.CrossRefGoogle ScholarPubMed
Himmerich, H., Bartsch, S., Hamer, H., et al. Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro. J Psychiatry Res. 2013;47(11):1751–9.CrossRefGoogle ScholarPubMed
Himmerich, H. Bartsch, S., Hamer, H., et al. Modulation of cytokine production by drugs with antiepileptic or mood stabilizer properties in anti-CD3- and anti-CD40-stimulated blood in vitro. Oxidat Med Cell Longevity. 2014;2014:806162.CrossRefGoogle ScholarPubMed
Hope, S., Melle, I., Aukrust, P., et al. Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor. Bipolar Disord. 2009;11(7):726–34.CrossRefGoogle ScholarPubMed
Hope, S., Dieset, I., Agartz, I., et al. Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia. J Psychiatr Res. 2011;45:1608–16.CrossRefGoogle ScholarPubMed
Hope, S., Ueland, T., Steen, N.E., et al. Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder. Schizophr Res. 2013;145(13):3642.CrossRefGoogle ScholarPubMed
Howren, M.B., Lamkin, D.M., Suls, J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomat Med. 2009;71(2):171–86.CrossRefGoogle Scholar
Hsu, J.W., Lirng, J.F., Wang, S.J., et al. Association of thalamic serotonin transporter and interleukin-10 in bipolar I disorder: a SPECT study. Bipolar Disord. 2014;16(3):241–8.CrossRefGoogle Scholar
Huang, J., Perlis, R.H., Lee, P.H., et al. Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression. Am JPsychiatry. 2010;167(10):1254–63.Google ScholarPubMed
Hung, Y.J., Hsieh, C.H., Chen, Y.J., et al. Insulin sensitivity, proinflammatory markers and adiponectin in young males with different subtypes of depressive disorder. Clin Endocrinol. 2007;67:784–9.CrossRefGoogle Scholar
Isgren, A., Jakobsson, J., Pålsson, E., et al. Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment. Brain Behav Immun. 2015;43:198204.CrossRefGoogle ScholarPubMed
Johansson, A.S., Owe-Larsson, B., Asp, L., et al. Activation of kynurenine pathway in ex vivo fibroblasts from patients with bipolar disorder or schizophrenia: cytokine challenge increases production of 3-hydroxykynurenine. J Psychiatry Res. 2013;47(11):1815–23.CrossRefGoogle ScholarPubMed
Kaufman, K. R. Etanercept, anticytokines and mania. Int Clin Psychopharmacol. 2005;20(4):239–41.CrossRefGoogle ScholarPubMed
Kesebir, S., Turan, C., Süner, O., et al. Increased ICAM, VCAM, and E-selectin levels in first manic episode. Bipolar Disord. 2014 (in press) doi: 10.1111/bdi.12269.Google Scholar
Kim, Y.K., Suh, I.B., Kim, H., et al. The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: effects of psychotropic drugs. Mol Psychiatry. 2002;7:1107–14.CrossRefGoogle ScholarPubMed
Kim, Y. K., Jung, H.G., Myint, A.M., et al. Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord. 2007;104:91–5.CrossRefGoogle ScholarPubMed
Knijff, E.M., Ruwhof, C., de Wit, H.J., et al. Monocyte-derived dendritic cells in bipolar disorder. Biol Psychiatry. 2006;59:317–26.CrossRefGoogle ScholarPubMed
Knijff, E.M., Breunis, M.N., Kupka, R.W., et al. An imbalance in the production of IL-1beta and IL-6 by monocytes of bipolar patients: restoration by lithium treatment. Bipolar Disord. 2007;9:743–53.CrossRefGoogle ScholarPubMed
Kunz, M., Ceresér, K.M., Goi, P.D., et al. Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance. Rev Brasil Psiquiatr. 2011;33(3):268–74.Google ScholarPubMed
Kupferschmidt, D. A., Zakzanis, K. K. Toward a functional neuroanatomical signature of bipolar disorder: quantitative evidence from the neuroimaging literature. Psychiatry Res Neuroimaging 2011;193(2):71–9.CrossRefGoogle Scholar
Kupka, R.W., Nolen, W.A., Post, R.M., et al. High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure. Biol Psychiatry. 2002;51:305–11.CrossRefGoogle ScholarPubMed
Lana-Peixoto, M.A., Teixeira, A.L. Jr., Haase, V.G. Interferon beta-1ª-iduced depression and suicidal ideation in multiple sclerosis. Arquivos Neuropsiquiatria. 2002;60(3-B):721–4.CrossRefGoogle ScholarPubMed
Langan, C., McDonald, C. Neurobiological trait abnormalities in bipolar disorder. Mol Psychiatry. 2009;14(9):833–46.CrossRefGoogle ScholarPubMed
Levine, J., Barak, Y., Chengappa, K.N., et al. Cerebrospinal cytokine levels in patients with acute depression. Neuropsychobiology. 1999;40(4):171–6.CrossRefGoogle ScholarPubMed
Liu, H.C., Yang, Y.Y., Chou, Y.M., et al. Immunologic variables in acute mania of bipolar disorder. J Neuroimmunol. 2004;150(12):116–22.CrossRefGoogle Scholar
López-Jaramillo, C., Lopera-Vásquez, J., Gallo, A., et al. Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Bipolar Disord. 2010;12(5):557–67.CrossRefGoogle ScholarPubMed
Lotrich, F.E., Rabinovitz, M., Gironda, P., et al. Depression following pegylated interferon-alpha: characteristics and vulnerability. J Psychosom Res. 2007;63:131–5.CrossRefGoogle Scholar
Maddock, C., Landau, S., Barry, K., et al. Psychopathological symptoms during interferon-alpha and ribavirin treatment: effects on virologic response. Mol Psychiatry. 2005;10(4):332–3.CrossRefGoogle ScholarPubMed
Maes, M., Yirmyia, R., Noraberg, J., et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009;24:2753.CrossRefGoogle ScholarPubMed
McGorry, P.D., Hickie, I.B., Yung, A.R., et al. Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry. 2006;40:616–22.CrossRefGoogle ScholarPubMed
McGuffin, P., Rijsdijk, F., Andrew, M., et al. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry. 2003;60(5):497502.CrossRefGoogle ScholarPubMed
Medzhitov, R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140:771–6.CrossRefGoogle ScholarPubMed
Meira-Lima, I.V., Pereira, A.C., Mota, G.F., et al. Analysis of a polymorphism in the promoter region of the tumor necrosis factor alpha gene in schizophrenia and bipolar disorder: further support for an association with schizophrenia. Mol Psychiatry. 2003;8:718–20.CrossRefGoogle ScholarPubMed
Middle, F., Jones, I., Robertson, E., et al. Tumour necrosis factor α and bipolar affective puerperal psychosis. Psychiatr Genet. 2000;10:195–8.CrossRefGoogle ScholarPubMed
Miller, C., Bauer, M.S. Excess mortality in bipolar disorders. Curr Psychiatry Rep. 2014;16(11):499.CrossRefGoogle Scholar
Modabbernia, A., Taslimi, S., Brietzke, E., et al. Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol Psychiatry. 2013;74(1):1525.CrossRefGoogle ScholarPubMed
Mota, R., Gazal, M., Acosta, B. A., et al. Interleukin-1β is associated with depressive episode in major depression but not in bipolar disorder. J Psychiatr Res. 2013;47:2011–14.CrossRefGoogle ScholarPubMed
Munkholm, K., Brauner, J. V., Kessing, L. V., et al. Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res. 2013a;47:1119–33.CrossRefGoogle ScholarPubMed
Munkholm, K., Vinberg, M., Vedel Kessing, L. Cytokines in bipolar disorder: a systematic review and meta-analysis. J Affect Disord. 2013b;144(1–2):1627.CrossRefGoogle Scholar
Nassar, A., Azab, A. N. Effects of lithium on inflammation. ACS Chem Neurosci. 2014;5(6):451–8.CrossRefGoogle ScholarPubMed
Nery, F. G., Monkul, E. S., Hatch, J. P., et al. Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo controlled study. Hum Psychopharmacol. 2008;23(2):8794.CrossRefGoogle ScholarPubMed
Nousen, E.K., Franco, J.G., Sullivan, E.L. Unraveling the mechanisms responsible for the comorbidity between metabolic syndrome and mental health disorders. Neuroendocrinology. 2013;98(4):254–66.CrossRefGoogle ScholarPubMed
Padmos, R.C., Hillegers, M.H., Knijff, E.M., et al. A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes. Arch Gen Psychiatry. 2008;65:395407.CrossRefGoogle Scholar
Padmos, R.C., Van Baal, G.C., Vonk, R., et al. Genetic and environmental influences on pro-inflammatory monocytes in bipolar disorder: a twin study. Arch Gen Psychiatry. 2009;66:957–65.CrossRefGoogle ScholarPubMed
Pae, C.U., Lee, K.U., Han, H., et al. Tumor necrosis factor alpha gene-G308A polymorphism associated with bipolar I disorder in the Korean population. Psychiatry Res. 2004a;125:6568.CrossRefGoogle ScholarPubMed
Pae, C.U., Kim, J.J., Yu, H.S., et al. Monocyte chemoattractant protein-1 promoter −2518 polymorphism may have an influence on clinical heterogeneity of bipolar I disorder in the Korean population. Neuropsychobiology. 2004b;49:111–14.Google Scholar
Papiol, S., Rosa, A., Gutiérrez, B., et al. Interleukin-1 cluster is associated with genetic risk for schizophrenia and bipolar disorder. J Med Genet. 2004;41:219–23.CrossRefGoogle ScholarPubMed
Papiol, S., Molina, V., Desco, M., et al. Gray matter deficits in bipolar disorder are associated with genetic variability at interleukin-1 beta gene (2q13). Genes, Brain Behav. 2008;7:796801.CrossRefGoogle Scholar
Pedroso, I., Lourdusamy, A., Rietschel, M., et al. Common genetic variants and gene-expression changes associated with bipolar disorder are over-represented in brain signaling pathway genes. Biol Psychiatry. 2012;72(4):311–17.CrossRefGoogle Scholar
Perez, D.A., Vago, J.P., Athayde, R.M., et al. Switching off key signaling survival molecules to switch on the resolution of inflammation. Mediat Inflamm. 2014;829851.CrossRefGoogle ScholarPubMed
Perugi, G., Quaranta, G., Belletti, S., et al. General medical conditions in 347 bipolar disorder patients: Clinical correlates of metabolic and autoimmune-allergic diseases. J Affect Disord. 2015;170C:95103.CrossRefGoogle Scholar
Pollak, Y., Yirmiya, R. Cytokine-induced changes in mood and behaviour: implications for depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol. 2002;5(4):389–99.CrossRefGoogle ScholarPubMed
Pompili, M., Gonda, X., Serafini, G., et al. Epidemiology of suicide in bipolar disorders: a systematic review of the literature. Bipolar Disord. 2013;15:457–90.CrossRefGoogle ScholarPubMed
Porter, R. Madness: A Brief History. Oxford: Oxford University Press; 2003.Google Scholar
Rafiei, A., Hosseini, S. H., Taheri, M., et al. Influence of IL-1RN Intron 2 variable number of tandem repeats (VNTR) polymorphism on bipolar disorder. Neuropsychobiology. 2013;67:116–21.CrossRefGoogle Scholar
Raison, C.L., Capuron, L., Miller, A.H. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):2431.CrossRefGoogle Scholar
Rao, J. S., Harry, G. J., Rapoport, S. I., et al. Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Mol Psychiatry. 2010;15(4):384–92.CrossRefGoogle Scholar
Rapaport, M.H. Immune parameters in euthymic bipolar patients and normal volunteers. J Affect Disord. 1994;32:149–56.CrossRefGoogle ScholarPubMed
Roh, M. S., Lee, K. Y., Joo, E. J., et al. No association of the MCP-1 promoter A-2518G polymorphism with bipolar disorder in the Korean population. Neurosci Lett. 2007;427:15.CrossRefGoogle ScholarPubMed
Rosenblat, J. D., Cha, D. S., Mansur, R. B., et al. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog NeuroPsychopharmacol Biol Psychiatry. 2014;53:2334.CrossRefGoogle ScholarPubMed
Santtila, S., Savinainen, K., Hurme, M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol. 1998;47(3):195–8.CrossRefGoogle ScholarPubMed
Savitz, J., Preskorn, S., Teague, T.K., et al. Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, doubleblind, placebo-controlled, 232 clinical trial. BMJ Open. 2012;2(1):ID000643.CrossRefGoogle Scholar
Savitz, J. B., Price, J. L., Drevets, W. C. Neuropathological and neuromorphometric abnormalities in bipolar disorder: view from the medial prefrontal cortical network. Neurosci Biobehav Rev. 2014;42:132–47.CrossRefGoogle ScholarPubMed
Savitz, J., Dantzer, R., Wurfel, B.E., et al. Neuroprotective kynurenine metabolite indices are abnormally reduced and positively associated with hippocampal and amygdalar volume in bipolar disorder. Psychoneuroendocrinology. 2015;52:200–11.CrossRefGoogle ScholarPubMed
Schloesser, R. J., Huang, J., Klein, P. S., et al. Cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology. 2008;33(1):110–33.CrossRefGoogle ScholarPubMed
Schneider, M. R., Delbello, M. P., McNamara, R. K., et al. Neuroprogression in bipolar disorder. Bipolar Disord. 2012;14(4):356–74.CrossRefGoogle ScholarPubMed
Sharma, A.N., Bauer, I.E., Sanches, M., et al. Common biological mechanisms between bipolar disorder and type 2 diabetes: Focus on inflammation. Prog Neuropsychopharmacol Biol Psychiatry. 2014;54:289–98.CrossRefGoogle Scholar
Smith, J. A., Das, A., Ray, S. K., et al. Role of proinflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull 2012;87(1):1020.CrossRefGoogle Scholar
Smith, R.S. The macrophage theory of depression. Med Hypotheses. 1991;35(4):298306.CrossRefGoogle Scholar
Söderlund, J., Olsson, S.K., Samuelsson, M., et al. Elevation of cerebrospinal fluid interleukin-1ß in bipolar disorder. J Psychiatry Neurosci. 2011;36(2):114–18.CrossRefGoogle ScholarPubMed
Spiliotaki, M., Salpeas, V., Malitas, P., et al. Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar disorder patients. Psychoneuroendocrinology. 2006;31(6):748–60.CrossRefGoogle ScholarPubMed
Streit, W. J. Microglial senescence: does the brain’s immune system have an expiration date? Trends Neurosci. 2006;29 (90):506–10.CrossRefGoogle ScholarPubMed
Stuart, M. J., Baune, B. T. Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies. Neurosci Biobehav Rev 2014;42:93115.CrossRefGoogle ScholarPubMed
Su, S. C., Sun, M. T., Wen, M. J., et al. Brain-derived neurotrophic factor, adiponectin, and proinflammatory markers in various subtypes of depression in young men. Int J Psychiatry Med. 2011;42:211–26.CrossRefGoogle Scholar
Townsend, J. D., Torrisi, S. J., Lieberman, M. D., et al. Frontal-amygdala connectivity alterations during emotion downregulation in bipolar disorder. Biol Psychiatry. 2013;73(2):127–35.CrossRefGoogle Scholar
Watkins, C.C., Sawa, A., Pomper, M.G. (). Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application. Transl Psychiatry. 2014;21(4):e350.CrossRefGoogle Scholar
Wessely, S., Pariante, C. Fatigue, depression and chronic hepatitis C infection. Psychol Med. 2002;32(1):110.CrossRefGoogle ScholarPubMed
Wieck, A., Grassi-Oliveira, R., do Prado, C.H., et al. Differential neuroendocrine and immune responses to acute psychosocial stress in women with type 1 bipolar disorder. Brain Behav Immun. 2013;34:4755.CrossRefGoogle ScholarPubMed
Yatham, L. N., Kennedy, S. H., Parikh, S. V., et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013;15(1):144.CrossRefGoogle Scholar
Yoon, H.K., Kim, Y.K. The T allele of the interferon-gamma +874A/T polymorphism is associated with bipolar disorder. Nordic J Psychiatry. 2012;66(1):1418.CrossRefGoogle Scholar
Zetterberg, H., Jakobsson, J., Redsäter, M., et al. Blood–cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment. Psychiatry Res. 2014;217(3):143–6.CrossRefGoogle ScholarPubMed
Zunszain, P.A., Anacker, C., Cattaneo, A., et al. Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):722–9.CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats