1.Mittermaier, C, Dejaco, C, Waldhoer, T, et al. Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study. Psychosom Med. 2004; 66(1): 79–84.
2.Loftus, EV Jr. Management of extraintestinal manifestations and other complications of inflammatory bowel disease. Curr Gastroenterol Rep. 2004; 6(6): 506–513.
3.Podolsky, DK. Inflammatory bowel disease. N Engl J Med. 2002; 347(6): 417–429.
4.Scheib, P, Wirsching, M. Psychosomatic aspects of inflammatory bowel diseases. Fortschr Med. 1991; 109(12): 258–260.
5.Ramchandani, D, Schindler, B, Katz, J. Evolving concepts of psychopathology in inflammatory bowel disease: implications for treatment. Med Clin North Am. 1994; 78(6): 1321–1330.
6.Anderson, G, Maes, M. Oxidative/nitrosative stress and immuno-inflammatory pathways in depression: treatment implications. Curr Pharm Des. 2014; 20(23): 3812–3847.
7.Andrews, H, Barczak, P, Allan, RN. Psychiatric illness in patients with inflammatory bowel disease. Gut. 1987; 28(12): 1600–1604.
8.Helzer, JE, Stillings, WA, Chammas, S, Norland, CC, Alpers, DH. A controlled study of the association between ulcerative colitis and psychiatric diagnoses. Dig Dis Sci. 1982; 27(6): 513–518.
9.Helzer, JE, Chammas, S, Norland, CC, Stillings, WA, Alpers, DH. A study of the association between Crohn’s disease and psychiatric illness. Gastroenterology. 1984; 86(2): 324–330.
10.Walker, EA, Gelfand, MD, Gelfand, AN, Creed, F, Katon, WJ. The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease. Gen Hosp Psychiatry. 1996; 18(4): 220–229.
11.Walker, JR, Ediger, JP, Graff, LA, et al. The Manitoba IBD cohort study: a population-based study of the prevalence of lifetime and 12-month anxiety and mood disorders. Am J Gastroenterol. 2008; 103(8): 1989–1997.
12.Leonard, B, Maes, M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev. 2012; 36(2): 764–785.
13.Papp, M, Lakatos, PL, Hungarian IBD Study Group, et al. Haptoglobin polymorphisms are associated with Crohn’s disease, disease behavior, and extraintestinal manifestations in Hungarian patients. Dig Dis Sci. 2007; 52(5): 1279–1284.
14.Addolorato, G, Capristo, E, Stefanini, GF, Gasbarrini, G. Inflammatory bowel disease: a study of the association between anxiety and depression, physical morbidity, and nutritional status. Scand J Gastroenterol. 1997; 32(10): 1013–1021.
15.Kurina, LM, Goldacre, MJ, Yeates, D, Gill, LE. Depression and anxiety in people with inflammatory bowel disease. J Epidemiol Community Health. 2001; 55(10): 716–720.
16.Iglesias, M, Barreiro de Acosta, M, Vázquez, I, et al. Psychological impact of Crohn’s disease on patients in remission: anxiety and depression risks. Rev Esp Enferm Dig. 2009; 101(4): 249–257.
17.Hlavaty, T, Krajcovicova, A, Koller, T, et al. Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases. World J Gastroenterol. 2014; 20(42): 15787–15796.
18.Kerr, DC, Zava, DT, Piper, WT, Saturn, SR, Frei, B, Gombart, AF. Associations between vitamin D levels and depressive symptoms in healthy young adult women. Psychiatry Res. 2015; 227(1): 46–51.
19.Walker, JR, Graff, LA, Dutz, JP, Bernstein, CN. Psychiatric disorders in patients with immune-mediated inflammatory diseases: prevalence, association with disease activity, and overall patient well-being. J Rheumatol Suppl. 2011; 88: 31–35.
20.Mayer, EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011; 12(8): 453–466.
21.Collins, SM, Surette, M, Bercik, P. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol. 2012; 10(11): 735–742.
22.Bested, AC, Logan, AC, Selhub, EM. Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part I—autointoxication revisited. Gut Pathog. 2013; 5(1): 5.
23.Di Mauro, A, Neu, J, Riezzo, G, et al. Gastrointestinal function development and microbiota. Ital J Pediatr. 2013; 39: 15.
24.Shen, W, Gaskins, HR, McIntosh, MK. Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes. J Nutr Biochem. 2013; 25(3): 270–280.
25.Ghanizadeh, A, Berk, M. Molecular hydrogen: an overview of its neurobiological effects and therapeutic potential for bipolar disorder and schizophrenia. Med Gas Res. 2013; 3(1): 11.
26.Guo, S, Al-Sadi, R, Said, HM, Ma, TY. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol. 2013; 182(2): 375–387.
27.Fasano, A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012; 10(10): 1096–1100.
28.Wiest, R, Garcia-Tsao, G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005; 41(3): 422–433.
29.Anderson, G, Berk, M, Maes, M. Biological phenotypes underpin the physio-somatic symptoms of somatization, depression, and chronic fatigue syndrome. Acta Psychiatr Scand. 2014; 129(2): 83–97.
30.Maes, M, Bosmans, E, Suy, E, Vandervorst, C, De Jonckheere, C, Raus, J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology. 1990–1991; 24(3): 115–120.
31.Maes, M, Vandoolaeghe, E, Ranjan, R, Bosmans, E, Bergmans, R, Desnyder, R. Increased serum interleukin-1-receptor-antagonist concentrations in major depression. J Affect Disord. 1995; 36(1–2): 29–36.
32.Dowlati, Y, Herrmann, N, Swardfager, W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010; 67(5): 446–457.
33.Caraci, F, Spampinato, S, Sortino, MA, et al. Dysfunction of TGF-β1 signaling in Alzheimer’s disease: perspectives for neuroprotection. Cell Tissue Res. 2012; 347(1): 291–301.
34.Musil, R, Schwarz, MJ, Riedel, M, et al. Elevated macrophage migration inhibitory factor and decreased transforming growth factor-beta levels in major depression—no influence of celecoxib treatment. J Affect Disord. 2011; 134(1–3): 217–225.
35.Holtzman, S, Abbey, SE, Chan, C, Bargman, JM, Stewart, DE. A genetic predisposition to produce low levels of IL-10 is related to depressive symptoms: a pilot study of patients with end stage renal disease. Psychosomatics. 2012; 53(2): 155–161.
36.Roque, S, Correia-Neves, M, Mesquita, AR, Palha, JA, Sousa, N. Interleukin-10: a key cytokine in depression? Cardiovasc Psychiatry Neurol. 2009; 2009: 187894.
37.Maes, M, Anderson, G, Kubera, M, Berk, M. Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? Expert Opin Ther Targets. 2014; 18(5): 495–512.
38.Maes, M, Leonard, BE, Myint, AM, Kubera, M, Verkerk, R. The new “5-HT” hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35(3): 702–721.
39.Maes, M. Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35(3): 664–675.
40.Beurel, E, Harrington, LE, Jope, RS. Inflammatory T helper 17 cells promote depression-like behavior in mice. Biol Psychiatry. 2013; 73(7): 622–630.
41.Wong, CK, Cao, J, Yin, YB, Lam, CWK. Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism. Eur Respir J. 2010; 35(4): 883–893.
42.Maes, M, Scharpe, S, Bosmans, E, et al. Disturbances in acute phase plasma proteins during melancholia: additional evidence for the presence of an inflammatory process during that illness. Prog Neuropsychopharmacol Biol Psychiatry. 1992; 16(4): 501–515.
43.Sluzewska, A, Rybakowski, J, Bosmans, E, et al. Indicators of immune activation in major depression. Psychiatry Res. 1996; 64(3): 161–167.
44.Fãnanás, L, Moral, P, Gutiérrez, B, et al. Haptoglobin phenotypes and gene frequencies in bipolar disorder: an association study in family-history subgroups. Hum Hered. 1997; 47(1): 27–32.
45.Maes, M, Vandoolaeghe, E, Neels, H, et al. Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness. Biol Psychiatry. 1997; 42(5): 349–358.
46.Nowak, G, Szewczyk, B, Pilc, A. Zinc and depression: an update. Pharmacol Rep. 2005; 57(6): 713–718.
47.Song, C, Dinan, T, Leonard, BE. Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord. 1994; 30(4): 283–288.
48.Berk, M, Wadee, AA, Kuschke, RH, O’Neill-Kerr, A. Acute phase proteins in major depression. J Psychosom Res. 1997; 43(5): 529–534.
49.Maes, M, Galecki, P, Chang, YS, Berk, M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35(3): 676–692.
50.Michel, TM, Frangou, S, Camara, S, et al. Altered glial cell line-derived neurotrophic factor (GDNF) concentrations in the brain of patients with depressive disorder: a comparative post-mortem study. Eur Psychiatry. 2008; 23(6): 413–420.
51.Massudi, H, Grant, R, Braidy, N, Guest, J, Farnsworth, B, Guillemin, GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012; 7(7): e42357.
52.Rybka, J, Kędziora-Kornatowska, K, Banaś-Leżańska, P, et al. Interplay between the pro-oxidant and antioxidant systems and proinflammatory cytokine levels, in relation to iron metabolism and the erythron in depression. Free Radic Biol Med. 2013; 63: 187–194.
53.Phillips, AC, Robertson, T, Carroll, D, et al. Do symptoms of depression predict telomere length? Evidence from the west of Scotland twenty-07 study. Psychosom Med. 2013; 75(3): 288–296.
54.Wolkowitz, OM, Mellon, SH, Epel, ES, et al. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress—preliminary findings. PLoS One. 2011; 6(3): e17837.
55.Maes, M, Kubera, M, Mihaylova, I, et al. Increased autoimmune responses against auto-epitopes modified by oxidative and nitrosative damage in depression: implications for the pathways to chronic depression and neuroprogression. J Affect Disord. 2013; 149(1–3): 23–29.
56.Jacka, FN, Pasco, JA, Mykletun, A, et al. Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry. 2010; 167(3): 305–311.
57.Deberdt, R, Van Hooren, J, Biesbrouck, M, Amery, W. Antinuclear factor-positive mental depression: a single disease entity? Biol Psychiatry. 1976; 11(1): 69–74.
58.Maes, M, Meltzer, H, Jacobs, J, et al. Autoimmunity in depression: increased antiphospholipid autoantibodies. Acta Psychiatr Scand. 1993; 87(3): 160–166.
59.Maes, M, Bosmans, E, Suy, E, Vandervorst, C, DeJonckheere, C, Raus, J. Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 beta and soluble interleukin-2 receptor production. Acta Psychiatr Scand. 1991; 84(4): 379–386.
60.Lapteva, L, Nowak, M, Yarboro, CH, et al. Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum. 2006; 54(8): 2505–2514.
61.Karimifar, M, Sharifi, I, Shafiey, K. Anti-ribosomal P antibodies related to depression in early clinical course of systemic lupus erythematosus. J Res Med Sci. 2013; 18(10): 860–864.
62.Maes, M, Mihaylova, I, Kubera, M, Leunis, J-C, Geffard, M. IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology. J Affect Disord. 2011; 135(1–3): 414–418.
63.Maes, M, Kubera, M, Leunis, JC, Berk, M, Geffard, M, Bosmans, E. In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatr Scand. 2013; 127(5): 344–354.
64.Lapin, IP. Neurokynurenines (NEKY) as common neurochemical links of stress and anxiety. Adv Exp Med Biol. 2003; 527: 121–125.
65.O’Connor, JC, Lawson, MA, André, C, et al. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry. 2009; 14(5): 511–522.
66.Oxenkrug, GF. Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging. Ann N Y Acad Sci. 2007; 1122: 35–49.
67.Maes, M, Bonaccorso, S, Marino, V, et al. Treatment with interferon-alpha (IFN alpha) of hepatitis C patients induces lower serum dipeptidyl peptidase IV activity, which is related to IFN alpha-induced depressive and anxiety symptoms and immune activation. Mol Psychiatry. 2001; 6(4): 475–480.
68.Bonaccorso, S, Puzella, A, Marino, V, et al. Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. Psychiatry Res. 2001; 105(1–2): 45–55.
69.Bonaccorso, S, Marino, V, Biondi, M, Grimaldi, F, Ippoliti, F, Maes, M. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord. 2002; 72(3): 237–241.
70.Maes, M, Kubera, M, Leunis, J-C. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008; 29(1): 117–124.
71.Yirmiya, R. Endotoxin produces a depressive-like episode in rats. Brain Res. 1996; 711(1–2): 163–174.
72.De La Garza, R II. Endotoxin- or pro-inflammatory cytokine-induced sickness behavior as an animal model of depression: focus on anhedonia. Neurosci Biobehav Rev. 2005; 29(4–5): 761–770.
73.Lucas, K, Maes, M. Role of the Toll like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013; 48(1): 190–204.
74.Mozaffari, S, Abdollahi, M. Melatonin, a promising supplement in inflammatory bowel disease: a comprehensive review of evidences. Curr Pharm Des. 2011; 17(38): 4372–4378.
75.Sun, X, Shao, Y, Jin, Y, et al. Melatonin reduces bacterial translocation by preventing damage to the intestinal mucosa in an experimental severe acute pancreatitis rat model. Exp Ther Med. 2013; 6(6): 1343–1349.
76.Chojnacki, C, Walecka-Kapica, E, Mokwinska, M, et al. Influence of tianeptine on melatonin homeostasis and psychosomatic symptoms in patients with irritable bowel syndrome. J Physiol Pharmacol. 2013; 64(2): 177–183.
77.Maloy, KJ, Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011; 474(7351): 298–306.
78.Sarra, M, Pallone, F, Macdonald, TT, Monteleone, G. IL-23/IL-17 axis in IBD. Inflamm Bowel Dis. 2010; 16(10): 1808–1813.
79.Sekut, L, Connolly, K. AntiTNF-alpha agents in the treatment of inflammation. Expert Opin Investig Drugs. 1998; 7(11): 1825–1839.
80.Yan, SLS, Russell, J, Granger, DN. Platelet activation and platelet-leukocyte aggregation elicited in experimental colitis are mediated by interleukin-6. Inflamm Bowel Dis. 2014; 20(2): 353–362.
81.Zhang, SJ, Wang, L, Ming, L, et al. Blockade of IL-6 signal exacerbates acute inflammatory bowel disease via inhibiting IL-17 producing in activated CD4+ Th17 population. Eur Rev Med Pharmacol Sci. 2013; 17(24): 3291–3295.
82.McGeachy, MJ, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007; 8(12): 1390–1397.
83.Kuboyama, S. Increased circulating levels of interleukin-1 receptor antagonist in patients with inflammatory bowel disease. Kurume Med J. 1998; 45(1): 33–37.
84.Cominelli, F, Pizarro, TT. Interleukin-1 and interleukin-1 receptor antagonist in inflammatory bowel disease. Aliment Pharmacol Ther. 1996; 10(Suppl 2): 49–53; discussion 54.
85.Kaser, A, Zeissig, S, Blumberg, RS. Inflammatory bowel disease. Annu Rev Immunol. 2010; 28: 573–621.
86.Jovani, M, Fiorino, G, Danese, S. Anti-IL-13 in inflammatory bowel disease: from the bench to the bedside. Curr Drug Targets. 2013; 14(12): 1444–1452.
87.Wolk, K, Warszawska, K, Hoeflich, C, et al. Deficiency of IL-22 contributes to a chronic inflammatory disease: pathogenetic mechanisms in acne inversa. J Immunol. 2011; 186(2): 1228–1239.
88.Eken, A, Singh, AK, Treuting, PM, Oukka, M. IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism. Mucosal Immunol. 2014; 7(1): 143–154.
89.Maloy, KJ, Kullberg, MC. IL-23 and Th17 cytokines in intestinal homeostasis. Mucosal Immunol. 2008; 1(5): 339–349.
90.Song, L, Zhou, R, Huang, S, et al. High intestinal and systemic levels of interleukin-23/T-helper 17 pathway in Chinese patients with inflammatory bowel disease. Mediators Inflamm. 2013; 2013: 425915.
91.Troncone, E, Marafini, I, Pallone, F, Monteleone, G. Th17 cytokines in inflammatory bowel diseases: discerning the good from the bad. Int Rev Immunol. 2013; 32(5–6): 526–533.
92.Rossi, M, Bot, A. The Th17 cell population and the immune homeostasis of the gastrointestinal tract. Int Rev Immunol. 2013; 32(5–6): 471–474.
93.Tao, F, Qian, C, Guo, W, Luo, Q, Xu, Q, Sun, Y. Inhibition of Th1/Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin. Biochem Pharmacol. 2013; 85(6): 798–807.
94.He, Y, Lin, L-J, Zheng, C-Q, Jin, Y, Lin, Y. Cytokine expression and the role of Thl7 cells in mice colitis. Hepatogastroenterology. 2012; 59(118): 1809–1813.
95.Pak, S, Holland, N, Garnett, EA, et al. Cytokine profiles in peripheral blood of children and adults with Crohn disease. J Pediatr Gastroenterol Nutr. 2012; 54(6): 769–775.
96.Beltrán, CJ, Candia, E, Erranz, B, et al. Peripheral cytokine profile in Chilean patients with Crohn’s disease and ulcerative colitis. Eur Cytokine Netw. 2009; 20(1): 33–38.
97.Ciećko-Michalska, I, Fedak, D, Mach, T. Neopterin in assessing the activity of inflammatory bowel diseases: ulcerative colitis and Crohn’s disease. Przegl Lek. 2010; 67: 1262–1265.
98.Husain, N, Tokoro, K, Popov, JM, Naides, SJ, Kwasny, MJ, Buchman, AL. Neopterin concentration as an index of disease activity in Crohn’s disease and ulcerative colitis. J Clin Gastroenterol. 2013; 47(3): 246–251.
99.Matsuura, T, West, GA, Klein, JS, Ferraris, L, Fiocchi, C. Soluble interleukin 2 and CD8 and CD4 receptors in inflammatory bowel disease. Gastroenterology. 1992; 102(6): 2006–2014.
100.Van Kemseke, C, Belaiche, J, Louis, E. Frequently relapsing Crohn’s disease is characterized by persistent elevation in interleukin-6 and soluble interleukin-2 receptor serum levels during remission. Int J Colorectal Dis. 2000; 15(4): 206–210.
101.Dalekos, GN, Manoussakis, MN, Goussia, AC, Tsianos, EV, Moutsopoulos, HM. Soluble interleukin-2 receptors, antineutrophil cytoplasmic antibodies, and other autoantibodies in patients with ulcerative colitis. Gut. 1993; 34(5): 658–664.
102.Nielsen, OH, Brynskov, J. Soluble interleukin-2 receptors in ulcerative colitis. Mediators Inflamm. 1993; 2(2): 115–118.
103.Srivastava, MD, Rossi, TM, Lebenthal, E. Serum soluble interleukin-2 receptor, soluble CD8 and soluble intercellular adhesion molecule-1 levels in Crohn’s disease, celiac disease, and systemic lupus erythematosus. Res Commun Mol Pathol Pharmacol. 1995; 87(1): 21–26.
104.Kiss, LS, Szamosi, T, Molnar, T, et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease. Aliment Pharmacol Ther. 2011; 34(8): 911–922.
105.Kiss, LS, Papp, M, Lovasz, BD, et al. High-sensitivity C-reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn’s disease: a marker for patient classification? Inflamm Bowel Dis. 2012; 18(9): 1647–1654.
106.Weeke, B, Jarnum, S. Serum concentration of 19 serum proteins in Crohn’s disease and ulcerative colitis. Gut. 1971; 12(4): 297–302.
107.Alkhouri, RH, Hashmi, H, Baker, RD, Gelfond, D, Baker, SS. Vitamin and mineral status in patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2013; 56(1): 89–92.
108.Hwang, C, Ross, V, Mahadevan, U. Micronutrient deficiencies in inflammatory bowel disease: from A to zinc. Inflamm Bowel Dis. 2012; 18(10): 1961–1981.
109.Biancheri, P, Giuffrida, P, Docena, GH, MacDonald, TT, Corazza, GR, Di Sabatino, A. The role of transforming growth factor (TGF)-β in modulating the immune response and fibrogenesis in the gut. Cytokine Growth Factor Rev. 2014; 25(1): 45–55.
110.Lv, H, Jiang, Y, Li, J, et al. Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease. Mol Biol Rep. 2014; 41(3): 1299–1310.
111.Li, M, Wang, B, Zhang, M, et al. Symbiotic gut microbes modulate human metabolic phenotypes. Proc Natl Acad Sci U S A. 2008; 105(6): 2117–2122.
112.Izcue, A, Coombes, JL, Powrie, F. Regulatory lymphocytes and intestinal inflammation. Annu. Rev. Immunol. 2009; 27: 313–338.
113.Martin, FP, Rezzi, S, Philippe, D, et al. Metabolic assessment of gradual development of moderate experimental colitis in IL-10 deficient mice. J Proteome Res. 2009; 8(5): 2376–2387.
114.Glocker, EO, Kotlarz, D, Boztug, K, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009; 361(21): 2033–2045.
115.Zhu, H, Li, YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood). 2012; 237(5): 474–480.
116.Hatsugai, M, Kurokawa, MS, Kouro, T, et al. Protein profiles of peripheral blood mononuclear cells are useful for differential diagnosis of ulcerative colitis and Crohn’s disease. J Gastroenterol. 2010; 45(5): 488–500.
117.Rachmilewitz, D, Stamler, JS, Karmeli, F, et al. Peroxynitrite-induced rat colitis—a new model of colonic inflammation. Gastroenterology. 1993; 105(6): 1681–1688.
118.Naito, Y, Takagi, T, Yoshikawa, T. Molecular fingerprints of neutrophil-dependent oxidative stress in inflammatory bowel disease. J Gastroenterol. 2007; 42(10): 787–798.
119.Kolesov, SA, Korkotashvili, LV, Yazykova, AB, Fedulova, EN, Tutina, OA, Tolkacheva, NI. S-nitrosothiols, nitric oxide and proinflammatory cytokines in children with inflammatory bowel disease. Clin Lab. 2013; 59(9–10): 953–957.
120.Achitei, D, Ciobica, A, Balan, G, Gologan, E, Stanciu, C, Stefanescu, G. Different profile of peripheral antioxidant enzymes and lipid peroxidation in active and non-active inflammatory bowel disease patients. Dig Dis Sci. 2013; 58(5): 1244–1249.
121.Alzoghaibi, MA. Concepts of oxidative stress and antioxidant defense in Crohn’s disease. World J Gastroenterol. 2013; 19(39): 6540–6547.
122.Nanau, RM, Neuman, MG. Metabolome and inflammasome in inflammatory bowel disease. Transl Res. 2012; 160(1): 1–28.
123.Martinović, Z, Perisić, K, Pejnović, N, Lukacević, S, Rabrenović, L, Petrović, M. Antiphospholipid antibodies in inflammatory bowel diseases. Vojnosanit Pregl. 1998; 55(2 Suppl): 47–49.
124.O’Donnell, S, O’Sullivan, M, O’Morain, CA, Ryan, BM. The clinical significance of antimicrobial serologic responses within an Irish Crohn’s disease population. Eur J Gastroenterol Hepatol. 2013; 25(12): 1464–1469.
125.Dotan, I. New serologic markers for inflammatory bowel disease diagnosis. Dig Dis. 2010; 28(3): 418–423.
126.Forrest, CM, Gould, SR, Darlington, LG, Stone, TW. Levels of purine, kynurenine and lipid peroxidation products in patients with inflammatory bowel disease. Adv Exp Med Biol. 2003; 527: 395–400.
127.Gupta, NK, Thaker, AI, Kanuri, N, et al. Serum analysis of tryptophan catabolism pathway: correlation with Crohn’s disease activity. Inflamm Bowel Dis. 2012; 18(7): 1214–1220.
128.Lin, HM, Barnett, MP, Roy, NC, et al. Metabolomic analysis identifies inflammatory and noninflammatory metabolic effects of genetic modification in a mouse model of Crohn’s disease. J Proteome Res. 2010; 9: 1965–1975.
129.Wolf, AM, Wolf, D, Rumpold, H, et al. Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease. Clin Immunol. 2004; 113(1): 47–55.
130.Ciorba, MA. Indoleamine 2,3 dioxygenase in intestinal disease. Curr Opin Gastroenterol. 2013; 29(2): 146–152.
131.Xavier, RJ, Podolsky, DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007; 448(7152): 427–434.
132.Gassler, N, Rohr, C, Schneider, A, et al. Inflammatory bowel disease is associated with changes of enterocytic junctions. Am J Physiol Gastrointest Liver Physiol. 2001; 281(1): G216–G228.
133.Qin, X. Etiology of inflammatory bowel disease: a unified hypothesis. World J Gastroenterol. 2012; 18(15): 1708–1722.
134.Söderholm, JD, Peterson, KH, Olaison, G, et al. Epithelial permeability to proteins in the noninflamed ileum of Crohn’s disease? Gastroenterology. 1999; 117(1): 65–72.
135.Katz, KD, Hollander, D, Vadheim, CM, et al. Intestinal permeability in patients with Crohn’s disease and their healthy relatives. Gastroenterology. 1989; 97(4): 927–931.
136.Lepage, P, Häsler, R, Spehlmann, ME, et al. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology. 2011; 141(1): 227–236.
137.Machiels, K, Joossens, M, Sabino, J, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014; 63(8): 1275–1283.
138.Montrose, DC, Scherl, EJ, Bosworth, BP, et al. S1P1 localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity. J Lipid Res. 2013; 54(3): 843–851.
139.Greenspon, J, Li, R, Xiao, L, et al. Sphingosine-1-phosphate regulates the expression of adherens junction protein E-cadherin and enhances intestinal epithelial cell barrier function. Dig Dis Sci. 2011; 56(5): 1342–1353.
140.Chen, Y, Jiang, T, Chen, P, et al. Emerging tendency towards autoimmune process in major depressive patients: a novel insight from Th17 cells. Psychiatry Res. 2011; 188(2): 224–230.
141.Sluzewska, A, Sobieska, M, Rybakowski, JK. Changes in acute-phase proteins during lithium potentiation of antidepressants in refractory depression. Neuropsychobiology. 1997; 35(5): 123–127.
142.Pasco, JA, Nicholson, GC, Williams, LJ, et al. Association of high-sensitivity C-reactive protein with de novo major depression. Br J Psychiatry. 2010; 197(5): 372–377.
143.Hsuchou, H, Kastin, AJ, Mishra, PK, Pan, W. C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation. Cell Physiol Biochem. 2012; 30(5): 1109–1119.
144.Hannestad, J, Gallezot, JD, Schafbauer, T, et al. Endotoxin-induced systemic inflammation activates microglia: [11C]PBR28 positron emission tomography in nonhuman primates. Neuroimage. 2012; 63(1): 232–239.
145.Bian, Y, Zhao, X, Li, M, Zeng, S, Zhao, B. Various roles of astrocytes during recovery from repeated exposure to different doses of lipopolysaccharide. Behav Brain Res. 2013; 253: 253–261.
146.Seo, JS, Park, JY, Choi, J, et al. NADPH oxidase mediates depressive behavior induced by chronic stress in mice. J Neurosci. 2012; 32(28): 9690–9699.
147.Maes, M, Fišar, Z, Medina, M, Scapagnini, G, Nowak, G, Berk, M. New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology. 2012; 20(3): 127–150.
148.Gerasimidis, K, Edwards, C, Stefanowicz, F, et al. Micronutrient status in children with IBD: true deficiencies or epiphenomenon of the systemic inflammatory response. J Pediatr Gastroenterol Nutr. 2013; 56(6): e50–e51.
149.Grønli, O, Kvamme, JM, Friborg, O, Wynn, R. Zinc deficiency is common in several psychiatric disorders. PLoS One. 2013; 8(12): e82793.
150.Aggett, PJ, Harries, JT. Current status of zinc in health and disease states. Arch Dis Child. 1979; 54(12): 909–917.
151.Rath, E, Haller, D. Mitochondria at the interface between danger signaling and metabolism: role of unfolded protein responses in chronic inflammation. Inflamm Bowel Dis. 2012; 18(7): 1364–1377.
152.Shao, L, Martin, MV, Watson, SJ, et al. Mitochondrial involvement in psychiatric disorders. Ann Med. 2008; 40(4): 281–295.
153.Tan, DX, Manchester, LC, Liu, X, Rosales-Corral, SA, Acuna-Castroviejo, D, Reiter, RJ. Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin’s primary function and evolution in eukaryotes. J Pineal Res. 2013; 54(2): 127–138.
154.Post, RM, Rubinow, DR, Ballenger, JC. Conditioning and sensitisation in the longitudinal course of affective illness. Br J Psychiatry. 1986; 149(2): 191–201.
155.Rhee, I, Zhong, M-C, Reizis, B, Cheong, C, Veillette, A. Control of dendritic cell migration, T cell-dependent immunity and autoimmunity by protein tyrosine phosphatase PTPN12 expressed in dendritic cells. Mol Cell Biol. 2014; 34(5): 888–899.
156.Kubera, M, Curzytek, K, Duda, W, et al. A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months. Brain Behav Immun. 2013; 31: 96–104.
157.Lawson, MA, Parrott, JM, McCusker, RH, Dantzer, R, Kelley, KW, O’Connor, JC. Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors. Journal of Neuroinflammation. 2013; 10(1): 87.
158.Doenlen, R, Krügel, U, Wirth, T, et al. Electrical activity in rat cortico-limbic structures after single or repeated administration of lipopolysaccharide or staphylococcal enterotoxin B. Proc Biol Sci. 2011; 278(1713): 1864–1872.
159.Haba, R, Shintani, N, Onaka, Y, et al. Lipopolysaccharide affects exploratory behaviors toward novel objects by impairing cognition and/or motivation in mice: possible role of activation of the central amygdala. Behav Brain Res. 2012; 228(2): 423–431.
160.Dobos, N, de Vries, EF, Kema, IP, et al. The role of indoleamine 2,3-dioxygenase in a mouse model of neuroinflammation-induced depression. J Alzheimers Dis. 2012; 28(4): 905–915.
161.Salazar, A, Gonzalez-Rivera, BL, Redus, L, Parrott, JM, O’Connor, JC. Indoleamine 2,3-dioxygenase mediates anhedonia and anxiety-like behaviors caused by peripheral lipopolysaccharide immune challenge. Horm Behav. 2012; 62(3): 202–209.
162.Levin, AD, van den Brink, GR. Selective inhibition of mucosal serotonin as treatment for IBD? Gut. 2014; 63(6): 866–867.
163.Collins, S, Verdu, E, Denou, E, Bercik, P. The role of pathogenic microbes and commensal bacteria in irritable bowel syndrome. Dig Dis. 2009; 27(Suppl 1): 85–89.
164.Bailey, MT, Dowd, SE, Parry, NM, Galley, JD, Schauer, DB, Lyte, M. Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by Citrobacter rodentium. Infect Immun. 2010; 78(4): 1509–1519.
165.Ghia, JE, Blennerhassett, P, Deng, Y, Verdu, EF, Khan, WI, Collins, SM. Reactivation of inflammatory bowel disease in a mouse model of depression. Gastroenterology. 2009; 136(7): 2280–2288.
166.Bonaz, BL, Bernstein, CN. Brain-gut interactions in inflammatory bowel disease. Gastroenterology. 2013; 144(1): 36–49.
167.D'Haens, GR, Panaccione, R, Higgins, PD, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol. 2011; 106(2): 199–212; quiz 213.
168.Banovic, I, Gilibert, D, Cosnes, J. Perception of improved state of health and subjective quality of life in Crohn’s disease patients treated with infliximab. J Crohns Colitis. 2009; 3(1): 25–31.
169.Raison, CL, Rutherford, RE, Woolwine, BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013; 70(1): 31–41.
170.Tyring, S, Gottlieb, A, Papp, K, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet. 2006; 367(9504): 29–35.
171.Krügel, U, Fischer, J, Radicke, S, Sack, U, Himmerich, H. Antidepressant effects of TNF-α blockade in an animal model of depression. J Psychiatr Res. 2013; 47(5): 611–616.
172.Sun, Z, Lasson, A, Olanders, K, Deng, X, Andersson, R. Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion—effects of pretreatment with N-acetyl-L-cysteine and indomethacin. Dig Liver Dis. 2002; 34(8): 560–569.
173.Berk, M, Copolov, DL, Dean, O, et al. N-acetyl cysteine for depressive symptoms in bipolar disorder—a double-blind randomized placebo-controlled trial. Biol Psychiatry. 2008; 64(6): 468–475.
174.Maes, M, Twisk, FN, Kubera, M, Ringel, K, Leunis, JC, Geffard, M. Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome. J Affect Disord. 2012; 136(3): 909–917.
175.Goodhand, JR, Greig, FI, Koodun, Y, et al. Do antidepressants influence the disease course in inflammatory bowel disease? A retrospective case-matched observational study. Inflamm Bowel Dis. 2012; 18(7): 1232–1239.
176.Mikocka-Walus, AA, Gordon, AL, Stewart, BJ, Andrews, JM. A magic pill? A qualitative analysis of patients’ views on the role of antidepressant therapy in inflammatory bowel disease (IBD). BMC Gastroenterol. 2012; 12: 93.
177.Mikocka-Walus, A, Andrews, JM. Attitudes towards antidepressants among people living with inflammatory bowel disease: an online Australia-wide survey. J Crohns Colitis. 2014; 8(4): 296–303.
178.Iskandar, HN, Cassell, B, Kanuri, N, et al. Tricyclic antidepressants for management of residual symptoms in inflammatory bowel disease. J Clin Gastroenterol. 2014; 48(5): 423–429.
179.Szigethy, E, Bujoreanu, SI, Youk, AO, et al. Randomized efficacy trial of two psychotherapies for depression in youth with inflammatory bowel disease. J Am Acad Child Adolesc Psychiatry. 2014; 53(7): 726–735.