Advertisement

Molecular Neurobiology

, Volume 53, Issue 5, pp 2927–2935 | Cite as

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

  • Michael Maes
  • Gabriel Nowak
  • Javier R. Caso
  • Juan Carlos Leza
  • Cai Song
  • Marta Kubera
  • Hans Klein
  • Piotr Galecki
  • Cristiano Noto
  • Enrico Glaab
  • Rudi Balling
  • Michael Berk
Article

Abstract

Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.

Keywords

Depression Immune Inflammation Neuroprogression Oxidative and nitrosative stress Leaky gut IDO TRYCATs 

Notes

Acknowledgments

MB is supported by a NHMRC Senior Principal Research Fellowship (GNT1059660).

Conflict of Interest

MB has received Grant/Research Support from the National Institute of Health (USA), Simons Foundation, CRC for Mental Health, Stanley Medical Research Institute, Medical Benefits Fund, National Health and Medical Research Council (NHMRC of Australia), Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma, Servier, and Astra Zeneca. He has been a paid consultant for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, and Pfizer and a paid speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, Sanofi Synthelabo, Solvay, and Wyeth.

Other authors do not report any conflict of interest.

Contributions

All authors contributed equally to the paper.

Funding

There was no specific funding for this specific study.

We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

References

  1. 1.
    Kirsch I (2009) Antidepressants and the placebo response. Epidemiol Psychiatr Soc 18(4):318–322CrossRefGoogle Scholar
  2. 2.
    Maes M (1993) A review on the acute phase response in major depression. Rev Neurosci 4(4):407–416CrossRefPubMedGoogle Scholar
  3. 3.
    Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, Allen NB, Stuart AL, Hayley AC, Byrne ML, Maes M (2013) So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 11:200CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Fond G, Hamdani N, Kapczinski F, Boukouaci W, Drancourt N, Dargel A, Oliveira J, Le Guen E, Marlinge E, Tamouza R, Leboyer M (2014) Effectiveness and tolerance of anti-inflammatory drugs’ add-on therapy in major mental disorders: a systematic qualitative review. Acta Psychiatr Scand 129(3):163–179CrossRefPubMedGoogle Scholar
  5. 5.
    Köhler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, Krogh J (2014) Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2014.1611 PubMedGoogle Scholar
  6. 6.
    Maes M, Bosmans E, Suy E, Vandervorst C, DeJonckheere C, Raus J (1991) Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 beta and soluble interleukin-2 receptor production. Acta Psychiatr Scand 84(4):379–386CrossRefPubMedGoogle Scholar
  7. 7.
    Song C, Dinan T, Leonard BE (1994) Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord 30(4):283–288CrossRefPubMedGoogle Scholar
  8. 8.
    Maes M, Fišar Z, Medina M, Scapagnini G, Nowak G, Berk M (2012) 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 20(3):127–150CrossRefPubMedGoogle Scholar
  9. 9.
    Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J (1990) Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology 24(3):115–120CrossRefPubMedGoogle Scholar
  10. 10.
    Peet M, Murphy B, Shay J, Horrobin D (1998) Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry 43(5):315–319CrossRefPubMedGoogle Scholar
  11. 11.
    Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY (1999) Lowered omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 85(3):275–291CrossRefPubMedGoogle Scholar
  12. 12.
    Maes M, Galecki P, Chang YS, Berk M (2011) 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 35(3):676–692CrossRefPubMedGoogle Scholar
  13. 13.
    Maes M, De Vos N, Pioli R, Demedts P, Wauters A, Neels H, Christophe A (2000) Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness. J Affect Disord 58(3):241–246CrossRefPubMedGoogle Scholar
  14. 14.
    Maes M, Mihaylova I, Kubera M, Leunis JC, Geffard M (2011) IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology. J Affect Disord 135:414–418CrossRefPubMedGoogle Scholar
  15. 15.
    Maes M, Kubera M, Leunis JC (2008) 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. Neuroendocrinol Lett 29(1):117–124PubMedGoogle Scholar
  16. 16.
    Lucas K, Maes M (2013) Role of the toll like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol 48(1):190–204CrossRefPubMedGoogle Scholar
  17. 17.
    Liu J, Buisman-Pijlman F, Hutchinson MR (2014) Toll-like receptor 4: innate immune regulator of neuroimmune and neuroendocrine interactions in stress and major depressive disorder. Front Neurosci 8:309PubMedPubMedCentralGoogle Scholar
  18. 18.
    Hung YY, Kang HY, Huang KW, Huang TL (2014) Association between toll-like receptors expression and major depressive disorder. Psychiatry Res. doi: 10.1016/j.psychres.2014.07.074 Google Scholar
  19. 19.
    Kéri S, Szabó C, Kelemen O (2014) Expression of toll-like receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder. Brain Behav Immun 40:235–243CrossRefPubMedGoogle Scholar
  20. 20.
    Maes M, Meltzer HY, Scharpé S, Bosmans E, Suy E, De Meester I, Calabrese J, Cosyns P (1993) Relationships between lower plasma L-tryptophan levels and immune-inflammatory variables in depression. Psychiatry Res 49(2):151–165CrossRefPubMedGoogle Scholar
  21. 21.
    Bonaccorso S, Meltzer H, Maes M (2000) Psychological and behavioural effects of interferons. Curr Opin Psychiatry 13:673–677CrossRefGoogle Scholar
  22. 22.
    Song C, Lin A, Bonaccorso S, Heide C, Verkerk R, Kenis G, Bosmans E, Scharpe S, Whelan A, Cosyns P, de Jongh R, Maes M (1998) The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 49(3):211–219CrossRefPubMedGoogle Scholar
  23. 23.
    Maes M, Smith R, Christophe A, Vandoolaeghe E, Van Gastel A, Neels H, Demedts P, Wauters A, Meltzer HY (1997) Lower serum high-density lipoprotein cholesterol (HDL-C) in major depression and in depressed men with serious suicidal attempts: relationship with immune-inflammatory markers. Acta Psychiatr Scand 95(3):212–221CrossRefPubMedGoogle Scholar
  24. 24.
    Kubera M, Symbirtsev A, Basta-Kaim A, Borycz J, Roman A, Papp M, Claesson M (1996) Effect of chronic treatment with imipramine on interleukin 1 and interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression. Pol J Pharmacol 48(5):503–506PubMedGoogle Scholar
  25. 25.
    Kubera M, Obuchowicz E, Goehler L, Brzeszcz J, Maes M (2011) In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 35(3):744–759CrossRefPubMedGoogle Scholar
  26. 26.
    Kubera M, Curzytek K, Duda W, Leskiewicz M, Basta-Kaim A, Budziszewska B, Roman A, Zajicova A, Holan V, Szczesny E, Lason W, Maes M (2013) A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months. Brain Behav Immun 31:96–104CrossRefPubMedGoogle Scholar
  27. 27.
    Gárate I, García-Bueno B, Madrigal JL, Bravo L, Berrocoso E, Caso JR, Micó JA, Leza JC (2011) Origin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression. J Neuroinflammation 8:151CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gárate I, Garcia-Bueno B, Madrigal JL, Caso JR, Alou L, Gomez-Lus ML, Micó JA, Leza JC (2013) Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway. Biol Psychiatry 73(1):32–43CrossRefPubMedGoogle Scholar
  29. 29.
    Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M (2009) The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 24(1):27–53CrossRefPubMedGoogle Scholar
  30. 30.
    Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, Magalhães PV, Amminger P, McGorry P, Malhi GS (2011) Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 35(3):804–817CrossRefPubMedGoogle Scholar
  31. 31.
    Moylan S, Maes M, Wray NR, Berk M (2013) The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry 18(5):595–606CrossRefPubMedGoogle Scholar
  32. 32.
    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):245–255CrossRefPubMedGoogle Scholar
  33. 33.
    Maes M, Smith R, Scharpe S (1995) The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology 20(2):111–116CrossRefPubMedGoogle Scholar
  34. 34.
    Maes M, Kubera M, Obuchowiczwa E, Goehler L, Brzeszcz J (2011) Depression’s multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways. Neuroendocrinol Lett 32(1):7–24PubMedGoogle Scholar
  35. 35.
    Musselman DL, Miller AH, Porter MR, Manatunga A, Gao F, Penna S, Pearce BD, Landry J, Glover S, McDaniel JS, Nemeroff CB (2011) Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry 158(8):1252–1257CrossRefGoogle Scholar
  36. 36.
    Lampert R, Bremner JD, Su S, Miller A, Lee F, Cheema F, Goldberg J, Vaccarino V (2008) Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men. Am Heart J 156(4):759.e1–759.e7CrossRefGoogle Scholar
  37. 37.
    Vanuytsel T, Vermeire S, Cleynen I (2013) The role of Haptoglobin and its related protein, zonulin, in inflammatory bowel disease. Tissue Barriers 1(5), e27321CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Alayash AI (2011) Haptoglobin: old protein with new functions. Clin Chim Acta 412(7–8):493–498CrossRefPubMedGoogle Scholar
  39. 39.
    Quaye IK (2008) Haptoglobin, inflammation and disease. Trans R Soc Trop Med Hyg 102(8):735–742CrossRefPubMedGoogle Scholar
  40. 40.
    Rose-John S (2012) IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 8:1237–1247CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R (1995) Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 34(4):301–309CrossRefPubMedGoogle Scholar
  42. 42.
    Maes M, Anderson G, Kubera M, Berk M (2014) Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? Expert Opin Ther Targets 18(5):495–512CrossRefPubMedGoogle Scholar
  43. 43.
    Loscalzo J, Kohane I, Barabasi AL (2007) Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol Syst Biol 3:124CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    López-Muñoz F, Alamo C (2009) Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des 15:1563–1586CrossRefPubMedGoogle Scholar
  45. 45.
    Moncrieff J, Wessely S, Hardy R (2004) Active placebos versus antidepressants for depression. Cochrane Database Syst Rev 2004, CD003012Google Scholar
  46. 46.
    Turner EH, Loftis JM, Blackwell AD (2006) Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther 109(3):325–338CrossRefPubMedGoogle Scholar
  47. 47.
    Słuzewska A, Rybakowski JK, Laciak M, Mackiewicz A, Sobieska M, Wiktorowicz K (1995) Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Ann N Y Acad Sci 762:474–476CrossRefPubMedGoogle Scholar
  48. 48.
    Xia Z, DePierre JW, Nässberger L (1996) Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology 34(1):27–37CrossRefPubMedGoogle Scholar
  49. 49.
    Maes M, Song C, Lin AH, Bonaccorso S, Kenis G, De Jongh R, Bosmans E, Scharpé S (1999) Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 20(4):370–379CrossRefPubMedGoogle Scholar
  50. 50.
    Kenis G, Maes M (2002) Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol 5(4):401–412CrossRefPubMedGoogle Scholar
  51. 51.
    Hannestad J, DellaGioia N, Bloch M (2011) The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36(12):2452–2459CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Munzer A, Sack U, Mergl R, Schönherr J, Petersein C, Bartsch S, Kirkby KC, Bauer K, Himmerich H (2013) Impact of antidepressants on cytokine production of depressed patients in vitro. Toxins (Basel) 5(11):2227–2240CrossRefGoogle Scholar
  53. 53.
    Maes M, Berk M, Goehler L, Song C, Anderson G, Gałecki P (2012) Leonard B (2012) Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med 10:66CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Maes M, Mihaylova I, Ruyter MD, Kubera M, Bosmans E (2007) The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression—and other conditions characterized by tryptophan depletion induced by inflammation. Neuroendocrinol Lett 28(6):826–831PubMedGoogle Scholar
  55. 55.
    Maes M, Leonard BE, Myint AM, Kubera M, Verkerk R (2011) 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 35(3):702–721CrossRefPubMedGoogle Scholar
  56. 56.
    Hernansanz-Agustín P, Izquierdo-Álvarez A, García-Ortiz A, Ibiza S, Serrador JM, Martínez-Ruiz A (2013) Nitrosothiols in the immune system: signaling and protection. Antioxid Redox Signal 18(3):288–308CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Moylan S, Berk M, Dean OM, Samuni Y, Williams LJ, O’Neil A, Hayley AC, Pasco JA, Anderson G, Jacka FN, Maes M (2014) Oxidative & nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev 45:46–62CrossRefPubMedGoogle Scholar
  58. 58.
    García-Bueno B, Madrigal JL, Pérez-Nievas BG, Leza JC (2008) Stress mediators regulate brain prostaglandin synthesis and peroxisome proliferator-activated receptor-gamma activation after stress in rats. Endocrinology 149:1969–1978CrossRefPubMedGoogle Scholar
  59. 59.
    García-Bueno B, Caso JR, Leza JC (2008) Stress as a neuroinflammatory condition in brain: damaging and protective mechanisms. Neurosci Biobehav Rev 32:1136–1151CrossRefPubMedGoogle Scholar
  60. 60.
    García-Bueno B, Caso JR, Pérez-Nievas BG, Lorenzo P, Leza JC (2007) Effects of peroxisome proliferator-activated receptor gamma agonists on brain glucose and glutamate transporters after stress in rats. Neuropsychopharmacology 32:1251–1260CrossRefPubMedGoogle Scholar
  61. 61.
    Maes M (2012) Targeting cyclooxygenase-2 in depression is not a viable therapeutic approach and may even aggravate the pathophysiology underpinning depression. Metab Brain Dis 27(4):405–413CrossRefPubMedGoogle Scholar
  62. 62.
    Galecki P, Galecka E, Maes M, Chamielec M, Orzechowska A, Bobin’ska K, Lewin’ski A, Szemraj J (2012) The expression of genes encoding for COX-2, MPO, iNOS, and sPLA2-IIA in patients with recurrent depressive disorder. J Affect Disord 138(3):360–366CrossRefPubMedGoogle Scholar
  63. 63.
    Sepanjnia K, Modabbernia A, Ashrafi M, Modabbernia MJ, Akhondzadeh S (2012) Pioglitazone adjunctive therapy for moderate-to-severe major depressive disorder: randomized double-blind placebo-controlled trial. Neuropsychopharmacology 37:2093–2100CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    O’Neil A, Sanna L, Redlich C, Sanderson K, Jacka F, Williams LJ, Pasco JA (2012) Berk M (2012) The impact of statins on psychological wellbeing: a systematic review and meta-analysis. BMC Med 10:154CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Pasco JA, Jacka FN, Williams LJ, Henry MJ, Nicholson GC, Kotowicz MA, Berk M (2010) Clinical implications of the cytokine hypothesis of depression: the association between use of statins and aspirin and the risk of major depression. Psychother Psychosom 79(5):323–325CrossRefPubMedGoogle Scholar
  66. 66.
    Stafford L, Berk M (2011) The use of statins after a cardiac intervention is associated with reduced risk of subsequent depression: proof of concept for the inflammatory and oxidative hypotheses of depression? J Clin Psychiatry 72(9):1229–1235CrossRefPubMedGoogle Scholar
  67. 67.
    Ghanizadeh A, Hedayati A (2013) Augmentation of fluoxetine with lovastatin for treating major depressive disorder, a randomized double-blind placebo controlled-clinical trial. Depress Anxiety 30(11):1084–1088CrossRefPubMedGoogle Scholar
  68. 68.
    Kang J-H, Kao L-T, Lin H-C, Tsai M-C, Chung S-D (2014) Statin Use Increases the Risk of Depressive Disorder in Stroke Patients: A Population-Based Study. J Neurol Sci 2014; Available online 18 November 2014Google Scholar
  69. 69.
    Tuccori M, Montagnani S, Mantarro S, Capogrosso-Sansone A, Ruggiero E, Saporiti A, Antonioli L, Fornai M, Blandizzi C (2014) Neuropsychiatric adverse events associated with statins: epidemiology, pathophysiology, prevention and management. CNS Drugs 28(3):249–272CrossRefPubMedGoogle Scholar
  70. 70.
    Fernandes GH, Zanoteli E, Shinjo SK (2014) Statin-associated necrotizing autoimmune myopathy. Mod Rheumatol 24(5):862–864CrossRefPubMedGoogle Scholar
  71. 71.
    Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (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(1):31–41CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Cimaz R (2008) Lehman T (2008) Pediatrics in systemic autoimmune diseases. In: Asherson RA (ed) Handbook of Systemic Autoimmune Diseases, volume 6. Elsevier, AmsterdamGoogle Scholar
  73. 73.
    Saraceno R, Faleri S, Ruzzetti M, Centonze D, Chimenti S (2012) Prevalence and management of panic attacks during infliximab infusion in psoriatic patients. Dermatology 225:236–241CrossRefPubMedGoogle Scholar
  74. 74.
    Eshuis EJ, Magnin KM, Stokkers PC, Bemelman WA, Bartelsman J (2010) Suicide attempt in ulcerative colitis patient after 4 months of infliximab therapy—a case report. J Crohn’s Colitis 4(5):591–593CrossRefGoogle Scholar
  75. 75.
    Elisa B, Beny L (2010) Induction of manic switch by the tumour necrosis factor-alpha antagonist infliximab. Psychiatry Clin Neurosci 64(4):442–443CrossRefPubMedGoogle Scholar
  76. 76.
    Charles PJ, Smeenk RJ, De Jong J, Feldmann M, Maini RN (2000) Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials. Arthritis Rheum 43(11):2383–2390CrossRefPubMedGoogle Scholar
  77. 77.
    Dodd S, Maes M, Anderson G, Dean OM, Moylan S, Berk M (2013) Putative neuroprotective agents in neuropsychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 42:135–145CrossRefPubMedGoogle Scholar
  78. 78.
    Lai J, Moxey A, Nowak G, Vashum K, Bailey K, McEvoy M (2012) The efficacy of zinc supplementation in depression: systematic review of randomised controlled trials. J Affect Disord 136(1–2):e31–e39CrossRefPubMedGoogle Scholar
  79. 79.
    Magalhães PV, Dean OM, Bush AI, Copolov DL, Malhi GS, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2011) N-acetylcysteine for major depressive episodes in bipolar disorder. Rev Bras Psiquiatr 33(4):374–378CrossRefPubMedGoogle Scholar
  80. 80.
    Lopresti AL, Maes M, Maker GL, Hood SD, Drummond PD (2014) Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study. J Affect Disord 167:368–375CrossRefPubMedGoogle Scholar
  81. 81.
    Song C, Zhang XY, Manku M (2009) Increased phospholipase A2 activity and inflammatory response but decreased nerve growth factor expression in the olfactory bulbectomized rat model of depression: effects of chronic ethyl-eicosapentaenoate treatment. J Neurosci 29(1):14–22CrossRefPubMedGoogle Scholar
  82. 82.
    Leonard B, Maes M (2012) 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 36(2):764–785CrossRefPubMedGoogle Scholar
  83. 83.
    Schiebinger L, Schraudner M (2011) Interdisciplinary approaches to achieving gendered innovations in science, medicine, and engineering. Interdisc Sci Rev 36:154–167CrossRefGoogle Scholar
  84. 84.
    Vodovotz Y, Csete M, Bartels J, Chang S, An G (2008) Translational systems biology of inflammation. PLoS Comput Biol 4(4), e1000014CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Aderem A, Smith KD (2004) A systems approach to dissecting immunity and inflammation. Semin Immunol 16(1):55–67CrossRefPubMedGoogle Scholar
  86. 86.
    Cesario A, Auffray C, Agusti A, Apolone G, Balling R, Barbanti P, Bellia A, Boccia S, Bousquet J, Cardaci V, Cazzola M, Dall’Armi V, Daraselia N, Ros LD, Bufalo AD, Ducci G, Ferri L, Fini M, Fossati C, Gensini G, Granone PM, Kinross J, Lauro D, Cascio GL, Lococo F, Lococo A, Maier D, Marcus F, Margaritora S, Marra C, Minati G, Neri M, Pasqua F, Pison C, Pristipino C, Roca J, Rosano G, Rossini PM, Russo P, Salinaro G, Shenhar S, Soreq H, Sterk PJ, Stocchi F, Torti M, Volterrani M, Wouters EF, Frustaci A, Bonassi S (2014) A systems medicine clinical platform for understanding and managing non-communicable diseases. Curr Pharm Des 20(38):5945–5956CrossRefPubMedGoogle Scholar
  87. 87.
    Antony PM, Balling R, Vlassis N (2012) From systems biology to systems biomedicine. Curr Opin Biotechnol 23(4):604–608CrossRefPubMedGoogle Scholar
  88. 88.
    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504Google Scholar
  89. 89.
    Chindelevitch L, Ziemek D, Enayetallah A, Randhawa R, Sidders B, Brockel C, Huang ES (2012) Causal reasoning on biological networks: interpreting transcriptional changes. Bioinformatics 28(8):1114–1121CrossRefPubMedGoogle Scholar
  90. 90.
    Feiglin A, Hacohen A, Sarusi A, Fisher J, Unger R, Ofran Y (2012) Static network structure can be used to model the phenotypic effects of perturbations in regulatory networks. Bioinformatics 28(21):2811–2818CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Michael Maes
    • 1
    • 2
    • 3
    • 15
  • Gabriel Nowak
    • 4
    • 5
  • Javier R. Caso
    • 6
  • Juan Carlos Leza
    • 6
  • Cai Song
    • 7
    • 8
  • Marta Kubera
    • 9
  • Hans Klein
    • 10
  • Piotr Galecki
    • 11
  • Cristiano Noto
    • 12
  • Enrico Glaab
    • 13
  • Rudi Balling
    • 13
  • Michael Berk
    • 1
    • 14
  1. 1.IMPACT Research CenterDeakin UniversityGeelongAustralia
  2. 2.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  3. 3.Health Sciences Graduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  4. 4.Department of PharmacobiologyJagiellonian University Medical CollegeKrakówPoland
  5. 5.Department of Neurobiology, Institute of PharmacologyPolish Academy of SciencesKrakówPoland
  6. 6.Department of Pharmacology, Faculty of MedicineUniversity Complutense, Centro de Investigación Biomédica en Salud Mental (CIBERSAM) & Instituto de Investigación Sanitaria Hospital 12 de OctubreMadridSpain
  7. 7.Department of Psychology and NeuroscienceDalhousie UniversityHalifaxCanada
  8. 8.Research Institute for Marine Nutrition and DrugsGuangdong Ocean UniversityZhanjiangChina
  9. 9.Department of Experimental Neuroendocrinology, Institute of PharmacologyPolish Academy of ScienceKrakowPoland
  10. 10.Department of PsychiatryUniversity of GroningenGroningenThe Netherlands
  11. 11.Department of Adult PsychiatryMedial University of ŁódźŁódźPoland
  12. 12.Department of PsychiatryUniversidade Federal de São Paulo (UNIFESP)Sao PauloBrazil
  13. 13.Luxembourg Centre for Systems BiomedicineUniversity of LuxemburgEsch-sur-AlzetteLuxembourg
  14. 14.Orygen, The National Centre of Excellence in Youth Mental Health, Department of Psychiatry and The Florey Institute of Neuroscience and Mental HealthThe University of MelbourneParkvilleAustralia
  15. 15.IMPACT Strategic Research Center, Barwon HealthDeakin UniversityGeelongAustralia

Personalised recommendations