Tijdens een griepje heb je last van hoofdpijn, koorts, hoesten en een zere keel. Daarnaast heb je geen zin om te eten, ben je moe en voel je je lusteloos. We noemen dit het sickness syndrome. Deze veranderingen worden veroorzaakt door pro-inflammatoire cytokinen die worden afgegeven door het immuunsysteem en ervoor zorgen dat je je terugtrekt. Vroeger in de oertijd was dit een goede aanpassing, geen energie steken in vechten of vluchten, maar je gedeisd houden en alle energie gebruiken voor een snel herstel. De symptomen lusteloosheid, oververmoeidheid en verstoord eetpatroon komen sterk overeen met de symptomen van een depressie. Het komt dan ook niet als een verrassing dat uit steeds meer onderzoek blijkt dat patiënten met ernstige infectieziekten of chronische ontstekingsziekten een veel hogere kans hebben op het krijgen van een depressie. Sinds kort begrijpen we beter waardoor dit komt.
Depressie is een complexe aandoening waaraan wereldwijd 350 miljoen mensen lijden. Daarvan zien 500.000 depressieve patiënten geen andere uitweg dan zelfdoding. In Nederland hebben jaarlijks meer dan 800.000 mensen een depressieve stoornis. Naast al het persoonlijke leed, ook van familie en vrienden, is depressie de grootste oorzaak van arbeidsverzuim. Dit kost de Nederlandse samenleving meer dan 1,5 miljard euro per jaar.
Abstract
There is a growing body of evidence that suggests that chronic inflammation can increase the risk to develop major depression. During chronic inflammation increased levels of proinflammatory cytokines can affect the emotional brain via different routes.
For example:
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increased levels of indoleamine 2,3-dioxygenase (IDO) are responsible for lower tryptophane levels and consequently lower serotonin levels in the brain;
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due to an increase in reactive oxygen species (ROS) the availability of the co-factor BH4 will decrease, since BH4 stimulates the rate-limiting enzymes (tryptophane-hydroxylase and tyrosine-hydroxylase) for the synthesis of monoamines, both serotonin, melatonin, dopamine and norepinephrine will decrease;
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and increased levels of pro-inflammatory cytokines stimulate the p38 MAPK pathway and MEK pathway, thereby enhancing SERT, DAT and NET trafficking and function, respectively.
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Literatuur
Banks, W.A. & Erickson, M.A. (2010). The blood-brain barrier and immune function and dysfunction. Neurobiological Disorders, 37, 1, 26–32.
Barbierato, M., Facci, L., Argentini, C., Marinelli, C., Skaper, S.D. & Giusti P. (2013). Astrocyte-Microglia Cooperation in the Expression of a Pro-Inflammatory Phenotype. CNS & Neurological Disorders Drug Targets. (Epub ahead of print)
Benros, M.E., Waltoft, B.L., Nordentoft, M., Ostergaard, S.D., Eaton, W.W., Krogh, J. & Mortensen, P.B. (2013). Autoimmune Diseases and Severe Infections as Risk Factors for Mood Disorders: A Nationwide Study. JAMA Psychiatry, 12, 1–9.
Bluthé, R.M., Walter, V., Parnet, P., Layé, S., Lestage, J., Verrier, D., Poole, S., Stenning, B.E., Kelley, K.W. & Dantzer, R. (1994). Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. Comptes rendus de l’Académie des sciences. Série III, Sciences de la vie, 317, 6, 499–503.
Capuron, L., Pagnoni, G., Drake, D.F., Woolwine, B.J., Spivey, J.R., Crowe, R.J., Votaw, J.R., Goodman, M.M. & Miller, A.H. (2012). Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration. Archives of General Psychiatry, 69, 10, 1044–1053.
Chung, I.Y. & Benveniste, E.N. (1990). Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFNgamma, and IL-1 beta. Journal of Immunology, 144, 8, 2999–3007.
Corona, A.W., Norden, D.M., Skendelas, J.P., Huang, Y., O’Connor, J.C., Lawson, M., Dantzer, R., Kelley, K.W. & Godbout, J.P. (2013). Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor (CX(3)CR1)- deficient mice. Brain Behavior and Immununity, 31,134–142.
D’Mello, C., Le, T. & Swain, M.G. (2009). Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. Journal of Neuroscience, 29, 7, 2089–2102.
Dantzer, R., O’Connor, J.C., Lawson, M.A. & Kelley, K.W. (2011). Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology. 36, 3, 426–436.
Felger, J.C. & Miller, A.H. (2012). Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise. Frontiers in Neuroendocrinology, 33, 3, 315–327.
Hartwell, K.J., Moran-Santa Maria, M.M., Twal, W.O., Shaftman, S., DeSantis, S.M., McRae-Clark, A.L. & Brady, K.T. (2013). Association of elevated cytokines with childhood adversity in a sample of healthy adults. Journal of Psychiatry Research, 47,5, 604–610.
Heesch, F. van, Prins J., Konsman J.P., Westphal, K.G., Olivier, B., Kraneveld, A.D. & Korte, S.M. (2013). Lipopolysaccharide-induced anhedonia is abolished in male serotonin transporter knockout rats: an intracranial self-stimulation study. Brain Behavior and Immunity, 29, 98–103.
Kitagami, T., Yamada, K., Miura, H., Hashimoto, R., Nabeshima, T., & Ohta T. (2003). Mechanism of systemically injected interferonalpha impeding monoamine biosynthesis in rats: role of nitric oxide as a signal crossing the blood-brain barrier. Brain Research, 978,1-2, 104–114.
Konsman, J.P., Vigues, S., Mackerlova, L., Bristow, A. & Blomqvist, A. (2004). Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli. Journal of Comparative Neurology, 472, 1, 113–129.
Lieberman, A.P., Pitha, P.M., Shin, H.S. & Shin, M.L. (1989). Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proceedings of the National Academy of Sciences of the United States of America, 86, 16, 6348–6352.
Liu, Y., Ho, R.C. & Mak, A. (2012). Interleukin (IL)-6, tumor necrosis factor alpha (TNF-á) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. Journal of Affective Disorders, 139, 3, 230–239.
Matsumura, K. & Kobayashi, S. (2004). Signalling the brain in inflammation: the role of endothelial cells. Frontiers in Bioscience, 9, 2819–2826.
Palma, J.P., Kwon, D., Clipstone, N.A. & Kim, B.S. (2003). Infection with Theiler’s murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappa B activation: potential role for the initiation of demyelinating disease. Journal of Virology, 77, 11, 6322–6331.
Pan, W. & Kastin, A.J. (2003). Interactions of cytokines with the bloodbrain barrier: implications for feeding. Current Pharmaceutical Design, 9, 10, 827–831.
Pavlov, V.A. & Tracey, K.J. (2012). The vagus nerve and the inflammatory reflex–linking immunity and metabolism. Nature Reviews Endocrinology, 8,12,743–754.
Prins, J., Olivier, B. & Korte, S.M. (2011) Triple reuptake inhibitors for treating subtypes of major depressive disorder: the monoamine hypothesis revisited. Expert Opinion on Investigational Drugs, 20,8,1107–1130.
Raison, C.L., Demetrashvili, M., Capuron, L. & Miller, A.H. (2005). Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS Drugs, 19, 2, 105–123.
Raison, C.L., Rutherford, R.E., Woolwine, B.J., Shuo, C., Schettler, P., Drake, D.F., Haroon, E. & Miller, A.H. (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, 31–41.
Schöbitz, B., Voorhuis, D.A. & Kloet, E.R. de (1992). Localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. Neuroscience Letters, 136,2,189–192
Tuglu, C., Kara, S.H., Caliyurt, O., Vardar, E. & Abay, E. (2003). Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology (Berl),170, 4, 429–433.
Walker, J.R., Graff, L.A., Dutz, J.P. & Bernstein, C.N. 2011. Psychiatric disorders in patients with immune-mediated inflammatory diseases: prevalence, association with disease activity, and overall patient wellbeing. Journal of Rheumatology Supplement, 88, 31–35.
Wium-Andersen, M.K., Ørsted, D.D., Nielsen, S.F. & Nordestgaard, B.G. (2013). Elevated C-reactive protein levels, psychological distress, and depression in 73.131 individuals. JAMA Psychiatry, 70, 2, 176–184.
Zhu, C.B., Lindler, K.M., Owens, A.W., Daws, L.C., Blakely, R.D. & Hewlett, W.A. (2010). Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters. Neuropsychopharmacology, 35, 13, 2510–2520.
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Dr. S.M. Korte, UHD Neuroimmunofarmacologie; mw. F. van Heesch, AIO Focus en Massa; mw. dr. J. Prins, postdoc Neurofarmacologie; dr. R. Oosting, UHD Moleculaire Farmacologie; mw. dr. A.D. Kraneveld, UHD Neuroimmunofarmacologie; prof. dr. J. Garrsen, bijzonder hoogleraar Immunofarmacologie van voeding (Nutricia Research Foundation); prof. dr. B. Olivier, hoogleraar Psychofarmacologie. Allen zijn werkzaam bij het departement Farmaceutische Wetenschappen van de Faculteit Bètawetenschappen van de Universiteit Utrecht.
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Korte, M., van Heesch, F., Prins, J. et al. Overenthousiast immuunsysteem pakt ongelukkig uit. NEUROPRAXIS 17, 161–166 (2013). https://doi.org/10.1007/s12474-013-0030-z
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DOI: https://doi.org/10.1007/s12474-013-0030-z