Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Antoine Yrondi, Bruno Aouizerate, Wissam El-Hage, Fanny Moliere, Claire Thalamas, Nicolas Delcourt, Marie Sporer, Simon Taib, Laurent Schmitt, Nicolas Arlicot, Deborah Meligne, Agnes Sommet, Anne S Salabert, Sebastien Guillaume, Philippe Courtet, Florence Galtier, Denis Mariano-Goulart, Nicolas Menjot De Champfleur, Emmanuelle Le Bars, Thomas Desmidt, Mathieu Lemaire, Vincent Camus, Maria J Santiago-Ribeiro, Jean P Cottier, Philippe Fernandez, Marie Meyer, Vincent Dousset, Olivier Doumy, Didier Delhaye, Lucile Capuron, Marion Leboyer, Emmanuel Haffen, Patrice Péran, Pierre Payoux, Christophe Arbus, Antoine Yrondi, Bruno Aouizerate, Wissam El-Hage, Fanny Moliere, Claire Thalamas, Nicolas Delcourt, Marie Sporer, Simon Taib, Laurent Schmitt, Nicolas Arlicot, Deborah Meligne, Agnes Sommet, Anne S Salabert, Sebastien Guillaume, Philippe Courtet, Florence Galtier, Denis Mariano-Goulart, Nicolas Menjot De Champfleur, Emmanuelle Le Bars, Thomas Desmidt, Mathieu Lemaire, Vincent Camus, Maria J Santiago-Ribeiro, Jean P Cottier, Philippe Fernandez, Marie Meyer, Vincent Dousset, Olivier Doumy, Didier Delhaye, Lucile Capuron, Marion Leboyer, Emmanuel Haffen, Patrice Péran, Pierre Payoux, Christophe Arbus

Abstract

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4-20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance. Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group-patients with current MDD (n = 20), (ii) remitted depressed group-patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups. Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice. Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=1.

Keywords: DPA-714; TSPO; cytokines; depression; depressive disorder; inflammation; neuroinflammation.

References

    1. Sartorius N. The economic and social burden of depression. J Clin Psychiatry (2001) 62(Suppl. 15):8–11.
    1. Bakish D. New standard of depression treatment: remission and full recovery. J Clin Psychiatry (2001) 62(Suppl. 26):5–9.
    1. Bonicatto SC, Dew MA, Zaratiegui R, Lorenzo L, Pecina P. Adult outpatients with depression: worse quality of life than in other chronic medical diseases in Argentina. Soc Sci Med. 1982 (2001) 52:911–9. 10.1016/S0277-9536(00)00192-1
    1. IsHak WW, Greenberg JM, Balayan K, Kapitanski N, Jeffrey J, Fathy H, et al. . Quality of life: the ultimate outcome measure of interventions in major depressive disorder. Harv Rev Psychiatry (2011) 19:229–39. 10.3109/10673229.2011.614099
    1. Papakostas GI, Petersen T, Mahal Y, Mischoulon D, Nierenberg AA, Fava M. Quality of life assessments in major depressive disorder: a review of the literature. Gen Hosp Psychiatry (2004) 26:13–7. 10.1016/j.genhosppsych.2003.07.004
    1. Consoli SM, Depression and Organic Diseases Study . [Depression and associated organic pathologies, a still under-estimated comorbidity. Results of the DIALOGUE study]. Presse Méd Paris Fr 1983 (2003) 32:10–21.
    1. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. . Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry (2006) 163:1905–17. 10.1176/ajp.2006.163.11.1905
    1. Malhi GS, Parker GB, Crawford J, Wilhelm K, Mitchell PB. Treatment-resistant depression: resistant to definition? Acta Psychiatr Scand. (2005) 112:302–9. 10.1111/j.1600-0447.2005.00602.x
    1. McIntyre RS, Filteau M-J, Martin L, Patry S, Carvalho A, Cha DS, et al. . Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. (2014) 156:1–7. 10.1016/j.jad.2013.10.043
    1. Schildkraut JJ. The catecholamine hypothesis of affective disorders. A review of supporting evidence. Int J Psychiatry (1967) 4:203–17.
    1. Schildkraut JJ, Schanberg SM, Breese GR, Kopin IJ. Norepinephrine metabolism and drugs used in the affective disorders: a possible mechanism of action. Am J Psychiatry (1967) 124:600–8. 10.1176/ajp.124.5.600
    1. Delgado PL. Monoamine depletion studies: implications for antidepressant discontinuation syndrome. J Clin Psychiatry (2006) 67(Suppl. 4):22–6.
    1. Capuron L, Castanon N. Role of inflammation in the development of neuropsychiatric symptom domains: evidence and mechanisms. Curr Top Behav Neurosci. (2017) 31:31–44. 10.1007/7854_2016_14
    1. Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. (2011) 130:226–38. 10.1016/j.pharmthera.2011.01.014
    1. Andersson NW, Gustafsson LN, Okkels N, Taha F, Cole SW, Munk-Jørgensen P, et al. . Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study. Psychol Med. (2015) 45:3559–69. 10.1017/S0033291715001488
    1. Imran MY, Saira Khan EA, Ahmad NM, Farman Raja S, Saeed MA, Ijaz Haider I. Depression in Rheumatoid Arthritis and its relation to disease activity. Pak J Med Sci. (2015) 31:393–7. 10.12669/pjms.312.6589
    1. Margaretten M, Julian L, Katz P, Yelin E. Depression in patients with rheumatoid arthritis: description, causes and mechanisms. Int J Clin Rheumatol. (2011) 6:617–23. 10.2217/IJR.11.6
    1. Hider SL, Tanveer W, Brownfield A, Mattey DL, Packham JC. Depression in RA patients treated with anti-TNF is common and under-recognized in the rheumatology clinic. Rheumatology (2009) 48:1152–4. 10.1093/rheumatology/kep170
    1. Valkanova V, Ebmeier KP, Allan CL. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord. (2013) 150:736–44. 10.1016/j.jad.2013.06.004
    1. Wium-Andersen MK, Ørsted DD, Nielsen SF, Nordestgaard BG. Elevated C-reactive protein levels, psychological distress, and depression in 73, 131 individuals. JAMA Psychiatry (2013) 70:176–84. 10.1001/2013.jamapsychiatry.102
    1. Zalli A, Jovanova O, Hoogendijk WJG, Tiemeier H, Carvalho LA. Low-grade inflammation predicts persistence of depressive symptoms. Psychopharmacology (2016) 233:1669–178. 10.1007/s00213-015-3919-9
    1. Vogelzangs N, de Jonge P, Smit JH, Bahn S, Penninx BW. Cytokine production capacity in depression and anxiety. Transl Psychiatry (2016) 6:e825. 10.1038/tp.2016.92
    1. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry (2009) 65:732–41. 10.1016/j.biopsych.2008.11.029
    1. Miller AH. Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun. (2009) 23:149–58. 10.1016/j.bbi.2008.08.006
    1. Graeber MB, Tetzlaff W, Streit WJ, Kreutzberg GW. Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neurosci Lett. (1988) 85:317–21.
    1. Graeber MB, Kreutzberg GW. Delayed astrocyte reaction following facial nerve axotomy. J Neurocytol. (1988) 17:209–20.
    1. Graeber MB, Streit WJ. Microglia: immune network in the CNS. Brain Pathol. (1990) 1:2–5.
    1. van Rossum D, Hanisch U-K. Microglia. Metab Brain Dis. (2004) 19:393–411.
    1. Hanisch U-K. Microglia as a source and target of cytokines. Glia (2002) 40:140–55. 10.1002/glia.10161
    1. Takahashi A, Flanigan ME, McEwen BS, Russo SJ. Aggression, Social Stress, and the Immune System in Humans and Animal Models. Front Behav Neurosci. (2018) 12:56. 10.3389/fnbeh.2018.00056
    1. Turecki G, Meaney MJ. Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review. Biol Psychiatry (2016) 79:87–96. 10.1016/j.biopsych.2014.11.022
    1. Labonté B, Suderman M, Maussion G, Navaro L, Yerko V, Mahar I, et al. . Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry (2012) 69:722–31. 10.1001/archgenpsychiatry.2011.2287
    1. Zhang TY, Labonté B, Wen XL, Turecki G, Meaney MJ. Epigenetic mechanisms for the early environmental regulation of hippocampal glucocorticoid receptor gene expression in rodents and humans. Neuropsychopharmacology (2013) 38:111–23. 10.1038/npp.2012.149
    1. Gong Q, He Y. Depression, neuroimaging and connectomics: a selective overview. Biol Psychiatry (2015) 77:223–35. 10.1016/j.biopsych.2014.08.009
    1. Meier TB, Drevets WC, Wurfel BE, Ford BN, Morris HM, Victor TA, et al. . Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder. Brain Behav Immun. (2016) 53:39–48. 10.1016/j.bbi.2015.11.003
    1. Savitz J, Dantzer R, Meier TB, Wurfel BE, Victor TA, McIntosh SAF, et al. . Activation of the kynurenine pathway is associated with striatal volume in major depressive disorder. Psychoneuroendocrinology (2015) 62:54–8. 10.1016/j.psyneuen.2015.07.609
    1. Dannlowski U, Ohrmann P, Bauer J, Kugel H, Arolt V, Heindel W, et al. . Amygdala reactivity to masked negative faces is associated with automatic judgmental bias in major depression: a 3 T fMRI study. J Psychiatry Neurosci. (2007) 32:423–9.
    1. Fales CL, Barch DM, Rundle MM, Mintun MA, Snyder AZ, Cohen JD, et al. . Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biol Psychiatry (2008) 63:377–84. 10.1016/j.biopsych.2007.06.012
    1. Fu CHY, Mourao-Miranda J, Costafreda SG, Khanna A, Marquand AF, Williams SCR, et al. . Pattern classification of sad facial processing: toward the development of neurobiological markers in depression. Biol Psychiatry (2008) 63:656–62. 10.1016/j.biopsych.2007.08.020
    1. Keedwell PA, Andrew C, Williams SCR, Brammer MJ, Phillips ML. A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals. Biol Psychiatry (2005) 58:495–503. 10.1016/j.biopsych.2005.04.035
    1. Surguladze S, Brammer MJ, Keedwell P, Giampietro V, Young AW, Travis MJ, et al. . A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biol Psychiatry (2005) 57:201–9. 10.1016/j.biopsych.2004.10.028
    1. Felger JC, Li Z, Haroon E, Woolwine BJ, Jung MY, Hu X, et al. . Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol Psychiatry (2015) 21:1358–65. 10.1038/mp.2015.168
    1. Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, et al. . Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov. (2010) 9:971–88. 10.1038/nrd3295
    1. Hannestad J, DellaGioia N, Gallezot J-D, Lim K, Nabulsi N, Esterlis I, et al. . The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: a [11C]PBR28 PET study. Brain Behav Immun. (2013) 33:131–8. 10.1016/j.bbi.2013.06.010
    1. Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G, et al. . Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry (2015) 72:268–75. 10.1001/jamapsychiatry.2014.2427
    1. Arlicot N, Vercouillie J, Ribeiro M-J, Tauber C, Venel Y, Baulieu J-L, et al. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol. (2012) 39:570–8. 10.1016/j.nucmedbio.2011.10.012
    1. Hamelin L, Lagarde J, Dorothée G, Leroy C, Labit M, Comley RA, et al. . Early and protective microglial activation in Alzheimer′s disease: a prospective study using 18F-DPA-714 PET imaging. Brain J Neurol. (2016) 139:1252–64. 10.1093/brain/aww017
    1. Lavisse S, García-Lorenzo D, Peyronneau M-A, Bodini B, Thiriez C, Kuhnast B, et al. Optimized quantification of translocator protein radioligand 18F-DPA-714 uptake in the brain of genotyped healthy volunteers. J Nucl Med. (2015) 56:1048–54. 10.2967/jnumed.115.156083
    1. Lyoo CH, Ikawa M, Liow J-S, Zoghbi SS, Morse CL, Pike VW, et al. . Cerebellum can serve as a pseudo-reference region in alzheimer disease to detect neuroinflammation measured with PET radioligand binding to translocator protein. J Nucl Med. (2015) 56:701–6. 10.2967/jnumed.114.146027
    1. Yrondi A, Bennabi D, Haffen E, Garnier M, Bellivier F, Bourgerol T, et al. . Significant need for a french network of expert centers enabling a better characterization and management of treatment-resistant depression (fondation fondamental). Front Psychiatry (2017) 8:244. 10.3389/fpsyt.2017.00244
    1. Zimmerman M, Posternak MA, Chelminski I. Derivation of a definition of remission on the Montgomery-Asberg depression rating scale corresponding to the definition of remission on the Hamilton rating scale for depression. J Psychiatr Res. (2004) 38:577–82. 10.1016/j.jpsychires.2004.03.007
    1. Lesur A, Bonnet D, Vicaut E, Lempérière T. [Tyrer′s Brief Scale for Anxiety used with outpatients. First validation in the French language]. L′Encéphale (1989) 15:535–42.
    1. Tyrer P, Owen RT, Cicchetti DV. The brief scale for anxiety: a subdivision of the comprehensive psychopathological rating scale. J Neurol Neurosurg Psychiatry (1984) 47:970–5.
    1. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. . The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry (2011) 168:1266–77. 10.1176/appi.ajp.2011.10111704
    1. Mabrouk R, Strafella AP, Knezevic D, Ghadery C, Mizrahi R, Gharehgazlou A, et al. Feasibility study of TSPO quantification with [18F]FEPPA using population-based input function. PLoS ONE (2017) 12:e0177785 10.1371/journal.pone.0177785
    1. Kuhnast B, Damont A, Hinnen F, Catarina T, Demphel S, Le Helleix S, et al. [18F]DPA-714, [18F]PBR111 and [18F]FEDAA1106-selective radioligands for imaging TSPO 18 kDa with PET: automated radiosynthesis on a TRACERLAb FX-FN synthesizer and quality controls. Appl Radiat Isot Data Instrum Methods Use Agric Ind Med. (2012) 70:489–97. 10.1016/j.apradiso.2011.10.015
    1. Wilson AA, Garcia A, Parkes J, McCormick P, Stephenson KA, Houle S, et al. . Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors. Nucl Med Biol. (2008) 35:305–14. 10.1016/j.nucmedbio.2007.12.009
    1. James ML, Fulton RR, Vercoullie J, Henderson DJ, Garreau L, Chalon S, et al. . DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med. (2008) 49:814–22. 10.2967/jnumed.107.046151
    1. Peyronneau M-A, Saba W, Goutal S, Damont A, Dolle F, Kassiou M, et al. Metabolism and Quantification of [18F]DPA-714, a New TSPO Positron Emission Tomography Radioligand. Drug Metab Dispos. (2012) 41:122–31. 10.1124/dmd.112.046342
    1. Kenk M, Selvanathan T, Rao N, Suridjan I, Rusjan P, Remington G, et al. Imaging neuroinflammation in gray and white matter in schizophrenia: an in-vivo PET study with [18F]-FEPPA. Schizophr Bull. (2015) 41:85–93. 10.1093/schbul/sbu157
    1. Koshimori Y, Ko J-H, Mizrahi R, Rusjan P, Mabrouk R, Jacobs MF, et al. . Imaging striatal microglial activation in patients with parkinson′s disease. PLoS ONE (2015) 10:e0138721. 10.1371/journal.pone.0138721
    1. Suridjan I, Rusjan PM, Voineskos AN, Selvanathan T, Setiawan E, Strafella AP, et al. Neuroinflammation in healthy aging: a PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [(18)F]-FEPPA. Neuroimage (2014) 84:868–75. 10.1016/j.neuroimage.2013.09.021
    1. Fan Z, Harold D, Pasqualetti G, Williams J, Brooks DJ, Edison P. Can studies of neuroinflammation in a TSPO genetic subgroup (HAB or MAB) be applied to the entire AD cohort? J Nucl Med. (2015) 56:707–13. 10.2967/jnumed.114.149443
    1. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. . A meta-analysis of cytokines in major depression. Biol Psychiatry (2010) 67:446–57. 10.1016/j.biopsych.2009.09.033
    1. Lecrubier Y, Sheehan D, Weiller E, Amorim P, Bonora I, Harnett Sheehan K, et al. A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry (1997) 12:224–31. 10.1016/S0924-9338(97)83296-8
    1. Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(-)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab. (1990) 10:740–47. 10.1038/jcbfm.1990.127
    1. Eustache P, Nemmi F, Saint-Aubert L, Pariente J, Péran P. Multimodal magnetic resonance imaging in alzheimer′s disease patients at prodromal stage. J Alzheimers Dis. (2016) 50:1035–50. 10.3233/JAD-150353
    1. Péran P, Cherubini A, Luccichenti G, Hagberg G, Démonet J-F, Rascol O, et al. . Volume and iron content in basal ganglia and thalamus. Hum Brain Mapp. (2009) 30:2667–75. 10.1002/hbm.20698
    1. Cherubini A, Péran P, Caltagirone C, Sabatini U, Spalletta G. Aging of subcortical nuclei: microstructural, mineralization and atrophy modifications measured in vivo using MRI. Neuroimage (2009) 48:29–36. 10.1016/j.neuroimage.2009.06.035
    1. Barbagallo G, Sierra-Peña M, Nemmi F, Traon AP-L, Meissner WG, Rascol O, et al. . Multimodal MRI assessment of nigro-striatal pathway in multiple system atrophy and Parkinson disease. Mov Disord. (2016) 31:325–34. 10.1002/mds.26471
    1. Nemmi F, Saint-Aubert L, Adel D, Salabert A-S, Pariente J, Barbeau EJ, et al. . Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer′s disease patients and healthy subjects. Eur J Nucl Med Mol Imaging (2014) 41:1408–18. 10.1007/s00259-014-2728-4
    1. Lépine J-P, Briley M. The increasing burden of depression. Neuropsychiatr Dis Treat. (2011) 7:3–7. 10.2147/NDT.S19617
    1. Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. (1996) 19:179–200.
    1. Hamon M, Blier P. Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry (2013) 45:54–63. 10.1016/j.pnpbp.2013.04.009
    1. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. (2016) 16:22–34. 10.1038/nri.2015.5
    1. Kim Y-K, Na K-S, Myint A-M, Leonard BE. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry (2016) 64:277–84. 10.1016/j.pnpbp.2015.06.008
    1. Rosenblat JD, Cha DS, Mansur RB, McIntyre RS. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry (2014) 53:23–34. 10.1016/j.pnpbp.2014.01.013
    1. Wohleb ES, Franklin T, Iwata M, Duman RS. Integrating neuroimmune systems in the neurobiology of depression. Nat Rev Neurosci. (2016) 17:497–511. 10.1038/nrn.2016.69
    1. Osimo EF, Cardinal RN, Jones PB, Khandaker GM. Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: an electronic health record-based study. Psychoneuroendocrinology (2018) 91:226–34. 10.1016/j.psyneuen.2018.02.031
    1. Fond G, Hamdani N, Kapczinski F, Boukouaci W, Drancourt N, Dargel A, et al. . Effectiveness and tolerance of anti-inflammatory drugs′ add-on therapy in major mental disorders: a systematic qualitative review. Acta Psychiatr Scand. (2014) 129:163–79. 10.1111/acps.12211
    1. Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology (2011) 36:2452–9. 10.1038/npp.2011.132
    1. O′Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res. (2007) 41:326–31. 10.1016/j.jpsychires.2006.05.013
    1. Eller T, Vasar V, Shlik J, Maron E. Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry (2008) 32:445–50. 10.1016/j.pnpbp.2007.09.015
    1. Cattaneo A, Gennarelli M, Uher R, Breen G, Farmer A, Aitchison KJ, et al. . Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline “predictors” and longitudinal “targets.” Neuropsychopharmacology (2013) 38:377–85. 10.1038/npp.2012.191
    1. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, 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) 70:31–41. 10.1001/2013.jamapsychiatry.4
    1. Abbasi S-H, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S. Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. J Affect Disord. (2012) 141:308–14. 10.1016/j.jad.2012.03.033
    1. Yrondi A, Sporer M, Péran P, Schmitt L, Arbus C, Sauvaget A. Electroconvulsive therapy, depression, the immune system and inflammation: a systematic review. Brain Stimul Basic Transl Clin Res Neuromodulation (2017) 11:29–51. 10.1016/j.brs.2017.10.013
    1. Jokela M, Virtanen M, Batty GD, Kivimäki M. Inflammation and specific symptoms of depression. JAMA Psychiatry (2016) 73:87–8. 10.1001/jamapsychiatry.2015.1977
    1. Goldsmith DR, Haroon E, Woolwine BJ, Jung MY, Wommack EC, Harvey PD, et al. . Inflammatory markers are associated with decreased psychomotor speed in patients with major depressive disorder. Brain Behav Immun. (2016) 56:281–8. 10.1016/j.bbi.2016.03.025
    1. Köhler-Forsberg O, Buttenschøn HN, Tansey KE, Maier W, Hauser J, Dernovsek MZ, et al. . Association between C-reactive protein (CRP) with depression symptom severity and specific depressive symptoms in major depression. Brain Behav Immun. (2017) 62:344–50. 10.1016/j.bbi.2017.02.020
    1. Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, et al. . Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: a positron emission tomography study. Biol Psychiatry (2018) 83:61–9. 10.1016/j.biopsych.2017.08.005

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi