CoChat
Sign Up
Cited by 237Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

Genetic Contributions of Inflammation to Depression

Open access
Barnes, Jacob, Mondelli, Valeria, Pariante, Carmine M·2017·Neuropsychopharmacology
DOI 10.1038/npp.2016.169PMC PMC5143493
Open this paper in CoChat — free accountOpen PDF

Abstract

This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a systematic review on all papers published between 2000 and 2016. Our results, based largely on case-control studies, suggest that common genetic variants and gene-expression pathways are involved in both immune activation and depression. The most replicated and relevant genetic variants include polymorphisms in the genes for interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2. Moreover, increased blood cytokines mRNA expression (especially of IL-1β) identifies patients that are less likely to respond to conventional antidepressants. However, even for the most replicated findings there are inconsistent results, not only between studies, but also between the immune effects of the genetic variants and the resulting effects on depression. We find evidence that these discrepant findings may be explained, at least in part, by the heterogeneity of the depression immunophenotype, by environmental influences and gene × environment interactions, and by the complex interfacing of genetic variants with gene expression. Indeed, some of the most robust findings have been obtained in patients developing depression in the context of treatment with interferon-alpha, a widely used model to mimic depression in the context of inflammation. Further 'omics' approaches, through GWAS and transcriptomics, will finally shed light on the interaction between immune genes, their expression, and the influence of the environment, in the pathogenesis of depression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/npp.2016.169

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Clinical studies report higher levels of circulating pro-inflammatory cytokines in MDD patients, a pattern replicated in preclinical animal models of depression.

    “clinical studies report higher levels of circulating pro-inflammatory cytokines in MDD patients, a pattern that has been replicated in preclinical animal models of depression1, 7–10.”

    From Social stress induces neurovascular pathology promoting depression (2017) · cites this paper as [8]

    The Introduction (page not provided) reports increased inflammatory cytokines in the peripheral blood of some patients with major depression, supporting the clinical portion. The Materials and methods section (page not provided) says papers concerning animal models were excluded, so this source does not support the claimed replication in preclinical animal models. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder.

    “Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder.”

    From Social stress induces neurovascular pathology promoting depression (2017) · cites this paper as [8]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 141 · Cited by 237

Research works printed but not linked: 124

  1. Almeida OP, Norman PE, Allcock R, van Bockxmeer F, Hankey GJ, Jamrozik K et al (2009). Polymorphisms of the CRP gene inhibit inflammatory response and increase susceptibility to depression: the Health in Men Study. Int J Epidemiol 38: 1049–1059. 19433520 PMC2720397
  2. Altamura AC, Mundo E, Cattaneo E, Pozzoli S, Dell'osso B, Gennarelli M et al (2010). The MCP-1 gene (SCYA2) and mood disorders: preliminary results of a case-control association study. Neuroimmunomodulation 17: 126–131. 19923858
  3. Ancelin M, Farré A, Carrière I, Ritchie K, Chaudieu I, Ryan J (2015). C-reactive protein gene variants: independent association with late-life depression and circulating protein levels. Translat Psychiatry 5: e499. PMC4312833 25603415
  4. Baumeister D, Akhtar R, Ciufolini S, Pariante C, Mondelli V (2015). Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry 21: 642–649. 26033244 PMC4564950
  5. Baune BT, Dannlowski U, Domschke K, Janssen DG, Jordan MA, Ohrmann P et al (2010). The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression. Biol Psychiatry 67: 543–549. 20044070
  6. Belzeaux R, Bergon A, Jeanjean V, Loriod B, Formisano-Tréziny C, Verrier L et al (2012). Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode. Translat Psychiatry 2: e185. PMC3565773 23149449
  7. Belzeaux R, Azorin J, Ibrahim E (2014). Monitoring candidate gene expression variations before, during and after a first major depressive episode in a 51-year-old man. BMC Psychiatry 14: 73. 24620999 PMC3995670
  8. Borkowska P, Kucia K, Rzezniczek S, Paul-Samojedny M, Kowalczyk M, Owczarek A et al (2011). Interleukin-1beta promoter (31T/C and 511C/T) polymorphisms in major recurrent depression. J Mol Neurosci 44: 12–16. 21465264 PMC3076565
  9. Bosker FJ, Hartman CA, Nolte IM, Prins BP, Terpstra P, Posthuma D et al (2010). Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry 16: 516–532. 20351714
  10. Bosker FJ, Hartman CA, Nolte IM, Prins BP, Terpstra P, Posthuma D et al (2011). Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry 16: 516–532. 20351714
  11. Bufalino C, Hepgul N, Aguglia E, Pariante C (2013). The role of immune genes in the association between depression and inflammation: a review of recent clinical studies. Brain Behav Immun 31: 31–47. 22580182
  12. Carvalho L, Bergink V, Sumaski L, Wijkhuijs J, Hoogendijk W, Birkenhager T et al (2014). Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder. Translat Psychiatry 4: e344. PMC3905228 24424390
  13. Carvalho LA, Torre JP, Papadopoulos AS, Poon L, Juruena MF, Markopoulou K et al (2013). Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J Affect Disord 148: 136–140. 23200297
  14. Cattaneo A, Ferrari C, Uher R, Bocchio-Chiavetto L, Riva M, Pariante C (2016). Absolute measurements of macrophage migration inhibitory factor and interleukin-1-beta mRNA levels accurately predict treatment response in depressed patients. Int J Neuropsychopharmacol (e-pub ahead of print). PMC5091822 27207917
  15. Cattaneo A, Gennarelli M, Uher R, Breen G, Farmer A, Aitchison K et al (2013). Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline ‘predictors' and longitudinal ‘targets'. Neuropsychopharmacology 38: 376–376. PMC3547188 22990943
  16. Cerri AP, Arosio B, Viazzoli C, Confalonieri R, Teruzzi F, Annoni G (2009) 308(G/A) TNF-alpha gene polymorphism and risk of depression late in the life. Arch Gerontol Geriatr 49(Suppl. 1): 29–34. 19836613
  17. Cheah S, Lawford B, Young R, Morris C, Voisey J (2015). Association of NOS1AP variants and depression phenotypes in schizophrenia. J Affect Disord 188: 263–269. 26384012
  18. Chen P, Huang K, Zhou G, Zeng Z, Wang T, Li B et al (2011). Common SNPs in CSF2RB are associated with major depression and schizophrenia in the Chinese Han population. World J. Biol. Psychiatry 12: 233–238. 21247258
  19. Chi MH, Lee SY, Chang HH, Yang YK, Lin E, Chen PS (2011). Comparison of antidepressant efficacy-related SNPs among Taiwanese and four populations in the HapMap database. J Formos Med Assoc 110: 478–482. 21742253
  20. Chocano-Bedoya P, Mirzaei F, O'Reilly E, Lucas M, Okereke O, Hu F et al (2014). C-reactive protein, interleukin-6, soluble tumor necrosis factor α receptor 2 and incident clinical depression. J Affect Disord 163: 25–32. 24836084 PMC4029945
  21. Chumaeva N, Hintsanen M, Pulkki-Råback L, Jokela M, Juonala M, Lehtimäki T et al (2014). Interleukin-6 gene polymorphism, chronic stress and atherosclerosis. J Psychosom Res 76: 333–338. 24630186
  22. Cicchetti D, Handley E, Rogosch F (2015). Child maltreatment, inflammation, and internalizing symptoms: Investigating the roles of C-reactive protein, gene variation, and neuroendocrine regulation. Dev Psychopathol 27: 553–566. 25997771 PMC4443869
  23. Clerici M, Arosio B, Mundo E, Cattaneo E, Pozzoli S, Dell'Osso B et al (2009). Cytokine polymorphisms in the pathophysiology of mood disorders. CNS Spectr 14: 419–425. 19890236
  24. Cutler J, Rush A, McMahon F, Laje G (2012). Common genetic variation in the indoleamine-2,3-dioxygenase genes and antidepressant treatment outcome in major depressive disorder. J Psychopharmacol 26: 360–367. 22282879
  25. Doong S, Dhruva A, Dunn L, West C, Paul S, Cooper B et al (2014). Associations Between cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression in patients prior to breast cancer surgery. Biol Res Nurs 17: 237–247. 25304131 PMC5486211
  26. Dunn L, Aouizerat B, Langford D, Cooper B, Dhruva A, Cataldo J et al (2013). Cytokine gene variation is associated with depressive symptom trajectories in oncology patients and family caregivers. Eur J Oncol Nurs 17: 346–353. 23187335 PMC4114773
  27. Elovainio M, Taipale T, Seppälä I, Mononen N, Raitoharju E, Jokela M et al (2015). Activated immune–inflammatory pathways are associated with long-standing depressive symptoms: evidence from gene-set enrichment analyses in the Young Finns Study. J Psychiatr Res 71: 120–125. 26473696
  28. Fertuzinhos SM, Oliveira JR, Nishimura AL, Pontual D, Carvalho DR, Sougey EB et al (2004). Analysis of IL-1alpha, IL-1beta, and IL-1RA [correction of IL-RA] polymorphisms in dysthymia. J Mol Neurosci 22: 251–256. 14997019
  29. Galecki P, Florkowski A, Bienkiewicz M, Szemraj J (2010a). Functional polymorphism of cyclooxygenase-2 gene (G-765C) in depressive patients. Neuropsychobiology 62: 116–120. 20588070
  30. Galecki P, Florkowski A, Bobinska K, Smigielski J, Bienkiewicz M, Szemraj J (2010b). Functional polymorphism of the myeloperoxidase gene (G-463A) in depressive patients. Acta Neuropsychiatrica 22: 218–222. 26952831
  31. Galecki P, Maes M, Florkowski A, Lewinski A, Galecka E, Bienkiewicz M et al (2010c). An inducible nitric oxide synthase polymorphism is associated with the risk of recurrent depressive disorder. Neurosci Lett 486: 184–187. 20869428
  32. Galecki P, Maes M, Florkowski A, Lewinski A, Galecka E, Bienkiewicz M et al (2011). Association between inducible and neuronal nitric oxide synthase polymorphisms and recurrent depressive disorder. J Affect Disord 129: 175–182. 20888049
  33. Gałecki P, Gałecka E, Maes M, Chamielec M, Orzechowska A, Bobińska K et al (2012). The expression of genes encoding for COX-2, MPO, iNOS, and sPLA2-IIA in patients with recurrent depressive disorder. J Affect Disord 138: 360–366. 22331023
  34. Galvao-de Almeida A, Quarantini LC, Sampaio AS, Lyra AC, Parise CL, Parana R et al (2011). Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon- alpha-related depression in hepatitis C. Brain Behav Immun 25: 1491–1497. 21693183
  35. Gaysina D, Pierce M, Richards M, Hotopf M, Kuh D, Hardy R (2010). Association between adolescent emotional problems and metabolic syndrome: the modifying effect of C-reactive protein gene (CRP) polymorphisms. Brain Behav Immun 25: 750–758. PMC3500684 21296145
  36. Guilloux J, Bassi S, Ding Y, Walsh C, Turecki G, Tseng G et al (2014). Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression. Neuropsychopharmacology 40: 701–710. 25176167 PMC4289958
  37. Haastrup E, Bukh JD, Bock C, Vinberg M, Thorner LW, Hansen T et al (2012). Promoter variants in IL18 are associated with onset of depression in patients previously exposed to stressful-life events. J Affect Disord 136: 134–138. 21962565
  38. Halder I, Marsland AL, Cheong J, Muldoon MF, Ferrell RE, Manuck SB (2010). Polymorphisms in the CRP gene moderate an association between depressive symptoms and circulating levels of C-reactive protein. Brain Behav Immun 24: 160–167. 19796676 PMC3074460
  39. Hardy J, Singleton A (2009). Genomewide association studies and human disease. N Engl J Med 360: 1759–1768. 19369657 PMC3422859
  40. Hepgul N, Cattaneo A, Agarwal K, Baraldi S, Borsini A, Bufalino C et al (2016). Transcriptomics in interferon-α-treated patients identifies inflammation-, neuroplasticity- and oxidative stress-related signatures as predictors and correlates of depression. Neuropsychopharmacology 41: 2502–2511. 27067128 PMC4983179
  41. Holtzman S, Abbey SE, Chan C, Bargman JM, Stewart DE (2012). 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 53: 155–161. 22424164
  42. Hong CJ, Yu YW, Chen TJ, Tsai SJ (2005). Interleukin-6 genetic polymorphism and Chinese major depression. Neuropsychobiology 52: 202–205. 16244501
  43. Hori H, Sasayama D, Teraishi T, Yamamoto N, Nakamura S, Ota M et al (2016). Blood-based gene expression signatures of medication-free outpatients with major depressive disorder: integrative genome-wide and candidate gene analyses. Sci Rep 6: 18776. 26728011 PMC4700430
  44. Horowitz MA, Wertz J, Zhu D, Cattaneo A, Musaelyan K, Nikkheslat N et al (2014). Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells. Int J Neuropsychopharmacol 18. PMC4360247 25522414
  45. Huth C, Heid I, Vollmert C, Gieger C, Grallert H, Wolford J et al (2006). IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes 55: 2915–2921. 17003362
  46. Hwang JP, Tsai SJ, Hong CJ, Yang CH, Hsu CD, Liou YJ (2009). Interleukin-1 beta -511C/T genetic polymorphism is associated with age of onset of geriatric depression. Neuromolecular Med 11: 322–327. 19629761
  47. Illi J, Miaskowski C, Cooper B, Levine J, Dunn L, West C et al (2012). Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression. Cytokine 58: 437–447. 22450224 PMC3340525
  48. Jansen R, Penninx B, Madar V, Xia K, Milaneschi Y, Hottenga J et al (2015). Gene expression in major depressive disorder. Mol Psychiatry 21: 339–347. 26008736
  49. Jun TY, Pae CU, Chae JH, Bahk WM, Kim KS, Han H (2002). Report on IL-10 gene polymorphism at position 819 for major depression and schizophrenia in Korean population. Psychiatry Clin Neurosci 56: 177–180. 11952921
  50. Jun TY, Pae CU, Chae JH, Bahk WM, Kim KS, Pyo CW et al (2003a). Tumor necrosis factor-beta gene polymorphism may not be associated with major depressive disorder in the Korean population. Psychiatry Clin Neurosci 57: 31–35. 12519452
  51. Jun TY, Pae CU, Hoon H, Chae JH, Bahk WM, Kim KS et al (2003b). Possible association between G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder in the Korean population. Psychiatr Genet 13: 179–181. 12960751
  52. Kang H, Kim J, Kim S, Shin I, Park S, Kim Y et al (2014). Associations of cytokine genes with Alzheimer's disease and depression in an elderly Korean population. J Neurol Neurosurg Psychiatry 86: 1002–1007. 25315113
  53. Kao C, Jia P, Zhao Z, Kuo P (2012). Enriched pathways for major depressive disorder identified from a genome-wide association study. Int J Neuropsychopharmacol 15: 1401–1411. 22243633
  54. Kim JM, Stewart R, Kim SW, Shin IS, Kim JT, Park MS et al (2011). Associations of cytokine gene polymorphisms with post-stroke depression. World J Biol Psychiatry 13: 579–587. 21793642
  55. Kim J, Stewart R, Kim S, Kang H, Jang J, Kim S et al (2013a). A one year longitudinal study of cytokine genes and depression in breast cancer. J Affect Disord 148: 57–65. 23276701
  56. Kim J, Stewart R, Kim S, Kim S, Bae K, Kang H et al (2013b). Physical health and incident late-life depression: modification by cytokine genes. Neurobiol Aging 1: e1–e9. 22921153
  57. Kitano H, Oda K, Kimura T, Matsuoka Y, Csete M, Doyle J et al (2004). Metabolic syndrome and robustness tradeoffs. Diabetes 53: S6–S15. 15561923
  58. Koido K, Eller T, Kingo K, Koks S, Traks T, Shlik J et al (2009). Interleukin 10 family gene polymorphisms are not associated with major depressive disorder and panic disorder phenotypes. J Psychiatr Res 44: 275–277. 19786281
  59. Kovács D, Eszlari N, Petschner P, Pap D, Vas S, Kovács P et al (2016a). Effects of IL1B single nucleotide polymorphisms on depressive and anxiety symptoms are determined by severity and type of life stress. Brain Behav Immun 56: 96–104 doi: 10.1016/j.bbi.2016.02.012. 26891860 · DOI
  60. Kovács D, Eszlari N, Petschner P, Pap D, Vas S, Kovács P et al (2016b). Interleukin-6 promoter polymorphism interacts with pain and life stress influencing depression phenotypes. J Neural Transm 123: 541–548. 26821321 PMC4846685
  61. Kurrikoff T, Lesch K, Kiive E, Konstabel K, Herterich S, Veidebaum T et al (2012). Association of a functional variant of the nitric oxide synthase 1 gene with personality, anxiety, and depressiveness. Dev Psychopathol 24: 1225–1235. 23062293
  62. Lawford B, Morris C, Swagell C, Hughes I, Young R, Voisey J (2013). NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans. J Affect Disord 147: 87–93. 23146198
  63. Liu Y, Ho R, Mak A (2012). Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord 139: 230–239. 21872339
  64. Lotrich FE, Ferrell RE, Rabinovitz M, Pollock BG (2010). Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha. Clin Neuropharmacol 33: 191–197. 20661026 PMC2911643
  65. Lotrich FE, Loftis JM, Ferrell RE, Rabinovitz M, Hauser P (2011). IL28B polymorphism is associated with both side effects and clearance of hepatitis C during interferon-alpha therapy. J Interferon Cytokine Res 31: 331–336. 21133812 PMC3043990
  66. Luciano M, Houlihan LM, Harris SE, Gow AJ, Hayward C, Starr JM et al (2010). Association of existing and new candidate genes for anxiety, depression and personality traits in older people. Behav Genet 40: 518–532. 20052609
  67. Mamdani F, Berlim M, Beaulieu M, Labbe A, Merette C, Turecki G (2011). Gene expression biomarkers of response to citalopram treatment in major depressive disorder. Translat Psychiatry 1: e13. PMC3309465 22832429
  68. Manuck SB, Flory JD, Ferrell RE, Muldoon MF (2004). Socio-economic status covaries with central nervous system serotonergic responsivity as a function of allelic variation in the serotonin transporter gene-linked polymorphic region. Psychoneuroendocrinology 29: 651–668. 15041087
  69. McCaffery JM, Duan QL, Frasure-Smith N, Barhdadi A, Lesperance F, Theroux P et al (2009). Genetic predictors of depressive symptoms in cardiac patients. Am J Med Genet B Neuropsychiatr Genet 150B: 381–388. 18618671 PMC2660383
  70. McCulley MC, Day IN, Holmes C (2004). Association between interleukin 1-beta promoter (511) polymorphism and depressive symptoms in Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet 124B: 50–53. 14681913
  71. Mehta D, Raison C, Woolwine B, Haroon E, Binder E, Miller A et al (2013). Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression. Brain Behav Immun 31: 205–215. 23624296 PMC3673885
  72. Mendlewicz J, Crisafulli C, Calati R, Kocabas N, Massat I, Linotte S et al (2012). Influence of COX-2 and OXTR polymorphisms on treatment outcome in treatment resistant depression. Neurosci Lett 516: 85–88. 22487732
  73. Michopoulos V, Rothbaum A, Jovanovic T, Almli L, Bradley B, Rothbaum B et al (2015). Association of CRP genetic variation and CRP level with elevated PTSD symptoms and physiological responses in a civilian population with high levels of trauma. Am J Psychiatry 172: 353–362. 25827033 PMC4440454
  74. Minelli A, Magri C, Barbon A, Bonvicini C, Segala M, Congiu C et al (2015). Proteasome system dysregulation and treatment resistance mechanisms in major depressive disorder. Translat Psychiatry 5: e687. PMC5068581 26624926
  75. Misener VL, Gomez L, Wigg KG, King N, Kiss E, Daroczi G et al (2009). Tagging SNP association study of the IL-1beta gene (IL1B) and childhood-onset mood disorders. Am J Med Genet B Neuropsychiatr Genet 150B: 653–659. 19016479
  76. Misener VL, Gomez L, Wigg KG, Luca P, King N, Kiss E et al (2008). Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and childhood-onset mood disorders. Neuropsychobiology 58: 71–80. 18832862
  77. Montesanto A, Crocco P, Tallaro F, Pisani F, Mazzei B, Mari V et al (2013). Common polymorphisms in nitric oxide synthase (NOS) genes influence quality of aging and longevity in humans. Biogerontology 14: 177–186. 23572278
  78. Morag A, Pasmanik-Chor M, Oron-Karni V, Rehavi M, Stingl J, Gurwitz D (2011). Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker. Pharmacogenomics 12: 171–184. 21332311
  79. Mostafavi S, Battle A, Zhu X, Potash J, Weissman M, Shi J et al (2013). Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing. Mol Psychiatry 19: 1267–1274. 24296977 PMC5404932
  80. Okbay A, Baselmans B, De Neve J, Turley P, Nivard M, Fontana M et al (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat Genet 48: 624–633 doi: 10.1038/ng.3552. 27089181 PMC4884152 · DOI · Paper page
  81. Okumura T, Kishi T, Okochi T, Ikeda M, Kitajima T, Yamanouchi Y et al (2010). Genetic association analysis of functional polymorphisms in neuronal nitric oxide synthase 1 gene (NOS1) and mood disorders and fluvoxamine response in major depressive disorder in the Japanese population. Neuropsychobiology 61: 57–63. 20016223
  82. Oved K, Morag A, Pasmanik-Chor M, Oron-Karni V, Shomron N, Rehavi M et al (2012). Genome-wide miRNA expression profiling of human lymphoblastoid cell lines identifies tentative SSRI antidepressant response biomarkers. Pharmacogenomics 13: 1129–1139. 22909203
  83. Oxenkrug G, Perianayagam M, Mikolich D, Requintina P, Shick L, Ruthazer R et al (2011). Interferon-gamma (+874) T/A genotypes and risk of IFN-alpha-induced depression. J Neural Trans 118: 271–274. PMC3079262 21161299
  84. Pae CU, Yu HS, Kim JJ, Lee CU, Lee SJ, Lee KU et al (2004a). BanI polymorphism of the cytosolic phospholipase A2 gene and mood disorders in the Korean population. Neuropsychobiology 49: 185–188. 15118355
  85. Pae CU, Yu HS, Kim TS, Lee CU, Lee SJ, Jun TY et al (2004b). Monocyte chemoattractant protein-1 (MCP1) promoter -2518 polymorphism may confer a susceptibility to major depressive disorder in the Korean population. Psychiatry Res 127: 279–281. 15296827
  86. Pariante C, Nemeroff C (2012). Unipolar depression. Neurobiol Psychiatric Disord 239–249. 22608625
  87. Pawlowski T, Radkowski M, Małyszczak K, Inglot M, Zalewska M, Jablonska J et al (2014). Depression and neuroticism in patients with chronic hepatitis C: correlation with peripheral blood mononuclear cells activation. J Clin Virol 60: 105–111. 24742598
  88. Peters A (2006). The energy request of inflammation. Endocrinology 147: 4550–4552. 16980440
  89. Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J (1992). A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 22: 396–402. 1353022
  90. Pollak Y, Yirmiya R (2002). Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition', immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol 5: 389–399. 12466037
  91. Powell T, Schalkwyk L, Heffernan A, Breen G, Lawrence T, Price T et al (2013a). Tumor necrosis factor and its targets in the inflammatory cytokine pathway are identified as putative transcriptomic biomarkers for escitalopram response. Eur Neuropsychopharmacol 23: 1105–1114. 23142150
  92. Powell T, Tansey K, Breen G, Farmer A, Craig I, Uher R et al (2013b). ATP-binding cassette sub-family F member 1 (ABCF1) is identified as a putative therapeutic target of escitalopram in the inflammatory cytokine pathway. J Psychopharmacol 27: 609–615. 23719290
  93. Raison C, Rutherford R, Woolwine B, Shuo C, Schettler P, Drake D et al (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression. JAMA Psychiatry 70: 31–41. 22945416 PMC4015348
  94. Rana B, Darst B, Bloss C, Shih P, Depp C, Nievergelt C et al (2014). Candidate SNP associations of optimism and resilience in older adults: exploratory study of 935 community-dwelling adults. Am J Geriatr Psychiatry 22: 997–1006.e5. 24791650 PMC4163500
  95. Reyes-Gibby C, Wang J, Spitz M, Wu X, Yennurajalingam S, Shete S (2013a). Genetic variations in interleukin-8 and interleukin-10 are associated with pain, depressed mood, and fatigue in lung cancer patients. J Pain Symptom Manage 46: 161–172. 23149083 PMC3578112
  96. Reyes-Gibby C, Swartz M, Yu X, Wu X, Yennurajalingam S, Anderson K et al (2013b). Symptom clusters of pain, depressed mood, and fatigue in lung cancer: assessing the role of cytokine genes. Support Care Cancer 21: 3117–3125. 23852407 PMC3923575
  97. Ridout K, Parade S, Seifer R, Price L, Gelernter J, Feliz P et al (2014). Interleukin 1B gene (IL1B) variation and internalizing symptoms in maltreated preschoolers. Dev Psychopathol 26: 1277–1287. 25422961 PMC4459595
  98. Ripke S, Wray N, Lewis C, Hamilton S, Weissman M, Breen G et al (2012). A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry 18: 497–511. 22472876 PMC3837431
  99. Roetker N, Yonker J, Lee C, Chang V, Basson J, Roan C et al (2012). Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study. BMJ Open 2. PMC3391375 22761283
  100. Rosa A, Peralta V, Papiol S, Cuesta MJ, Serrano F, Martinez-Larrea A et al (2004). Interleukin-1beta (IL-1beta) gene and increased risk for the depressive symptom-dimension in schizophrenia spectrum disorders. Am J Med Genet B Neuropsychiatr Genet 124B: 10–14. 14681906
  101. Rovin BH, Lu L, Saxena R (1999). A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 259: 344–348. 10362511
  102. Saad S, Dunn L, Koetters T, Dhruva A, Langford D, Merriman J et al (2014). Cytokine gene variations associated with subsyndromal depressive symptoms in patients with breast cancer. Eur J Oncol Nurs 18: 397–404. 24726621 PMC4074554
  103. Sarginson J, Deakin J, Anderson I, Downey D, Thomas E, Elliott R et al (2014). Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk. Neuropsychopharmacology 39: 2857–2866. 24917196 PMC4200496
  104. Savitz J, Frank M, Victor T, Bebak M, Marino J, Bellgowan P et al (2013). Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities. Brain Behav Immun 31: 161–171. 23064081 PMC3577998
  105. Song G, Kim J, Lee Y (2013). Genome-wide pathway analysis in major depressive disorder. J Mol Neurosci 51: 428–436. 23794217
  106. Spijker S, Van Zanten J, De Jong S, Penninx B, van Dyck R, Zitman F et al (2010). Stimulated gene expression profiles as a blood marker of major depressive disorder. Biol Psychiatry 68: 179–186. 20471630
  107. Su KP, Huang SY, Peng CY, Lai HC, Huang CL, Chen YC et al (2010). Phospholipase A2 and cyclooxygenase 2 genes influence the risk of interferon-alpha-induced depression by regulating polyunsaturated fatty acids levels. Biol Psychiatry 67: 550–557. 20034614 PMC2982743
  108. Su K, Lai H, Yang H, Su W, Peng C, Chang J et al (2014). Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial. Biol Psychiatry 76: 559–566. 24602409
  109. Su S, Miller AH, Snieder H, Bremner JD, Ritchie J, Maisano C et al (2009). Common genetic contributions to depressive symptoms and inflammatory markers in middle-aged men: the twins heart study. Psychosom Med 71: 152–158. 19073752 PMC2904952
  110. Sullivan P, Neale M, Kendler K (2000). Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 157: 1552–1562. 11007705
  111. Tadic A, Rujescu D, Muller MJ, Kohnen R, Stassen HH, Szegedi A et al (2008). Association analysis between variants of the interleukin-1beta and the interleukin-1 receptor antagonist gene and antidepressant treatment response in major depression. Neuropsychiatr Dis Treat 4: 269–276. 18728809 PMC2515903
  112. Tarabay M, Elshazli R, Settin A (2016). African vs. Caucasian and Asian difference for the association of interleukin-10 promotor polymorphisms with type 2 diabetes mellitus (a meta-analysis study). Meta Gene 9: 10–17. 27114918 PMC4833051
  113. Tartter M, Hammen C, Bower J, Brennan P, Cole S (2015). Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and IL1β in youth. Brain Behav Immun 46: 104–111. 25596176 PMC4515110
  114. Torres K, Araújo Pereira P, Lima G, Bozzi I, Rezende V, Bicalho M et al (2013). Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in late-onset depression patients. Prog Neuropsychopharmacol Biol Psychiatry 47: 40–45. 23954740
  115. Traks T, Koido K, Eller T, Maron E, Kingo K, Vasar V et al (2008). Polymorphisms in the interleukin-10 gene cluster are possibly involved in the increased risk for major depressive disorder. BMC Med Genet 9: 111. 19087313 PMC2648955
  116. Udina M, Moreno-España J, Navinés R, Giménez D, Langohr K, Gratacòs M et al (2013). Serotonin and interleukin-6: the role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms. Psychoneuroendocrinology 38: 1803–1813. 23571152
  117. Uher R, Perroud N, Ng M, Hauser J, Henigsberg N, Maier W et al (2010). Genome-wide pharmacogenetics of antidepressant response in the GENDEP Project. Am J Psychiatry 167: 555–564. 20360315
  118. Wium-Andersen M, Ørsted D, Nordestgaard B (2014). Elevated C-reactive protein, depression, somatic diseases, and all-cause mortality: a Mendelian Randomization Study. Biol Psychiatry 76: 249–257. 24246360
  119. Yoshida K, Alagbe O, Wang X, Woolwine B, Thornbury M, Raison CL et al (2005). Promoter polymorphisms of the interferon-alpha receptor gene and development of Interferon-induced depressive symptoms in patients with chronic hepatitis C: preliminary findings. Neuropsychobiology 52: 55–61. 15990456
  120. Yu YW, Chen TJ, Hong CJ, Chen HM, Tsai SJ (2003a). Association study of the interleukin-1 beta (C-511T) genetic polymorphism with major depressive disorder, associated symptomatology, and antidepressant response. Neuropsychopharmacology 28: 1182–1185. 12700687
  121. Yu YW, Chen TJ, Wang YC, Liou YJ, Hong CJ, Tsai SJ (2003b). Association analysis for neuronal nitric oxide synthase gene polymorphism with major depression and fluoxetine response. Neuropsychobiology 47: 137–140. 12759556
  122. Zhang Y, Zhang J, Tian C, Narenqimuge, Deng Y, Zhao Y et al (2011). The −2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and diabetes risk: a meta-analysis. Diabetes Res Clin Pract 94: e89–e92. 21992868
  123. Zhao J, Quyyumi AA, Patel R, Zafari AM, Veledar E, Onufrak S et al (2009). Sex-specific association of depression and a haplotype in leukotriene A4 hydrolase gene. Psychosom Med 71: 691–696. 19622707 PMC3113512
  124. Zhao Y, Li Z, Zhang L, Zhang Y, Yang Y, Tang Y et al (2013). The TNF-alpha -308G/A polymorphism is associated with type 2 diabetes mellitus: an updated meta-analysis. Mol Biol Rep 41: 73–83. 24197696

Authors
Barnes, J., Mondelli, V., & Pariante, C. M.
Affiliations
King's College London (GB)
Corresponding author
Pariante, Carmine M
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2016-08-24
Volume
42
Issue
1
Pages
81-98
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2016.169
PMC
PMC5143493
OpenAlex
W2512238452
Cited by
237
References
141
Citations by year
2026: 14 · 2025: 26 · 2024: 23 · 2023: 27 · 2022: 27 · 2021: 34 · 2020: 26 · 2019: 20 · 2018: 18 · 2017: 17 · 2016: 4
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, other-oa)
Funders
  • South London and Maudsley NHS Foundation Trust
  • Wellcome Trust
  • National Institute for Health and Care Research (CL-2008-17-005, NF-SI-0616-10074)
  • Academy of Medical Sciences (AMS-SGCL5-Mondelli)
  • H. Lundbeck A/S
  • Medical Research Council (MR/N029488/1, MR/J002739/1, MR/L014815/1)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
depression, inflammation, immune-related genes, genetic polymorphism, cytokine gene expression, antidepressant response, IL-1β, interleukin-6, IL-10, TNF-α, C-reactive protein, phospholipase A2, gene-environment interaction, depression pathogenesis
MeSH terms
Depressive Disorder, Humans, Inflammation, Cytokines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review