Skip to main content

Abnormal levels of vascular endothelial biomarkers in schizophrenia

European Archives of Psychiatry and Clinical Neuroscience volume 268, pages 849–860 (2018)Cite this article

Abstract

Schizophrenia is associated with chronic low-grade inflammation, which has been linked to increased vascular risk and rates of cardiovascular disease. Levels of vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) have been related to aging and neurodegeneration, but their role in schizophrenia remains uncertain. Using a cross-sectional, case–control design, this study included 99 outpatients with schizophrenia and 99 healthy comparison subjects (HCs). Sociodemographic and clinical data were collected, and plasma levels of VEGF, ICAM-1, and VCAM-1 were assayed. A “vascular endothelial index” (VEI) was computed using logistic regression to create a composite measure that maximally differed between groups. General linear models were conducted to examine the possible role of demographic, physical, and lifestyle factors. A linear combination of ICAM-1 and VCAM-1 levels best distinguished the groups, with significantly higher levels of this composite VEI in persons with schizophrenia than HCs. Group differences in the VEI persisted after adjustment for BMI and cigarette smoking. Neither age nor gender was significantly related to the VEI. Schizophrenia patients with higher VEI had earlier age of disease onset, higher systolic and diastolic blood pressure, lower high-density lipoprotein cholesterol, higher insulin resistance, lower levels of mental well-being, and higher Framingham Coronary Heart Disease Risk scores. Schizophrenia is characterized by an elevation of vascular endothelial biomarkers, specifically cell adhesion molecules poised at the intersection between inflammatory response and vascular risk. Interventions aimed at reducing vascular risk may help reduce vascular endothelial abnormalities and prevent cardiovascular morbidity and mortality in schizophrenia.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Osby U, Westman J, Hallgren J, Gissler M (2016) Mortality trends in cardiovascular causes in schizophrenia, bipolar and unipolar mood disorder in Sweden 1987–2010. Eur J Pub Health 26(5):867–871. doi:10.1093/eurpub/ckv245

    Article  Google Scholar 

  2. Fan Z, Wu Y, Shen J, Ji T, Zhan R (2013) Schizophrenia and the risk of cardiovascular diseases: a meta-analysis of thirteen cohort studies. J Psychiatr Res 47(11):1549–1556. doi:10.1016/j.jpsychires.2013.07.011

    Article  PubMed  Google Scholar 

  3. Grande I, Magalhães PV, Kunz M, Vieta E, Kapczinski F (2012) Mediators of allostasis and systemic toxicity in bipolar disorder. Physiol Behav 106(1):46–50. doi:10.1016/j.physbeh.2011.10.029

    CAS  Article  PubMed  Google Scholar 

  4. Tomasik J, Rahmoune H, Guest PC, Bahn S (2016) Neuroimmune biomarkers in schizophrenia. Schizophr Res 176(1):3–13. doi:10.1016/j.schres.2014.07.025

    Article  PubMed  Google Scholar 

  5. Mahendran R, Mahendran R, Chan YH (2004) Interleukin-2 levels in chronic schizophrenia patients. Ann Acad Med Singapore 33(3):320–323

    CAS  PubMed  Google Scholar 

  6. Lee EE, Hong S, Martin AS, Eyler LT, Jeste DV (2016) Inflammation in schizophrenia: cytokine levels and their relationships to demographic and clinical variables. Am J Geriatr Psychiatry 25(1):50–61

    Article  Google Scholar 

  7. Joseph J, Depp C, Martin AS, Daly RE, Glorioso DK, Palmer BW, Jeste DV (2015) Associations of high sensitivity C-reactive protein levels in schizophrenia and comparison groups. Schizophr Res 168(1–2):456–460. doi:10.1016/j.schres.2015.08.019

    Article  PubMed  PubMed Central  Google Scholar 

  8. Khansari N, Shakiba Y, Mahmoudi M (2009) Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov 3(1):73–80

    CAS  Article  Google Scholar 

  9. Willerson JT, Ridker PM (2004) Inflammation as a cardiovascular risk factor. Circulation 109(21 Suppl 1):II2–II10. doi:10.1161/01.CIR.0000129535.04194.38

    Article  PubMed  Google Scholar 

  10. Libby P, Ridker PM, Hansson GK (2011) Progress and challenges in translating the biology of atherosclerosis. Nature 473(7347):317–325. doi:10.1038/nature10146

    CAS  Article  PubMed  Google Scholar 

  11. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444(7121):860–867. doi:10.1038/nature05485

    CAS  Article  Google Scholar 

  12. Zhou Y, Han W, Gong D, Man C, Fan Y (2016) Hs-CRP in stroke: a meta-analysis. Clin Chim Acta 453:21–27. doi:10.1016/j.cca.2015.11.027

    CAS  Article  PubMed  Google Scholar 

  13. Legein B, Temmerman L, Biessen EA, Lutgens E (2013) Inflammation and immune system interactions in atherosclerosis. Cell Mol Life Sci 70(20):3847–3869. doi:10.1007/s00018-013-1289-1

    CAS  Article  PubMed  Google Scholar 

  14. Hall JR, Wiechmann AR, Johnson LA, Edwards M, Barber RC, Winter AS, Singh M, O’Bryant SE (2013) Biomarkers of vascular risk, systemic inflammation, and microvascular pathology and neuropsychiatric symptoms in Alzheimer’s disease. J Alzheimer’s Dis 35(2):363–371. doi:10.3233/JAD-122359

    CAS  Article  Google Scholar 

  15. Liao JK (2013) Linking endothelial dysfunction with endothelial cell activation. J Clin Investig 123(2):540–541. doi:10.1172/JCI66843

    CAS  Article  PubMed  Google Scholar 

  16. Davies MJ, Gordon JL, Gearing AJ, Pigott R, Woolf N, Katz D, Kyriakopoulos A (1993) The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J Pathol 171(3):223–229. doi:10.1002/path.1711710311

    CAS  Article  PubMed  Google Scholar 

  17. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56(4):549–580. doi:10.1124/pr.56.4.3

    CAS  Article  PubMed  Google Scholar 

  18. Kakizawa H, Itoh M, Itoh Y, Imamura S, Ishiwata Y, Matsumoto T, Yamamoto K, Kato T, Ono Y, Nagata M (2004) The relationship between glycemic control and plasma vascular endothelial growth factor and endothelin-1 concentration in diabetic patients. Metabolism 53(5):550–555

    CAS  Article  Google Scholar 

  19. Shoamanesh A, Preis SR, Beiser AS, Kase CS, Wolf PA, Vasan RS, Benjamin EJ, Seshadri S, Romero JR (2016) Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study. Neurology. doi:10.1212/wnl.0000000000003115

    Article  PubMed  PubMed Central  Google Scholar 

  20. Harmey JH (2004) VEGF and cancer. Springer, Berlim

    Book  Google Scholar 

  21. Brandes RP, Fleming I, Busse R (2005) Endothelial aging. Cardiovasc Res 66(2):286–294. doi:10.1016/j.cardiores.2004.12.027

    CAS  Article  PubMed  Google Scholar 

  22. Seals DR, Jablonski KL, Donato AJ (2011) Aging and vascular endothelial function in humans. Clin Sci 120(9):357–375. doi:10.1042/CS20100476

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Richter V, Rassoul F, Purschwitz K, Hentschel B, Reuter W, Kuntze T (2003) Circulating vascular cell adhesion molecules VCAM-1, ICAM-1, and E-selectin in dependence on aging. Gerontology 49(5):293–300. doi:10.1159/000071710

    CAS  Article  PubMed  Google Scholar 

  24. Miguel-Hidalgo JJ, Nithuairisg S, Stockmeier C, Rajkowska G (2007) Distribution of ICAM-1 immunoreactivity during aging in the human orbitofrontal cortex. Brain Behav Immun 21(1):100–111

    CAS  Article  Google Scholar 

  25. Morisaki N, Saito I, Tamura K, Tashiro J, Masuda M, Kanzaki T, Watanabe S, Masuda Y, Saito Y (1997) New indices of ischemic heart disease and aging: studies on the serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic heart disease. Atherosclerosis 131(1):43–48. doi:10.1016/S0021-9150(97)06083-8

    CAS  Article  PubMed  Google Scholar 

  26. Ewers M, Mielke MM, Hampel H (2010) Blood-based biomarkers of microvascular pathology in Alzheimer’s disease. Exp Gerontol 45(1):75–79. doi:10.1016/j.exger.2009.09.005

    CAS  Article  PubMed  Google Scholar 

  27. Kirkpatrick B, Messias E, Harvey PD, Fernandez-Egea E, Bowie CR (2008) Is schizophrenia a syndrome of accelerated aging? Schizophr Bull 34(6):1024–1032. doi:10.1093/schbul/sbm140

    Article  PubMed  Google Scholar 

  28. Demerath E, Towne B, Blangero J, Siervogel RM (2001) The relationship of soluble ICAM-1, VCAM-1, P-selectin and E-selectin to cardiovascular disease risk factors in healthy men and women. Ann Hum Biol 28(6):664–678

    CAS  Article  Google Scholar 

  29. Chen Y, Osika W, Dangardt F, Gan LM, Strandvik B, Friberg P (2010) High levels of soluble intercellular adhesion molecule-1, insulin resistance and saturated fatty acids are associated with endothelial dysfunction in healthy adolescents. Atherosclerosis 211(2):638–642. doi:10.1016/j.atherosclerosis.2010.03.013

    CAS  Article  PubMed  Google Scholar 

  30. Pillai A, Howell KR, Ahmed AO, Weinberg D, Allen KM, Bruggemann J, Lenroot R, Liu D, Galletly C, Weickert CS, Weickert TW (2016) Association of serum VEGF levels with prefrontal cortex volume in schizophrenia. Mol Psychiatry 21(5):686–692. doi:10.1038/mp.2015.96

    CAS  Article  PubMed  Google Scholar 

  31. Schwarz MJ, Riedel M, Ackenheil M, Müller N (1999) Levels of soluble adhesion molecules in schizophrenia: relation to psychopathology. In: Müller N (ed) Psychiatry, psychoimmunology, and viruses. Springer Vienna, Vienna, pp 121–130. doi:10.1007/978-3-7091-6404-4_13

    Chapter  Google Scholar 

  32. Schwarz MJ, Riedel M, Ackenheil M, Müller N (2000) Decreased levels of soluble intercellular adhesion molecule-1 (sICAM-1) in unmedicated and medicated schizophrenic patients. Biol Psychiatry 47(1):29–33. doi:10.1016/S0006-3223(99)00206-1

    CAS  Article  PubMed  Google Scholar 

  33. Beumer W, Drexhage RC, De Wit H, Versnel MA, Drexhage HA, Cohen D (2012) Increased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome. Psychoneuroendocrinology 37(12):1901–1911. doi:10.1016/j.psyneuen.2012.04.001

    CAS  Article  PubMed  Google Scholar 

  34. Stefanović MP, Petronijević N, Dunjić-Kostić B, Velimirović M, Nikolić T, Jurišić V, Lačković M, Damjanović A, Totić-Poznanović S, Jovanović AA, Ivković M (2016) Role of sICAM-1 and sVCAM-1 as biomarkers in early and late stages of schizophrenia. J Psychiatr Res 73:45–52. doi:10.1016/j.jpsychires.2015.11.002

    Article  PubMed  Google Scholar 

  35. Al Suwaidi J, Higano ST, Holmes DR Jr, Lennon R, Lerman A (2001) Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries. J Am Coll Cardiol 37(6):1523–1528

    CAS  Article  Google Scholar 

  36. Schumacher A, Seljeflot I, Sommervoll L, Christensen B, Otterstad J, Arnesen H (2002) Increased levels of markers of vascular inflammation in patients with coronary heart disease. Scand J Clin Lab Invest 62(1):59–68

    CAS  Article  Google Scholar 

  37. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD (1996) Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Investig 97(11):2601–2610

    CAS  Article  Google Scholar 

  38. Coodin S (2001) Body mass index in persons with schizophrenia. Can j Psychiatry Revue 46(6):549–555

    CAS  Article  Google Scholar 

  39. de Leon J (1996) Smoking and vulnerability for schizophrenia. Schizophr Bull 22(3):405–409

    Article  Google Scholar 

  40. First M, Spitzer RL, Gibbon M, Williams JB (2002) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition With Psychotic Screen (SCID-I/PW/PSY SCREEN) New York: Biometrics Research, New York State Psychiatric Institute; 2002; Biometrics Research. New York State Psychiatric Institute, New York

    Google Scholar 

  41. Amann BL, Canales-Rodriguez EJ, Madre M, Radua J, Monte G, Alonso-Lana S, Landin-Romero R, Moreno-Alcazar A, Bonnin CM, Sarro S, Ortiz-Gil J, Gomar JJ, Moro N, Fernandez-Corcuera P, Goikolea JM, Blanch J, Salvador R, Vieta E, McKenna PJ, Pomarol-Clotet E (2016) Brain structural changes in schizoaffective disorder compared to schizophrenia and bipolar disorder. Acta Psychiatr Scand 133(1):23–33. doi:10.1111/acps.12440

    CAS  Article  PubMed  Google Scholar 

  42. Evans JD, Heaton RK, Paulsen JS, McAdams LA, Heaton SC, Jeste DV (1999) Schizoaffective disorder: a form of schizophrenia or affective disorder? J Clin Psychiatry 60(12):874–882

    CAS  Article  Google Scholar 

  43. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33

    PubMed  PubMed Central  Google Scholar 

  44. Hong S, Lee EE, Martin AS, Soontornniyomkij B, Soontornniyomkij V, Achim CL, Reuter C, Irwin MR, Eyler LT, Jeste DV (2016) Abnormalities in chemokine levels in schizophrenia and their clinical correlates. Schizophr Res. doi:10.1016/j.schres.2016.09.019

    Article  PubMed  PubMed Central  Google Scholar 

  45. Lee EE, Eyler LT, Wolkowitz OM, Martin AS, Reuter C, Kraemer H, Jeste DV (2016) Elevated plasma F2-isoprostane levels in schizophrenia. Schizophr Res. doi:10.1016/j.schres.2016.06.011

    Article  PubMed  PubMed Central  Google Scholar 

  46. WHO Collaborating Centre for Drug Statistics Methodology (2009) Guidelines for ATC classification and DDD assignment 2010

  47. Andreasen NC (1983) Scale for the assessment of negative symptoms (SANS). University of Iowa, Iowa City

    Google Scholar 

  48. Andreasen NC (1984) Scale for the assessment of positive symptoms (SAPS). University of Iowa, Iowa City

    Google Scholar 

  49. Kroenke K, Spitzer RL (2002) The PHQ-9: a new depression diagnostic and severity measure. Psychiatr Ann 32(9):509–515

    Article  Google Scholar 

  50. Ware Jr JE, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Medical care 30(6):473–483

    Article  Google Scholar 

  51. Parmelee PA, Thuras PD, Katz IR, Lawton MP (1995) Validation of the cumulative illness rating scale in a geriatric residential population. J Am Geriatr Soc 43(2):130–137

    CAS  Article  Google Scholar 

  52. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97(18):1837–1847

    CAS  Article  Google Scholar 

  53. D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, Kannel WB (2008) General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 117(6):743–753. doi:10.1161/CIRCULATIONAHA.107.699579

    Article  PubMed  Google Scholar 

  54. Frydecka D, Misiak B, Pawlak-Adamska E, Karabon L, Tomkiewicz A, Sedlaczek P, Kiejna A, Beszlej JA (2015) Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation. Eur Arch Psychiatry Clin Neurosci 265(6):449–459. doi:10.1007/s00406-014-0533-5

    Article  PubMed  Google Scholar 

  55. Bulzacka E, Boyer L, Schurhoff F, Godin O, Berna F, Brunel L, Andrianarisoa M, Aouizerate B, Capdevielle D, Chereau-Boudet I, Chesnoy-Servanin G, Danion JM, Dubertret C, Dubreucq J, Faget C, Gabayet F, Le Gloahec T, Llorca PM, Mallet J, Misdrahi D, Rey R, Richieri R, Passerieux C, Roux P, Yazbek H, Leboyer M, Fond G (2016) Chronic peripheral inflammation is associated with cognitive impairment in schizophrenia: results from the multicentric FACE-SZ dataset. Schizophr Bull 42(5):1290–1302. doi:10.1093/schbul/sbw029

    Article  PubMed  PubMed Central  Google Scholar 

  56. Delis DC, Kaplan E, Kramer JH (2001) The Delis–Kaplan executive function system: examiner’s manual. Psychol Corp, San Antonio

    Google Scholar 

  57. Gibbons LE, Carle AC, Mackin RS, Harvey D, Mukherjee S, Insel P, Curtis SM, Mungas D, Crane PK, Alzheimer’s Disease Neuroimaging I (2012) A composite score for executive functioning, validated in Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants with baseline mild cognitive impairment. Brain Imaging Behav 6(4):517–527. doi:10.1007/s11682-012-9176-1

    Article  PubMed  PubMed Central  Google Scholar 

  58. Calvier L, Legchenko E, Grimm L, Sallmon H, Hatch A, Plouffe BD, Schroeder C, Bauersachs J, Murthy SK, Hansmann G (2016) Galectin-3 and aldosterone as potential tandem biomarkers in pulmonary arterial hypertension. Heart 102(5):390–396. doi:10.1136/heartjnl-2015-308365

    CAS  Article  PubMed  Google Scholar 

  59. IBM Corporation (2011) IBM SPSS Statistics for Macintosh, Version 20.0. IBM Corporation, Armonk, NY

  60. Core Team R (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  61. Thomas AJ, Davis S, Ferrier IN, Kalaria RN, O’Brien JT (2004) Elevation of cell adhesion molecule immunoreactivity in the anterior cingulate cortex in bipolar disorder. Biol Psychiatry 55(6):652–655. doi:10.1016/j.biopsych.2003.10.015

    CAS  Article  PubMed  Google Scholar 

  62. Kavzoglu SO, Hariri AG (2013) Intracellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and E-selectin levels in first episode schizophrenic patients. Bull Clin Psychopharmacol 23(3):204–214

    Article  Google Scholar 

  63. Arolt V, Rothermundt M, Wandinger KP, Kirchner H (2000) Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry 5(2):150–158

    CAS  Article  Google Scholar 

  64. Muller N, Ackenheil M, Hofschuster E, Mempel W, Eckstein R (1991) Cellular immunity in schizophrenic patients before and during neuroleptic treatment. Psychiatry Res 37(2):147–160

    CAS  Article  Google Scholar 

  65. Steiner J, Jacobs R, Panteli B, Brauner M, Schiltz K, Bahn S, Herberth M, Westphal S, Gos T, Walter M, Bernstein HG, Myint AM, Bogerts B (2010) Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity. Eur Arch Psychiatry Clin Neurosci 260(7):509–518. doi:10.1007/s00406-010-0098-x

    Article  PubMed  Google Scholar 

  66. Na KS, Jung HY, Kim YK (2014) The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 48:277–286. doi:10.1016/j.pnpbp.2012.10.022

    CAS  Article  PubMed  Google Scholar 

  67. Monji A, Kato TA, Mizoguchi Y, Horikawa H, Seki Y, Kasai M, Yamauchi Y, Yamada S, Kanba S (2013) Neuroinflammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry 42:115–121. doi:10.1016/j.pnpbp.2011.12.002

    CAS  Article  PubMed  Google Scholar 

  68. Lee BH, Hong JP, Hwang JA, Ham BJ, Na KS, Kim WJ, Trigo J, Kim YK (2015) Alterations in plasma vascular endothelial growth factor levels in patients with schizophrenia before and after treatment. Psychiatry Res 228(1):95–99. doi:10.1016/j.psychres.2015.04.020

    CAS  Article  PubMed  Google Scholar 

  69. Muller V, Szabo A, Viklicky O, Gaul I, Portl S, Philipp T, Heemann UW (1999) Sex hormones and gender-related differences: their influence on chronic renal allograft rejection. Kidney Int 55(5):2011–2020. doi:10.1046/j.1523-1755.1999.00441.x

    CAS  Article  PubMed  Google Scholar 

  70. Noguchi T (1999) Soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 concentrations, and leukocyte count in smokers. Environ Health Prev Med 4(2):71–74. doi:10.1007/bf02931997

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF, Michel JB (2000) Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol 20(3):645–651

    CAS  Article  Google Scholar 

  72. O’Brien KD, McDonald TO, Chait A, Allen MD, Alpers CE (1996) Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation 93(4):672–682

    Article  Google Scholar 

  73. van der Wal AC, Das PK, Tigges AJ, Becker AE (1992) Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am J Pathol 141(6):1427–1433

    PubMed  PubMed Central  Google Scholar 

  74. Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, Turner RB (2012) Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci USA 109(16):5995–5999. doi:10.1073/pnas.1118355109

    Article  PubMed  Google Scholar 

  75. Okusaga OO (2014) Accelerated aging in schizophrenia patients: the potential role of oxidative stress. Aging Dis 5(4):256–262. doi:10.14336/AD.2014.0500256

    Article  PubMed  Google Scholar 

  76. Madamanchi NR, Vendrov A, Runge MS (2005) Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25(1):29–38. doi:10.1161/01.ATV.0000150649.39934.13

    CAS  Article  PubMed  Google Scholar 

  77. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107(3):499–511

    Article  Google Scholar 

  78. Dimopoulos N, Piperi C, Salonicioti A, Mitropoulos P, Kallai E, Liappas I, Lea RW, Kalofoutis A (2006) Indices of low-grade chronic inflammation correlate with early cognitive deterioration in an elderly Greek population. Neurosci Lett 398(1–2):118–123. doi:10.1016/j.neulet.2005.12.064

    CAS  Article  PubMed  Google Scholar 

  79. Rafnsson SB, Deary IJ, Smith FB, Whiteman MC, Rumley A, Lowe GD, Fowkes FG (2007) Cognitive decline and markers of inflammation and hemostasis: the Edinburgh Artery Study. J Am Geriatr Soc 55(5):700–707. doi:10.1111/j.1532-5415.2007.01158.x

    Article  PubMed  Google Scholar 

  80. Elwan O, Madkour O, Elwan F, Mostafa M, Abbas Helmy A, Abdel-Naseer M, Abdel Shafy S, El Faiuomy N (2003) Brain aging in normal Egyptians: cognition, education, personality, genetic and immunological study. J Neurol Sci 211(1–2):15–22

    Article  Google Scholar 

  81. Iga J, Ueno S, Yamauchi K, Numata S, Tayoshi-Shibuya S, Kinouchi S, Nakataki M, Song H, Hokoishi K, Tanabe H, Sano A, Ohmori T (2007) Gene expression and association analysis of vascular endothelial growth factor in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 31(3):658–663. doi:10.1016/j.pnpbp.2006.12.011

    CAS  Article  PubMed  Google Scholar 

  82. Dimopoulos N, Piperi C, Salonicioti A, Mitsonis C, Liappas I, Lea RW, Kalofoutis A (2006) Elevation of plasma concentration of adhesion molecules in late-life depression. Int J Geriatr Psychiatry 21(10):965–971. doi:10.1002/gps.1592

    Article  PubMed  Google Scholar 

  83. Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M (1997) ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 54(10):915–922

    CAS  Article  Google Scholar 

  84. Taylor WD, Aizenstein HJ, Alexopoulos GS (2013) The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 18(9):963–974. doi:10.1038/mp.2013.20

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O’Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE (2011) Metabolite profiles and the risk of developing diabetes. Nat Med 17(4):448–453. doi:10.1038/nm.2307

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported in part by National Institutes of Health Grant 5R01MH094151-04 (Jeste), UL1 RR031980 for the UCSD Clinical and Translational Research Institute, the VA Desert-Pacific Mental Illness Research Education and Clinical Center and Office of Academic Affiliations (Nguyen, Eyler), and UC San Diego Stein Institute for Research on Aging. We thank Benchawanna Soontornniyomkij, Ph.D., for her help with the assays of the vascular biomarkers, and Rebecca Daly for her major contributions to data management for the project. Parts of these results were presented at the annual conference of the American College of Neuropsychopharmacology in Hollywood, FL, on December 7, 2016.

Author information

Affiliations

  1. VA San Diego Healthcare System, Mental Illness Research, Education, and Clinical Center (MIRECC), San Diego, CA, USA

    Tanya T. Nguyen, Sharon C. Liou & Lisa T. Eyler

  2. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive (MC 0931), La Jolla, San Diego, CA, 92093, USA

    Tanya T. Nguyen, Sheena I. Dev, Averria Sirkin Martin, Dilip V. Jeste & Lisa T. Eyler

  3. San Diego Joint Doctoral Program in Clinical Psychology, San Diego State University, University of California, San Diego, CA, USA

    Sheena I. Dev

  4. Institute for Quantitative Biomedical Sciences, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA

    Guanqing Chen

  5. Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, CA, USA

    Averria Sirkin Martin, Xin Tu, Dilip V. Jeste & Lisa T. Eyler

  6. Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA

    Michael R. Irwin & Judith E. Carroll

  7. Department of Family Medicine and Public Health, University of California, San Diego, CA, USA

    Xin Tu

Authors
  1. Tanya T. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheena I. Dev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guanqing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sharon C. Liou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Averria Sirkin Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael R. Irwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Judith E. Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xin Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dilip V. Jeste
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lisa T. Eyler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lisa T. Eyler.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Dilip V. Jeste and Lisa T. Eyler: Co-senior authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nguyen, T.T., Dev, S.I., Chen, G. et al. Abnormal levels of vascular endothelial biomarkers in schizophrenia. Eur Arch Psychiatry Clin Neurosci 268, 849–860 (2018). https://doi.org/10.1007/s00406-017-0842-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-017-0842-6

Keywords

  • Intercellular adhesion molecule-1 (ICAM-1)
  • Vascular cell adhesion molecule-1 (VCAM-1)
  • Vascular endothelial growth factor (VEGF)
  • Schizophrenia
  • Inflammation
  • Aging