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Abnormal levels of vascular endothelial biomarkers in schizophrenia

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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

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.

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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.

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Authors and 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

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Correspondence to Lisa T. Eyler.

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

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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

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