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Association of serum VEGF levels with prefrontal cortex volume in schizophrenia

Molecular Psychiatry volume 21, pages 686–692 (2016)Cite this article

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Abstract

A large body of evidence indicates alterations in brain regional cellular energy metabolism and blood flow in schizophrenia. Among the different molecules regulating blood flow, vascular endothelial growth factor (VEGF) is generally accepted as the major factor involved in the process of angiogenesis. In the present study, we examined whether peripheral VEGF levels correlate with changes in the prefrontal cortex (PFC) volume in patients with schizophrenia and in healthy controls. Whole-blood samples were obtained from 96 people with schizophrenia or schizoaffective disorder and 83 healthy controls. Serum VEGF protein levels were analyzed by enzyme-linked immunosorbent assay, whereas quantitative PCR was performed to measure interleukin-6 (IL-6, a pro-inflammatory marker implicated in schizophrenia) mRNA levels in the blood samples. Structural magnetic resonance imaging scans were obtained using a 3T Achieva scanner on a subset of 59 people with schizophrenia or schizoaffective disorder and 65 healthy controls, and prefrontal volumes were obtained using FreeSurfer software. As compared with healthy controls, individuals with schizophrenia had a significant increase in log-transformed mean serum VEGF levels (t(177)=2.9, P=0.005). A significant inverse correlation (r=−0.40, P=0.002) between serum VEGF and total frontal pole volume was found in patients with schizophrenia/schizoaffective disorder. Moreover, we observed a significant positive association (r=0.24, P=0.03) between serum VEGF and IL-6 mRNA levels in patients with schizophrenia. These findings suggest an association between serum VEGF and inflammation, and that serum VEGF levels are related to structural abnormalities in the PFC of people with schizophrenia.

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Acknowledgements

We thank Loretta Moore, Nick Vella, Merribel Kyaw, Selena Hu, Alice Rothwell, Richard Morris, Ryan Balzan and Beverly Hisee for screening participants, performing cognitive and symptom assessments, data entry, management and monitoring. This work was supported by the University of New South Wales, the National Health and Medical Research Council (NHMRC) of Australia Project grant number 568807, Neuroscience Research Australia, the Schizophrenia Research Institute utilizing infrastructure funding from the NSW Ministry of Health and the Macquarie Group Foundation and the Australian Schizophrenia Research Bank, which is supported by the NHMRC of Australia, the Pratt Foundation, Ramsay Health Care and the Viertel Charitable Foundation. CSW is a recipient of a National Health and Medical Research Council (Australia) Senior Research Fellowship (1021970). AP acknowledges the Department of Psychiatry and Health Behavior, Georgia Regents University for financial support for this study.

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Author notes

  1. K R Howell

    Present address: 9Current address: Department of Psychiatry, University of Colorado Denver, School of Medicine, Aurora, CO, USA.,

  2. A Pillai and K R Howell: These authors are the co-first authors.

Authors and Affiliations

  1. Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta, GA, USA

    A Pillai & K R Howell

  2. Department of Psychiatry, Weill Cornell Medical College, White Plains, NY, USA

    A O Ahmed

  3. Neuroscience Research Australia, Sydney, NSW, Australia

    D Weinberg, K M Allen, J Bruggemann, R Lenroot, C S Weickert & T W Weickert

  4. School of Psychiatry, University of New South Wales, Sydney, NSW, Australia

    K M Allen, J Bruggemann, R Lenroot, C S Weickert & T W Weickert

  5. Schizophrenia Research Institute, Sydney, NSW, Australia

    K M Allen, J Bruggemann, R Lenroot, C S Weickert & T W Weickert

  6. Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia

    D Liu & C Galletly

  7. Northern Adelaide Local Health Network, Adelaide, SA, Australia

    D Liu & C Galletly

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Pillai, A., Howell, K., Ahmed, A. et al. Association of serum VEGF levels with prefrontal cortex volume in schizophrenia. Mol Psychiatry 21, 686–692 (2016). https://doi.org/10.1038/mp.2015.96

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