title: Association of serum VEGF levels with prefrontal cortex volume in schizophrenia.
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.
authors.affiliation: Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta, GA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pillai
authors.affiliation: Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta, GA, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Howell
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, White Plains, NY, USA.
authors.forename: A O
authors.initials: AO
authors.lastname: Ahmed
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Weinberg
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Schizophrenia Research Institute, Sydney, NSW, Australia.
authors.forename: K M
authors.initials: KM
authors.lastname: Allen
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Schizophrenia Research Institute, Sydney, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Bruggemann
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Schizophrenia Research Institute, Sydney, NSW, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Lenroot
authors.affiliation: Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.|Northern Adelaide Local Health Network, Adelaide, SA, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.|Northern Adelaide Local Health Network, Adelaide, SA, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Galletly
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Schizophrenia Research Institute, Sydney, NSW, Australia.
authors.forename: C S
authors.initials: CS
authors.lastname: Weickert
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Schizophrenia Research Institute, Sydney, NSW, Australia.
authors.forename: T W
authors.initials: TW
authors.lastname: Weickert
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood* / Q000000981:diagnostic imaging* / Q000473:pathology; D012333:RNA, Messenger / Q000097:blood; D012559:Schizophrenia / Q000097:blood* / Q000000981:diagnostic imaging* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A