title: Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study.
abstract: Schizophrenia (SZ) is a heterogeneous disorder that presents in adolescence, persists into adulthood, and has many clinical features. Recent evidence suggests that abnormalities in inflammatory, neurotrophic, and angiogenic processes may play a role in the etiology of SZ. The identification of molecular biomarkers early in the course of disease is crucial to transforming diagnostic and therapeutic avenues. We investigated 14 molecular analytes focusing on inflammatory, neurotrophic and angiogenic pathways from the plasma of antipsychotic-naïve familial high risk for SZ (FHR; n=35) and first-episode psychosis (FEP; n=45) subjects, in comparison to healthy controls (HC, n=39). We identified distinct alterations in molecular signatures in young relatives at FHR for SZ prior to psychosis onset and FEP subjects. Firstly, the expression of soluble fms-like tyrosine kinase (sFlt-1), an anti-angiogenic factor that binds vascular endothelial growth factor (VEGF), was significantly increased in the FHR group compared to HC, but not in FEP. Secondly, interferon gamma (IFNγ) was significantly reduced in the FEP group compared to HC. Thirdly, network analysis revealed a positive correlation between sFlt-1 and VEGF, suggesting an activation of the angiogenic cascade in the FHR group, which persists in FEP. Our results indicate an angiogenesis and immunological dysfunction early in the course of disease, shifting the balance towards anti-angiogenesis and inflammation.
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States; Division of Public Psychiatry, Massachusetts Mental Health Center, Boston, MA, United States.
authors.forename: Paulo L
authors.initials: PL
authors.lastname: Lizano
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States; Division of Public Psychiatry, Massachusetts Mental Health Center, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States; Baylor College of Medicine, Houston, TX, United States.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tandon
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Mathew
authors.affiliation: Division of Public Psychiatry, Massachusetts Mental Health Center, Boston, MA, United States.
authors.forename: Suraj Sarvode
authors.initials: SS
authors.lastname: Mothi
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
authors.forename: Debra M
authors.initials: DM
authors.lastname: Montrose
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; VA Pittsburgh Healthcare System, Medical Research Service, Pittsburgh, PA, United States; Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, United States. Electronic address: jkyao@pitt.edu.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Yao
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D007371:Interferon-gamma; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenesis; First episode psychosis; High risk; Inflammation/immune; Soluble fms-like tyrosine kinase