title: Association of sFlt-1 and worsening psychopathology in relatives at high risk for psychosis: A longitudinal study.
abstract: Angiogenic dysfunction and abnormalities in psychopathology and brain structure have been reported in schizophrenia, but their relationships are mostly unknown. We recently demonstrated that sFlt-1, anti-angiogenic factor, was significantly elevated in patients at familial high-risk for psychosis (FHR). We hypothesized that elevated sFlt-1 correlates with baseline and longitudinal changes in psychopathology, cognition, and brain structure.
  
  
  
  Plasma sFlt-1 in FHR (n=35) and HC (n=39) was obtained at baseline. Schizotypal, cognitive, soft neurologic signs, and structural brain imaging (1.5T T1-weighted MRI, FreeSurfer software) measures were obtained in both groups. Longitudinal clinical and brain structural measures were obtained in a subgroup of FHR patients. Baseline data analysis used correlations between sFlt-1 and clinical/imaging measures and adjusted for multiple corrections. Linear mixed-effects models described differences in trajectories between high sFlt-1 and low sFlt-1.
  
  
  
  Baseline sFlt-1 was significantly correlated with soft neurologic signs (r=0.27, p=0.02) and right entorhinal volume (r=0.50, p=0.02), but not other baseline clinical/brain structural measures. Longitudinal examination of the FHR group (sFlt-1 high, n=14; sFlt-1 low, n=14) demonstrated that high sFlt-1 was significantly associated with worsening schizotypal symptoms (t=2.4, p=0.018). Reduced right hippocampal/parahippocampal volume/thickness trajectories were observed in high versus low sFlt-1 groups.
  
  
  
  The findings from this FHR study demonstrate that peripheral markers of angiogenic dysfunction can predict longitudinal clinical and brain structural changes. Also, these findings further support the hypothesis of altered microvascular circulation in schizophrenia and those at risk.
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, 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
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: 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, Beth Israel Deaconess Medical Center, Boston, MA, United States; Division of Public Psychiatry, Massachusetts Mental Health Center, Boston, MA, United States; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States. Electronic address: mkeshava@bidmc.harvard.edu.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood* / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D013223:Statistics as Topic; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenesis; Brain structure; Genetic high risk for psychosis; Longitudinal study; Microvascular; Soluble fms-like tyrosine kinase