Association of sFlt-1 and worsening psychopathology in relatives at high risk for psychosis: A longitudinal study

Background 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. Methods Plasma sFlt-1 in FHR (n = 35) and HC (n = 39) was obtained at baseline. Schizotypal, cognitive, soft neurologic signs, and structural brain imaging (1.5 T 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. Results 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. Conclusions 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.