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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.

SUBMITTER: Lizano PL

PROVIDER: S-EPMC5432401 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Lizano Paulo L PL Yao Jeffrey K JK Tandon Neeraj N Mothi Suraj Sarvode SS Montrose Debra M DM Keshavan Matcheri S MS

Schizophrenia research 20161115

<h4>Background</h4>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.<h4>Methods</h4>Plasma sFlt-1 in FHR ( ...[more]

PMID: 27863935

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Project description:BackgroundElevated risk of psychotic disorders in migrant groups is a public mental health priority. We investigated whether living in areas of high own-region migrant density was associated with reduced risk of psychotic disorders among migrants and their children, and whether generation status, probable visible minority status, or region-of-origin affected this relationship.MethodsWe used the Swedish registers to identify migrants and their children born between Jan 1, 1982, and Dec 31, 1996, and living in Sweden on or after their 15th birthday. We tracked all included participants from age 15 years or date of migration until emigration, death, or study end (Dec 31, 2016). The outcome was an ICD-10 diagnosis of non-affective psychosis (F20-29). We calculated own-region and generation-specific own-region density within the 9208 small areas for market statistics neighbourhoods in Sweden, and estimated the relationship between density and diagnosis of non-affective psychotic disorders using multilevel Cox proportional hazards models, adjusting for individual confounders (generation status, age, sex, calendar year, lone dwelling, and time since migration [migrants only]), family confounders (family income, family unemployment, and social welfare), and neighbourhood confounders (deprivation index, population density, and proportion of lone dwellings), and using the Akaike information criterion (AIC) to compare model fit.FindingsOf 468 223 individuals included in the final cohort, 4582 (1·0%) had non-affective psychotic disorder. Lower own-region migrant density was associated with increased risk of psychotic disorders among migrants (hazard ratio [HR] 1·05, 95% CI 1·02-1·07 per 5% decrease) and children of migrants (1·03, 1·01-1·06), after adjustment. These effects were stronger for probable visible minority migrants (1·07, 1·04-1·11), including migrants from Asia (1·42, 1·15-1·76) and sub-Saharan Africa (1·28, 1·15-1·44), but not migrants from probable non-visible minority backgrounds (0·99, 0·94-1·04). Among migrants, adding generation status to the measure of own-region density provided a better fit to the data than overall own-region migrant density (AIC 36 103 vs 36 106, respectively), with a 5% decrease in generation-specific migrant density corresponding to a HR of 1·07 (1·04-1·11).InterpretationMigrant density was associated with non-affective psychosis risk in migrants and their children. Stronger protective effects of migrant density were found for probable visible minority migrants and migrants from Asia and sub-Saharan Africa. For migrants, this risk intersected with generation status. Together, these results suggest that this health inequality is socially constructed.FundingWellcome Trust, Royal Society, Mental Health Research UK, University College London, National Institute for Health Research, Swedish Research Council, and FORTE.

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

Publications

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

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