Abstract
Schizophrenia is thought to be a neurodevelopmental disorder with neuronal migration, differentiation and maturation disturbances. Tau is a microtubule-associated protein with a crucial role in these processes. Lower circulating tau levels have been reported in adults with schizophrenia, but this association has not been investigated in adolescent psychosis. We aimed to test the hypotheses that a) adolescents with early-onset psychosis (EOP; age of onset <18 years) display lower plasma tau concentrations compared to healthy controls, and b) among patients with psychosis, tau levels are linked to structural brain measures associated with the microtubule-associated tau (MAPT) gene and psychosis. We included 37 adolescent patients with EOP (mean age 16.4 years) and 59 adolescent healthy controls (mean age 16.2 years). We investigated putative patient-control differences in plasma total tau concentrations measured by a Single molecule array (Simoa) immunoassay. We explored the correlations between tau and selected structural brain measures based on T1-weighted MRI scans processed in FreeSurfer v6.0. We found significantly lower plasma tau concentrations in patients compared to healthy controls (p = 0.017, partial eta-squared = 0.061). Tau was not associated with antipsychotic use or the antipsychotic dosage. Among patients but not healthy controls, tau levels were positively correlated with the cortical orbitofrontal surface area (p = 0.013, R-squared = 0.24). The results are suggestive of a tau-related neurodevelopmental disturbance in adolescent psychosis.
Highlights
Schizophrenia affects roughly 1% of the human population and is a major cause of health burden and disability (Kahn et al, 2015; Salomon et al, 2012)
In the multivariate model, we explored the putative association between disease status (EOP vs. healthy controls (HC)) and logtau concentrations, whilst controlling for variables that differentiated pa tients from HC or were correlated with logtau in the bivariate analysis
The main finding of the present study was the lower circulating tau concentrations in adolescent patients with psychosis compared to HC (Fig. 1)
Summary
Schizophrenia affects roughly 1% of the human population and is a major cause of health burden and disability (Kahn et al, 2015; Salomon et al, 2012). Tau, discovered in 1975 (Weingarten et al, 1975), is an intracellular protein mostly present in nerve cells and in smaller amounts in glial cells (Wang and Mandelkow, 2016) It is a key microtubule-associated protein that binds to the microtubule network, regulates its organization and shields it against depolymerization (Barbier et al, 2019; Lasser et al, 2018; Wang and Mandelkow, 2016). If psychotic disorders are neurodevelopmental in nature, and circulating (plasma or serum) tau reflects early (pre- and perinatal) or later (during adolescence) developmental brain processes, we would expect lower circulating tau levels in patients with psychosis
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