Plasma β-III tubulin, neurofilament light chain and glial fibrillary acidic protein are associated with neurodegeneration and progression in schizophrenia

Daniela Rodrigues-Amorim, Tania Rivera-Baltanás, María Del Carmen Vallejo-Curto, Cynthia Rodriguez-Jamardo, Elena de Las Heras, Carolina Barreiro-Villar, María Blanco-Formoso, Patricia Fernández-Palleiro, María Álvarez-Ariza, Marta López, Alejandro García-Caballero, José Manuel Olivares, Carlos Spuch, Daniela Rodrigues-Amorim, Tania Rivera-Baltanás, María Del Carmen Vallejo-Curto, Cynthia Rodriguez-Jamardo, Elena de Las Heras, Carolina Barreiro-Villar, María Blanco-Formoso, Patricia Fernández-Palleiro, María Álvarez-Ariza, Marta López, Alejandro García-Caballero, José Manuel Olivares, Carlos Spuch

Abstract

Schizophrenia is a progressive disorder characterized by multiple psychotic relapses. After every relapse, patients may not fully recover, and this may lead to a progressive loss of functionality. Pharmacological treatment represents a key factor to minimize the biological, psychological and psychosocial impact of the disorder. The number of relapses and the duration of psychotic episodes induce a potential neuronal damage and subsequently, neurodegenerative processes. Thus, a comparative study was performed, including forty healthy controls and forty-two SZ patients divided into first-episode psychosis (FEP) and chronic SZ (CSZ) subgroups, where the CSZ sub group was subdivided by antipsychotic treatment. In order to measure the potential neuronal damage, plasma levels of β-III tubulin, neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) were performed. The results revealed that the levels of these proteins were increased in the SZ group compared to the control group (P < 0.05). Moreover, multiple comparison analysis showed highly significant levels of β-III tubulin (P = 0.0002), Nf-L (P = 0.0403) and GFAP (P < 0.015) in the subgroup of CSZ clozapine-treated. In conclusion, β-III tubulin, Nf-L and GFAP proteins may be potential biomarkers of neurodegeneration and progression in SZ.

Conflict of interest statement

Jose Manuel Olivares declared paid positions, honoraria and advisory boards by Angelini, AstraZeneca, Bristol-Myers, Casen Ricordati, GSK, Janssen, Lilly, Lundbeck, Novartis, Otsuka, Pfizer, Sanofi. The rest of the authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical course of schizophrenia. PFC: prefrontal cortex; FEP: first-episode of psychosis; DUP: duration of untreated psychosis.
Figure 2
Figure 2
Plasma levels of β-III tubulin, Nf-L and GFAP proteins in patients with SZ (N = 42) and controls (N = 40). Scatterplots of plasma levels of structural proteins. (a) Levels of β-III tubulin of patients with schizophrenia and controls (P < 0.0001). (b) Levels of Nf-L of patients with schizophrenia and controls (P = 0.0101). (c) Levels of GFAP of patients with schizophrenia and controls (P = 0.0212).
Figure 3
Figure 3
Plasma levels of β-III tubulin, Nf-L or GFAP in the subgroups of patients with SZ and controls. Scatterplots showing the levels of structural proteins by groups of patients with schizophrenia and the control group. (a) Scatterplot of levels of β-III tubulin that reveals statistical significance between clozapine-treated patients and control group (P = 0.0001). (b) Scatterplot of levels of Nf-L that showing a significant result between clozapine-treated patients and the control group (P = 0.0071). (c) Scatterplots of levels of GFAP, which demonstrates a significant correlation between clozapine-treated patients and controls (P = 0.0151). Full-length gels are presented in Supplementary Fig. 1.

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