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Abstract: Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy.
Fuente: Brain, Behavior and Immunity, 2021, 91, 673-682
Fecha de publicación: 01/01/2021
Nº de páginas: 10
Tipo de publicación: Artículo de Revista
Proyecto español: SAF2016-76046-R
Url de la publicación: https://doi.org/10.1016/j.bbi.2020.07.043
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LAGO, SANTIAGO G.
REES, GEERTJE F. VAN
GONZALEZ VIOQUE, EMILIANO
RAMSEY, JORDAN M.
BROEK, JANTINE A.
JAVIER VAZQUEZ BOURGON
SUAREZ PINILLA, PAULA
BARON COHEN, SIMON
BENEDICTO CRESPO FACORRO