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Exploring cellular markers of metabolic syndrome in peripheral blood mononuclear cells across the neuropsychiatric spectrum

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. Volume 91, January 2021, Pages 673-682

Editorial: Elsevier

 Fecha de publicación: 01/01/2021

Nº de páginas: 10

Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.bbi.2020.07.043

ISSN: 0889-1591,1090-2139

Proyecto español: SAF2016-76046-R

Url de la publicación: https://doi.org/10.1016/j.bbi.2020.07.043

Autores/as

LAGO, SANTIAGO G.

TOMASIK, JAKUB

REES, GEERTJE F. VAN

RUBEY, MARINA

GONZALEZ VIOQUE, EMILIANO

RAMSEY, JORDAN M.

HAENISCH, FRIEDER

BROEK, JANTINE A.

PAPIOL, SERGI

SUAREZ PINILLA, PAULA

RULAND, TILLMANN

AUYEUG, BONNIE

MIKOVA, OLYA

KABACS, NIKOLETT

AROLT, VOLKER

BARON COHEN, SIMON

BAHN, SABINE