RT Journal Article
T1 Exploring cellular markers of metabolic syndrome in peripheral blood mononuclear cells across the neuropsychiatric spectrum.
A1 Lago, Santiago G
A1 Tomasik, Jakub
A1 van Rees, Geertje F
A1 Rubey, Marina
A1 Gonzalez-Vioque, Emiliano
A1 Ramsey, Jordan M
A1 Haenisch, Frieder
A1 Broek, Jantine A
A1 Vázquez-Bourgon, Javier
A1 Papiol, Sergi
A1 Suarez-Pinilla, Paula
A1 Ruland, Tillmann
A1 Auyeug, Bonnie
A1 Mikova, Olya
A1 Kabacs, Nikolett
A1 Arolt, Volker
A1 Baron-Cohen, Simon
A1 Crespo-Facorro, Benedicto
A1 Bahn, Sabine
K1 Antipsychotic treatment
K1 Cell surface marker
K1 Flow cytometry
K1 Homeostasis model assessment
K1 Insulin sensitivity
K1 Metabolic syndrome
K1 Neuropsychiatric conditions
K1 Peripheral blood mononuclear cell
K1 Polygenic risk score
K1 Response prediction
K1 Weight gain
AB 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.
YR 2020
FD 2020-09-06
LK http://hdl.handle.net/10668/16227
UL http://hdl.handle.net/10668/16227
LA en
DS RISalud
RD Apr 6, 2025