ArticleEuropean psychiatry : the journal of the Association of European Psychiatrists2019
Insulin-signaling abnormalities in drug-naïve first-episode schizophrenia: Transduction protein analyses in extracellular vesicles of putative neuronal origin.
Article in European psychiatry : the journal of the Association of European Psychiatrists, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin.Journal of psychiatric research · 2021Trial
- From brain bioenergetics to hypothalamic glucoregulation: A shared-systems hypothesis for intrinsic dysglycemia in schizophrenia.Reviews in endocrine & metabolic disorders · 2026Review
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- An open-label study on ulotaront's effects on insulin-glucose regulation in schizophrenia patients with metabolic syndrome and prediabetes: Part I.Diabetes, obesity & metabolism · 2026Article
- Protein Kinase Expression of the AKT/mTOR Signaling Pathway in Peripheral Mononuclear Cells of Schizophrenia Patients: A Pilot Study.NeuroSci · 2025Article
- Characterizing longitudinal patterns of central and peripheral insulin resistance.Psychoneuroendocrinology · 2025Article
- Detection and Isolation of Tissue-Specific Extracellular Vesicles From the Blood.Journal of extracellular biology · 2025Review
- A systematic review of in vivo brain insulin resistance biomarkers in humans.Biomarkers in neuropsychiatry · 2025Review
- Exosomal Biomarkers: A Comprehensive Overview of Diagnostic and Prognostic Applications in Malignant and Non-Malignant Disorders.Biomolecules · 2025Review
- Potential of extracellular vesicle cargo as molecular signals in Schizophrenia: a scoping review.Schizophrenia (Heidelberg, Germany) · 2025Review
- A New Window to the Brain: Exosomes as a Promising Approach to Understand Mechanisms of Cognitive Deficits Associated With Obstructive Sleep Apnea.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2024Article
- Single-extracellular vesicle (EV) analyses validate the use of L1 Cell Adhesion Molecule (L1CAM) as a reliable biomarker of neuron-derived EVs.Journal of extracellular vesicles · 2024Article
- Review
- Extracellular vesicle biomarkers for complement dysfunction in schizophrenia.Brain : a journal of neurology · 2024Article
- Aerobic Exercise Improves the Overall Outcome of Type 2 Diabetes Mellitus Among People With Mental Disorders.Depression and anxiety · 2024Review
- Review
- Glucose Metabolism and Sex Hormones in Male Patients with Medication-naïve First-episode Schizophrenia: A Large-scale Cross-sectional Study.Current neuropharmacology · 2024Article
- Extracellular vesicle approach to major psychiatric disorders.European archives of psychiatry and clinical neuroscience · 2023Review
- The role of Extracellular Genomic Materials (EGMs) in psychiatric disorders.Translational psychiatry · 2023Review
- An NIMH Workshop on Non-Affective Psychosis in Midlife and Beyond: Research Agenda on Phenomenology, Clinical Trajectories, Underlying Mechanisms, and Intervention Targets.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2023Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundMetabolic syndrome and impaired insulin sensitivity may occur as side effects of atypical antipsychotic drugs. However, studies of peripheral insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) or oral glucose tolerance tests (OGTT) suggest that abnormal glucose metabolism is already present in drug-naive first-episode schizophrenia (DNFES). We hypothesized impairments of neuronal insulin signaling in DNFES.
methodsTo gain insight into neuronal insulin-signaling in vivo, we analyzed peripheral blood extracellular vesicles enriched for neuronal origin (nEVs). Phosphorylated insulin signal transduction serine-threonine kinases pS312-IRS-1, pY-IRS-1, pS473-AKT, pS9-GSK3β, pS2448-mTOR, pT389-p70S6K and respective total protein levels were determined in plasma nEVs from 48 DNFES patients and healthy matched controls after overnight fasting.
resultsUpstream pS312-IRS-1 was reduced at trend level (p = 0.071; this condition may amplify IRS-1 signaling). Exploratory omnibus analysis of downstream serine-threonine kinases (AKT, GSK3β, mTOR, p70S6K) revealed lower phosphorylated/total protein ratios in DNFES vs. controls (p = 0.013), confirming decreased pathway activation. Post-hoc-tests indicated in particular a reduced phosphorylation ratio of mTOR (p = 0.027). Phosphorylation ratios of p70S6K (p = 0.029), GSK3β (p = 0.039), and at trend level AKT (p = 0.061), showed diagnosis-dependent statistical interactions with insulin blood levels. The phosphorylation ratio of AKT correlated inversely with PANSS-G and PANSS-total scores, and other ratios showed similar trends.
conclusionThese findings support the hypothesis of neuronal insulin resistance in DNFES, small sample sizes notwithstanding. The counterintuitive trend towards reduced pS312-IRS-1 in DNFES may result from adaptive feedback mechanisms. The observed changes in insulin signaling could be clinically meaningful as suggested by their association with higher PANSS scores.
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Registered trials
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