ArticleFrontiers in psychiatry2021
Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder.
Article in Frontiers in psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Cognitive Decline and Illness Progression in Bipolar Disorder.Advances in therapy · 2026Pooled it
- Semaglutide Treatment of Antipsychotic-Treated Patients With Schizophrenia, Prediabetes, and Obesity: The HISTORI Randomized Clinical Trial.JAMA psychiatry · 2025Trial
- Role of the Blood-Brain Barrier in the Pathophysiology of Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A Comparative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Sodium-Glucose Cotransporter 2 Inhibitors and Dementia Risk in Patients With Psychiatric Disorders.JAMA network open · 2026Article
- Managing metabolic syndrome in bipolar disorder: multidisciplinary monitoring and treatment strategies.Frontiers in psychiatry · 2026Review
- Differential microRNA profiling of blood L1CAM and bulk extracellular vesicles in bipolar disorder.Epigenomics · 2025Article
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular sciences · 2025Review
- GLP-1 Receptor Agonists in Mood Disorders: A Psychiatric Perspective.Life (Basel, Switzerland) · 2025Review
- A systematic review on type 3 diabetes: bridging the gap between metabolic dysfunction and Alzheimer's disease.Diabetology & metabolic syndrome · 2025Review
- Genetic insights into the effect of Metformin on psychiatry disorders.European archives of psychiatry and clinical neuroscience · 2025Article
- Novel Insights into the Mechanism and Treatment of Diabetes-Related Brain Complications: Focusing on the Blood-Brain Barrier Impairment.Aging and disease · 2025Review
- Specific immune-inflammatory profiles and neurocognitive deficits predict illness trajectories in people with type 2 diabetes mellitus or psychiatric disorders.Brain, behavior, & immunity - health · 2025Article
- Association between fasting blood glucose and psychotic symptoms in Chinese patients with first-episode drug-naïve major depressive disorder.BMC psychiatry · 2025Article
- ENPP1 induces blood-brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer.Neuro-oncology · 2025Article
- Understanding immune system dysfunction and its context in mood disorders: psychoneuroimmunoendocrinology and clinical interventions.Military Medical Research · 2024Review
- Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives.Molecular neurobiology · 2024Review
- From spreading depolarization to blood-brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy.Nature reviews. Neurology · 2024Review
- Electroretinographic dysfunction, insulin resistance, and childhood trauma in early-course psychosis: A case-control exploratory study.Biomarkers in neuropsychiatry · 2024Article
- Review
- The metabolic overdrive hypothesis: hyperglycolysis and glutaminolysis in bipolar mania.Molecular psychiatry · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bipolar disorder (BD) often progresses to a more chronic and treatment resistant (neuroprogressive) course. Identifying which patients are at risk could allow for early intervention and prevention. Bipolar disorder is highly comorbid with metabolic disorders including type II diabetes mellitus (T2DM), hypertension, obesity, and dyslipidemia. Our studies have shown that insulin resistance (IR) is present in over 50% of patients with BD and that IR might underlie the progression of BD. While no confirmed predictors exist for identifying which patients with BD are likely to develop a more chronic course, emerging evidence including our own studies suggest that IR and related inflammatory pathways lead to impairments in blood-brain barrier (BBB) functioning. For the first time in living psychiatric patients, we have shown that the severity of BBB leakage is proportional to BD severity and is associated with IR. In this hypothesis paper we (i) highlight the evidence for a key role of IR in BD, (ii) show how IR in BD relates to shared inflammatory pathways, and (iii) hypothesize that these modulations result in BBB leakage and worse outcomes in BD. We further hypothesize that (iv) reversing IR through lifestyle changes or the actions of insulin sensitizing medications such as metformin, or optimizing BBB function using vascular protective drugs, such as losartan, could provide novel strategies for the prevention or treatment of neuroprogressive BD.
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