Metformin’s Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1783 - 1783

Published: Feb. 19, 2025

This study examines the effects of metformin on brain functions focusing variability results reported in literature. While some studies suggest that may have neuroprotective diabetic patients, others report an insignificant impact cognitive function, or even a negative effect. We propose this inconsistency be due to intrinsic cellular-level among individuals, which we term "biovariance". Biovariance persists demographically homogeneous samples complex and stochastic biological processes. Additionally, metabolic actions metformin, including its influence neuroenergetics neuronal survival, produce different depending individual characteristics.

Language: Английский

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Local patterns of genetic sharing challenge the boundaries between neuropsychiatric and insulin resistance-related conditions

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Abstract The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a complex public health challenge. Evidence the genetic links between these phenotypes emerging, but little currently known about genomic regions and biological functions that are involved. To address this, we performed Local Analysis [co]Variant Association (LAVA) using large-scale (N=9,725-933,970) genome-wide association studies (GWASs) results for three IR-related (type 2 diabetes mellitus, obesity, syndrome) nine disorders. Subsequently, positional expression quantitative trait locus (eQTL)-based gene mapping downstream functional analyses were on significant loci. Patterns negative positive local correlations (|r g |=0.21-1, p FDR <0.05) identified at 109 unique across all phenotype pairs. emerged even in absence global Alzheimer’s disease, bipolar disorder, Tourette’s syndrome. Genes mapped to correlated showed enrichment pathways integral immune-inflammatory function, vesicle trafficking, signalling, oxygen transport, lipid metabolism. Colocalisation further prioritised 10 genetically likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants found within close proximity genes, such as SLC39A8 HLA-DRB1 , can be targeted by supplements already drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, cholesterol-lowering drugs. Overall, our findings underscore landscape IR-neuropsychiatric multimorbidity, advocating an integrated disease model offering novel insights research treatment strategies this domain. Highlights correlations. Both Enrichment immune, signalling pathways, among others. Pinpointed regions. Identified therapeutic targets, e.g., HLA-DRB1, drug repurposing.

Language: Английский

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Treatment of antipsychotic-induced hyperprolactinemia: an umbrella review of systematic reviews and meta-analyses

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: March 5, 2024

Background Hyperprolactinemia is a common antipsychotic-induced adverse event in psychiatric patients, and the quality of clinical studies investigating best treatments has varied. Thus, to better summarize evidence, we performed an umbrella review overlapping systematic reviews meta-analyses for treatment hyperprolactinemia. Methods The PubMed, Cochrane Library, PsycINFO, Scopus EMBASE were searched, meeting our inclusion criteria selected. Relevant data extracted, was conducted all included meta-analyses. assessed by using PRISMA scores AMSTAR 2 evaluation. Finally, evidence appropriate summarized discussed. Results Five published between 2013 2020 met requirements this review. ranged from 19.5–26. evaluation showed that 5 low 3 very quality. provide adding aripiprazole or dopamine agonist can effectively safely improve Two also adjunctive metformin reduce serum prolactin level, but more trials are needed confirm finding. Conclusion Adjunctive agonists have been proven be effective safe Among researched treatments, may most appropriate.

Language: Английский

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Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(12), P. 1714 - 1714

Published: Dec. 11, 2023

Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention its potential neuroprotective properties due to the growing demand treatments Alzheimer's, Parkinson's, and motor neuron diseases. This review synthesizes experimental clinical studies on metformin's mechanisms of action therapeutic benefits neurodegenerative disorders. A comprehensive search electronic databases, including PubMed, MEDLINE, Embase, Cochrane library, focused key phrases such as "metformin", "neuroprotection", "neurodegenerative diseases", with data up September 2023. Recent research glucoregulatory reveals new molecular targets, activation LKB1-AMPK signaling pathway, which is crucial chronic administration metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. precise role respiratory chain complexes (I IV), mitochondrial or lysosomes in metformin effects remains be established by further research. Research extrahepatic targets like gut microbiota, well antioxidant immunomodulatory properties, understanding Experimental animal models shows promising results, but inconclusive. Understanding could help design trials explore and, hopefully, prove conditions.

Language: Английский

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Metformin for neurocognitive dysfunction in schizophrenia: a systematic review

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

Background The efficacy and safety of metformin for addressing neurocognitive dysfunction in schizophrenia remain inconclusive. This systematic review evaluates the evidence from randomized controlled trials (RCTs) on effects function patients with schizophrenia. Methods A comprehensive search Chinese databases (WanFang, Journal Net) English (PubMed, EMBASE, PsycINFO, Cochrane Library) was conducted to identify RCTs assessing metformin’s impact outcomes Results Four involving 271 were included. Three (75%) demonstrated significant improvements compared controls, as assessed by MATRICS Consensus Cognitive Battery, Repeatable Battery Assessment Neuropsychological Status, Mini-Mental State Examination, but not Brief Cognition Schizophrenia. Two (50%) evaluated metformin's total psychopathology found no differences between groups. Adverse events reported two RCTs, inconsistent findings decreased appetite diarrhea. Other adverse discontinuation rates comparable Conclusion Preliminary suggests that may improve However, further large-scale, double-blind, high quality are warranted validate these findings.

Language: Английский

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Evaluating the efficacy of metformin in reducing hyperprolactinemia among patients with schizophrenia: A meta-analysis of randomized controlled trials

Journal of Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Background: Antipsychotic treatment is commonly associated with hyperprolactinemia, leading to menstrual disturbances, sexual dysfunction, and decreased bone mineral density. Nearly all antipsychotic drugs can elevate prolactin levels, affecting up 70% of patients schizophrenia. We aim evaluate the potential therapeutic role metformin in reducing hyperprolactinemia among these patients. Methods: systematically searched PubMed, CNKI, Embase, Cochrane, Web Science through January 31, 2024, for randomized controlled trials (RCTs) evaluating metformin’s effect on levels Data were extracted synthesized using random-effects meta-analysis. Results: This meta-analysis included 10 RCTs 1046 participants (584 received 462 placebo or no treatment). Metformin significantly reduced compared control groups (SMD = −0.98, 95% CI: −1.62, −0.35, p 0.002; transformed MD −34.88 ng/mL, −57.65, −12.46). Subgroup analyses indicated that higher doses (1500 mg), shorter durations (<24 weeks), BMI (>25 kg/m²), longer illness duration (>1 year) more significant reductions. was well tolerated increase adverse events all-cause discontinuation rates group. Conclusion: suggests shows as a antipsychotic-induced favorable tolerability profile schizophrenia, particularly at doses, durations, BMI, duration. Despite robustness findings, high heterogeneity necessitates cautious interpretation. Future research should explore demographic clinical factors influencing response optimizing treatment.

Language: Английский

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Overview of Metformin and Neurodegeneration: A Comprehensive Review

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 486 - 486

Published: March 28, 2025

This comprehensive review examines the therapeutic potential of metformin, a well-established diabetes medication, in treating neurodegenerative disorders. Originally used as first-line treatment for type 2 diabetes, recent studies have begun investigating metformin’s effects beyond metabolic disorders, particularly its neuroprotective capabilities against conditions like Parkinson’s disease, Alzheimer’s Huntington’s and multiple sclerosis. Key findings demonstrate that operate through pathways: AMPK activation enhancing cellular energy metabolism autophagy; upregulation antioxidant defenses; suppression inflammation; inhibition protein aggregation; improvement mitochondrial function. These mechanisms collectively address common pathological features neurodegeneration neuroinflammation, including oxidative stress, accumulation, dysfunction. Clinical preclinical evidence supporting association with improved cognitive performance, reduced risk dementia, modulation hallmarks diseases is critically evaluated. While metformin shows promise agent, this emphasizes need further investigation to fully understand optimal applications diseases.

Language: Английский

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Local patterns of genetic sharing between neuropsychiatric and insulin resistance-related conditions

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 12, 2025

The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a major public health challenge. Evidence the genetic links between these phenotypes emerging, but little currently known about genomic regions and biological functions that are involved. To address this, we performed Local Analysis [co]Variant Association (LAVA) using large-scale (N = 9,725-933,970) genome-wide association studies (GWASs) results for three IR-related (type 2 diabetes mellitus, obesity, syndrome) nine disorders. Subsequently, positional expression quantitative trait locus (eQTL)-based gene mapping downstream functional analyses were on significant loci. Patterns negative positive local correlations (|rg| 0.21-1, pFDR < 0.05) identified at 109 unique across all phenotype pairs. emerged even in absence global Alzheimer's disease, bipolar disorder, Tourette's syndrome. Genes mapped to correlated showed enrichment pathways integral immune-inflammatory function, vesicle trafficking, signalling, oxygen transport, lipid metabolism. Colocalisation further prioritised 10 genetically likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants found within close proximity genes, such as SLC39A8 HLA-DRB1, can be targeted by supplements already drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, cholesterol-lowering drugs. Overall, our findings highlight complex architecture IR-neuropsychiatric multimorbidity, advocating an integrated disease model offering novel insights research treatment strategies this domain.

Language: Английский

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Is There a Link Between Type 2 Diabetes Mellitus and Negative Symptoms in Schizophrenia? A Scoping Review

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(5), P. 499 - 499

Published: May 13, 2025

Background/Objectives: Type 2 diabetes mellitus (T2DM) and impaired glucose metabolism are more prevalent among patients with schizophrenia than in the general population. The incidence of T2DM is associated lifestyle factors that often influenced by negative symptoms schizophrenia; comorbid may contribute to reduced life expectancy observed schizophrenia. existing literature reveals a scarcity data regarding potential causal relationship between symptoms. Methods: A scoping review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews Meta-Analyses) criteria, utilizing PubMed database identify clinical studies investigating association (but not cognitive) symptom domain Subsequently, reference lists these identified publications were searched. Results: Seventeen included. There evidence supporting tolerance increased first-episode psychosis, several indicate poorer metabolic status correlates severe Patients chronic schizophrenia, however, had milder scores compared those without diabetes, although this less pronounced early disease stages. Conclusions: insufficient confirmatory causality on Further, preferably prospective needed explore complex potentially If found have or exacerbate pre-existing symptoms, it could lead significant changes therapeutic approaches

Language: Английский

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Dysregulation of energy metabolism in Alzheimer's disease

Journal of Neurology, Journal Year: 2024, Volume and Issue: 272(1)

Published: Dec. 2, 2024

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Its etiology and associated mechanisms are still unclear, which largely hinders development AD treatment strategies. Many studies have shown that dysregulation energy metabolism in brain closely related to development. Dysregulation with reduced glucose uptake utilization, altered insulin signaling pathways, mitochondrial dysfunction. In this study, we summarized relevant pathways regarding AD. addition, highlight possible role dysfunction as a central process. A deeper understanding relationship between may provide new insights for learning memory impairment patients improving prevention treatment.

Language: Английский

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