Virginie-Anne Chouinard , Wirya Feizi , Xi Chen , Boyu Ren , Kathryn E. Lewandowski , Jacey Anderson , Steven Prete , Emma Tusuzian , Kyle Cuklanz , Shuqin Zhou , Paula Bolton , Abigail Stein , Bruce M. Cohen , Fei Du , Dost Öngür
{"title":"在健康参与者中，鼻内胰岛素增加脑谷胱甘肽（GSH）并增强抗氧化能力，但在早期精神病患者中没有。","authors":"Virginie-Anne Chouinard , Wirya Feizi , Xi Chen , Boyu Ren , Kathryn E. Lewandowski , Jacey Anderson , Steven Prete , Emma Tusuzian , Kyle Cuklanz , Shuqin Zhou , Paula Bolton , Abigail Stein , Bruce M. Cohen , Fei Du , Dost Öngür","doi":"10.1016/j.bpsc.2024.11.018","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>We examined the acute effects of intranasal insulin on cognitive function and brain glutathione (GSH), a central factor in resistance to oxidative stress, in both participants with early psychosis and healthy control (HC) participants.</div></div><div><h3>Methods</h3><div>Twenty-one patients with early-stage psychotic disorders and 18 HC participants underwent magnetic resonance spectroscopy (MRS) scans and cognitive assessments before and after administration of intranasal insulin 40 IU. We conducted proton MRS (<sup>1</sup>H-MRS) in the prefrontal cortex at 4T to measure GSH and glutamate metabolites. We assessed cognition using the Brief Assessment of Cognition in Schizophrenia symbol coding, digit sequencing, and verbal fluency tasks, in addition to the Stroop task.</div></div><div><h3>Results</h3><div>The mean (SD) age of participants was 25.7 (4.6) years; 51.3% were female. There were no significant group differences at baseline in age, sex, body mass index, homeostatic model assessment of insulin resistance (HOMA-IR), or cognition. Patients had higher baseline GSH (<em>p</em> < .001) and glutamate (<em>p</em> = .007). After insulin administration, GSH increased in HC participants (mean change, 0.15; 95% CI 0.03 to 0.26; <em>p</em> = .015), but not in patients. Symbol coding improved in both patients (0.74; 95% CI 0.37 to 1.11; <em>p</em> < .001) and HC participants (0.83; 95% CI 0.58 to 1.09; <em>p</em> < .001), and verbal fluency improved in HC participants (0.43; 95% CI 0.14 to 0.72; <em>p</em> = .006). Lower baseline HOMA-IR was associated with greater change in GSH (coefficient −0.22; 95% CI −0.40 to −0.04; <em>p</em> = .017).</div></div><div><h3>Conclusions</h3><div>Intranasal insulin increased brain GSH in HC participants, but not in patients with early psychotic disorders. These novel findings demonstrate that intranasal insulin enhances antioxidant capacity and resilience to oxidative stress in HC individuals in contrast to an absent antioxidant response in those with early psychotic disorders.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 3","pages":"Pages 286-294"},"PeriodicalIF":5.7000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Intranasal Insulin Increases Brain Glutathione and Enhances Antioxidant Capacity in Healthy Participants but Not in Those With Early Psychotic Disorders\",\"authors\":\"Virginie-Anne Chouinard , Wirya Feizi , Xi Chen , Boyu Ren , Kathryn E. Lewandowski , Jacey Anderson , Steven Prete , Emma Tusuzian , Kyle Cuklanz , Shuqin Zhou , Paula Bolton , Abigail Stein , Bruce M. Cohen , Fei Du , Dost Öngür\",\"doi\":\"10.1016/j.bpsc.2024.11.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>We examined the acute effects of intranasal insulin on cognitive function and brain glutathione (GSH), a central factor in resistance to oxidative stress, in both participants with early psychosis and healthy control (HC) participants.</div></div><div><h3>Methods</h3><div>Twenty-one patients with early-stage psychotic disorders and 18 HC participants underwent magnetic resonance spectroscopy (MRS) scans and cognitive assessments before and after administration of intranasal insulin 40 IU. We conducted proton MRS (<sup>1</sup>H-MRS) in the prefrontal cortex at 4T to measure GSH and glutamate metabolites. We assessed cognition using the Brief Assessment of Cognition in Schizophrenia symbol coding, digit sequencing, and verbal fluency tasks, in addition to the Stroop task.</div></div><div><h3>Results</h3><div>The mean (SD) age of participants was 25.7 (4.6) years; 51.3% were female. There were no significant group differences at baseline in age, sex, body mass index, homeostatic model assessment of insulin resistance (HOMA-IR), or cognition. Patients had higher baseline GSH (<em>p</em> < .001) and glutamate (<em>p</em> = .007). After insulin administration, GSH increased in HC participants (mean change, 0.15; 95% CI 0.03 to 0.26; <em>p</em> = .015), but not in patients. Symbol coding improved in both patients (0.74; 95% CI 0.37 to 1.11; <em>p</em> < .001) and HC participants (0.83; 95% CI 0.58 to 1.09; <em>p</em> < .001), and verbal fluency improved in HC participants (0.43; 95% CI 0.14 to 0.72; <em>p</em> = .006). Lower baseline HOMA-IR was associated with greater change in GSH (coefficient −0.22; 95% CI −0.40 to −0.04; <em>p</em> = .017).</div></div><div><h3>Conclusions</h3><div>Intranasal insulin increased brain GSH in HC participants, but not in patients with early psychotic disorders. These novel findings demonstrate that intranasal insulin enhances antioxidant capacity and resilience to oxidative stress in HC individuals in contrast to an absent antioxidant response in those with early psychotic disorders.</div></div>\",\"PeriodicalId\":54231,\"journal\":{\"name\":\"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging\",\"volume\":\"10 3\",\"pages\":\"Pages 286-294\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2451902224003550\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2451902224003550","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Intranasal Insulin Increases Brain Glutathione and Enhances Antioxidant Capacity in Healthy Participants but Not in Those With Early Psychotic Disorders
Background
We examined the acute effects of intranasal insulin on cognitive function and brain glutathione (GSH), a central factor in resistance to oxidative stress, in both participants with early psychosis and healthy control (HC) participants.
Methods
Twenty-one patients with early-stage psychotic disorders and 18 HC participants underwent magnetic resonance spectroscopy (MRS) scans and cognitive assessments before and after administration of intranasal insulin 40 IU. We conducted proton MRS (1H-MRS) in the prefrontal cortex at 4T to measure GSH and glutamate metabolites. We assessed cognition using the Brief Assessment of Cognition in Schizophrenia symbol coding, digit sequencing, and verbal fluency tasks, in addition to the Stroop task.
Results
The mean (SD) age of participants was 25.7 (4.6) years; 51.3% were female. There were no significant group differences at baseline in age, sex, body mass index, homeostatic model assessment of insulin resistance (HOMA-IR), or cognition. Patients had higher baseline GSH (p < .001) and glutamate (p = .007). After insulin administration, GSH increased in HC participants (mean change, 0.15; 95% CI 0.03 to 0.26; p = .015), but not in patients. Symbol coding improved in both patients (0.74; 95% CI 0.37 to 1.11; p < .001) and HC participants (0.83; 95% CI 0.58 to 1.09; p < .001), and verbal fluency improved in HC participants (0.43; 95% CI 0.14 to 0.72; p = .006). Lower baseline HOMA-IR was associated with greater change in GSH (coefficient −0.22; 95% CI −0.40 to −0.04; p = .017).
Conclusions
Intranasal insulin increased brain GSH in HC participants, but not in patients with early psychotic disorders. These novel findings demonstrate that intranasal insulin enhances antioxidant capacity and resilience to oxidative stress in HC individuals in contrast to an absent antioxidant response in those with early psychotic disorders.
期刊介绍：
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is an official journal of the Society for Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of non-invasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The journal publishes novel results of original research which represent an important new lead or significant impact on the field. Reviews and commentaries that focus on topics of current research and interest are also encouraged.
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