Margaret T. Davis , Ruth H. Asch , Emily R. Weiss , Ashley Wagner , Sarah K. Fineberg , Nabeel Nabulsi , David Matuskey , Richard E. Carson , Irina Esterlis
{"title":"代谢性谷氨酸受体5与边缘型人格障碍患者自杀企图关系的体内研究。","authors":"Margaret T. Davis , Ruth H. Asch , Emily R. Weiss , Ashley Wagner , Sarah K. Fineberg , Nabeel Nabulsi , David Matuskey , Richard E. Carson , Irina Esterlis","doi":"10.1016/j.bpsc.2024.11.014","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Borderline personality disorder (BPD) is a serious psychiatric condition that is associated with a high risk for suicide attempts (SAs) and death by suicide. However, relatively little is known about the pathophysiology of BPD. The metabotropic glutamate 5 receptor (mGlu<sub>5</sub>) has been specifically implicated in the pathophysiology of BPD and SAs, with more general roles in emotion regulation, social and cognitive functioning, and pain processing. Here, we examined the relationship between mGlu<sub>5</sub> availability, BPD, and SAs in vivo for the first time.</div></div><div><h3>Methods</h3><div>Eighteen individuals with BPD, 18 healthy control participants matched on age, sex, and smoking status, and 18 clinical comparison control participants with major depressive disorder completed comprehensive clinical assessments and participated in an [<sup>18</sup>F]FPEB positron emission tomography scan to measure mGlu<sub>5</sub> availability. The volume of distribution (<em>V</em><sub>T</sub>) in the frontolimbic circuit implicated in BPD pathophysiology was the positron emission tomography outcome measure.</div></div><div><h3>Results</h3><div>We observed significantly higher frontolimbic mGlu<sub>5</sub> availability in the BPD group than in both the healthy control group (<em>p</em> = .009, <em>d</em> = 0.84, 18.43% difference) and the major depressive disorder group (<em>p</em> = .03, <em>d</em> = 0.69, 15.21% difference). In the BPD, but not the major depressive disorder group, higher mGlu<sub>5</sub> availability was also associated with a history of SAs (19–25% higher, <em>p</em>s = .02–.005). Furthermore, mGlu<sub>5</sub> availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in individuals with BPD and a history of SA.</div></div><div><h3>Conclusions</h3><div>Results show higher mGlu<sub>5</sub> availability in BPD and SA for the first time. Our preliminary findings suggest that mGlu<sub>5</sub> may be a critical treatment target for BPD symptoms, including SAs, and warrant additional investigation in larger samples.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 3","pages":"Pages 324-332"},"PeriodicalIF":5.7000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An In Vivo Examination of the Relationship Between Metabotropic Glutamate 5 Receptor and Suicide Attempts in People With Borderline Personality Disorder\",\"authors\":\"Margaret T. Davis , Ruth H. Asch , Emily R. Weiss , Ashley Wagner , Sarah K. Fineberg , Nabeel Nabulsi , David Matuskey , Richard E. Carson , Irina Esterlis\",\"doi\":\"10.1016/j.bpsc.2024.11.014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Borderline personality disorder (BPD) is a serious psychiatric condition that is associated with a high risk for suicide attempts (SAs) and death by suicide. However, relatively little is known about the pathophysiology of BPD. The metabotropic glutamate 5 receptor (mGlu<sub>5</sub>) has been specifically implicated in the pathophysiology of BPD and SAs, with more general roles in emotion regulation, social and cognitive functioning, and pain processing. Here, we examined the relationship between mGlu<sub>5</sub> availability, BPD, and SAs in vivo for the first time.</div></div><div><h3>Methods</h3><div>Eighteen individuals with BPD, 18 healthy control participants matched on age, sex, and smoking status, and 18 clinical comparison control participants with major depressive disorder completed comprehensive clinical assessments and participated in an [<sup>18</sup>F]FPEB positron emission tomography scan to measure mGlu<sub>5</sub> availability. The volume of distribution (<em>V</em><sub>T</sub>) in the frontolimbic circuit implicated in BPD pathophysiology was the positron emission tomography outcome measure.</div></div><div><h3>Results</h3><div>We observed significantly higher frontolimbic mGlu<sub>5</sub> availability in the BPD group than in both the healthy control group (<em>p</em> = .009, <em>d</em> = 0.84, 18.43% difference) and the major depressive disorder group (<em>p</em> = .03, <em>d</em> = 0.69, 15.21% difference). In the BPD, but not the major depressive disorder group, higher mGlu<sub>5</sub> availability was also associated with a history of SAs (19–25% higher, <em>p</em>s = .02–.005). Furthermore, mGlu<sub>5</sub> availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in individuals with BPD and a history of SA.</div></div><div><h3>Conclusions</h3><div>Results show higher mGlu<sub>5</sub> availability in BPD and SA for the first time. Our preliminary findings suggest that mGlu<sub>5</sub> may be a critical treatment target for BPD symptoms, including SAs, and warrant additional investigation in larger samples.</div></div>\",\"PeriodicalId\":54231,\"journal\":{\"name\":\"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging\",\"volume\":\"10 3\",\"pages\":\"Pages 324-332\"},\"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/S2451902224003513\",\"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/S2451902224003513","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
An In Vivo Examination of the Relationship Between Metabotropic Glutamate 5 Receptor and Suicide Attempts in People With Borderline Personality Disorder
Background
Borderline personality disorder (BPD) is a serious psychiatric condition that is associated with a high risk for suicide attempts (SAs) and death by suicide. However, relatively little is known about the pathophysiology of BPD. The metabotropic glutamate 5 receptor (mGlu5) has been specifically implicated in the pathophysiology of BPD and SAs, with more general roles in emotion regulation, social and cognitive functioning, and pain processing. Here, we examined the relationship between mGlu5 availability, BPD, and SAs in vivo for the first time.
Methods
Eighteen individuals with BPD, 18 healthy control participants matched on age, sex, and smoking status, and 18 clinical comparison control participants with major depressive disorder completed comprehensive clinical assessments and participated in an [18F]FPEB positron emission tomography scan to measure mGlu5 availability. The volume of distribution (VT) in the frontolimbic circuit implicated in BPD pathophysiology was the positron emission tomography outcome measure.
Results
We observed significantly higher frontolimbic mGlu5 availability in the BPD group than in both the healthy control group (p = .009, d = 0.84, 18.43% difference) and the major depressive disorder group (p = .03, d = 0.69, 15.21% difference). In the BPD, but not the major depressive disorder group, higher mGlu5 availability was also associated with a history of SAs (19–25% higher, ps = .02–.005). Furthermore, mGlu5 availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in individuals with BPD and a history of SA.
Conclusions
Results show higher mGlu5 availability in BPD and SA for the first time. Our preliminary findings suggest that mGlu5 may be a critical treatment target for BPD symptoms, including SAs, and warrant additional investigation in larger samples.
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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