Davis Margaret T, Asch Ruth H, Weiss Emily R, Wagner Ashley, Fineberg Sarah K, Nabulsi Nabeel, Matuskey David, Carson Richard E, Esterlis Irina
Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut; Department of Veteran Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, Connecticut.
Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Mar;10(3):324-332. doi: 10.1016/j.bpsc.2024.11.014. Epub 2024 Nov 28.
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) 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 availability, BPD, and SAs in vivo for the first time.
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 [F]FPEB positron emission tomography scan to measure mGlu availability. The volume of distribution (V) in the frontolimbic circuit implicated in BPD pathophysiology was the positron emission tomography outcome measure.
We observed significantly higher frontolimbic mGlu 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 mGlu availability was also associated with a history of SAs (19-25% higher, ps = .02-.005). Furthermore, mGlu availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in individuals with BPD and a history of SA.
Results show higher mGlu availability in BPD and SA for the first time. Our preliminary findings suggest that mGlu may be a critical treatment target for BPD symptoms, including SAs, and warrant additional investigation in larger samples.
边缘型人格障碍(BPD)是一种严重的精神疾病,与自杀未遂(SA)和自杀死亡的高风险相关。然而,关于BPD的病理生理学相对知之甚少。代谢型谷氨酸5受体(mGlu)已被特别认为与BPD和SA的病理生理学有关,在情绪调节、社会和认知功能以及疼痛处理中具有更广泛的作用。在这里,我们首次在体内研究了mGlu可用性、BPD和SA之间的关系。
18名BPD患者、18名年龄、性别和吸烟状况相匹配的健康对照参与者以及18名患有重度抑郁症的临床对照参与者完成了全面的临床评估,并参加了[F]FPEB正电子发射断层扫描以测量mGlu可用性。参与BPD病理生理学的额前脑回路中的分布容积(V)是正电子发射断层扫描的结果测量指标。
我们观察到BPD组的额前脑mGlu可用性显著高于健康对照组(p = 0.009,d = 0.84,差异18.43%)和重度抑郁症组(p = 0.03,d = 0.69,差异15.21%)。在BPD组而非重度抑郁症组中,较高的mGlu可用性也与SA病史相关(高19 - 25%,p值 = 0.02 - 0.005)。此外,mGlu可用性与有SA病史的BPD患者的自杀风险因素(如性侵害、感知到的负担感)呈正相关。
结果首次显示BPD和SA中mGlu可用性较高。我们的初步研究结果表明,mGlu可能是BPD症状(包括SA)的关键治疗靶点,值得在更大样本中进行进一步研究。