An In Vivo Examination of the Relationship Between Metabotropic Glutamate 5 Receptor and Suicide Attempts in People With Borderline Personality Disorder

Abstract

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 (V_T) 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.