An in vivo examination of the relationship between metabotropic glutamate receptor 5 and suicide attempts in people with borderline personality disorder.

Abstract

Background: Borderline Personality Disorder (BPD) is a serious psychiatric condition, associated with a high risk for suicide attempts and death by suicide. However, relatively little is known about the pathophysiology of BPD. The metabotropic glutamate receptor type 5 (mGlu5) has been specifically implicated in the pathophysiology of BPD and suicide attempts, with more general roles in emotion regulation, social and cognitive functioning, and pain processing. Here, we examined the relationship between mGlu5 availability, BPD, and suicide attempts in vivo for the first time.

Methods: Eighteen individuals with BPD, and 18 age-, sex-, and smoking-status matched healthy (HC) and 18 clinical comparison controls with major depressive disorder (MDD) completed comprehensive clinical assessments and participated in an [¹⁸F]FPEB positron emission tomography (PET) scan to measure mGlu5 availability. Volume of distribution (V_T) in the frontolimbic circuit implicated in BPD pathophysiology was the PET outcome measure.

Results: We observed significantly higher frontolimbic mGlu5 availability in BPD compared to both HC (p=.009, d=0.84, 18.43% difference), and MDD (p=.03, d=0.69, 15.21% difference). In the BPD, but not MDD group, higher mGlu5 availability was also associated with history of suicide attempts (SA; 19-25% higher, p's=.005-.02). Further, mGlu5 availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in BPD-SA group.

Conclusions: Results show higher mGlu5 availability in BPD and suicide attempt for the first time. Our preliminary findings suggest mGlu5 may be a critical treatment target for BPD symptoms, including suicide attempts, and warrant further investigation in larger samples.