Grant: Project Grant

Borderline personality disorder (BPD) is a common and serious psychiatric illness that places a heavy burden on affected individuals, their families, and healthcare systems. Non-suicidal self-injury (NSSI), or the intentional destruction of bodily tissue, is a hallmark of BPD. High levels of anger often precede NSSI and are a potent risk factor for continued self-harm. We previously discovered that fatty acid amide hydrolase (FAAH), a component of the brain endocannabinoid system that dampens neural signaling, is elevated in the prefrontal cortex (PFC) of BPD assessed using positron emission tomography, a state-of-the-art brain imaging technique. We also found that PFC FAAH levels were correlated with a measure of anger in BPD. The present proposal seeks to understand whether high levels of FAAH in BPD can change in response to psychosocial interventions that treat anger and other clinical symptoms of BPD, such as NSSI. We are also interested in pursuing whether FAAH levels are increased in clinical disorders related to BPD, such as major depressive episodes (MDEs). Thus, we will also test FAAH binding in MDEs. We predict that we will find higher levels of FAAH in MDEs, because there are clinical similarities between BPD and MDEs. Finally, we will measure whether FAAH levels are increased in BPD+MDE compared with MDE alone to discover whether FAAH is elevated even further in comorbid conditions. These series of experiments will help discern whether FAAH is malleable to change, especially in relation to core features of BPD. They will also uncover whether similar disorders have the same pathology; if so, results would provide an impetus for developing new treatments that could ameliorate multiple psychiatric conditions. Ultimately, we hope to decrease the clinical burden associated with BPD, including anger, and reduce NSSI that contributes to the exceedingly high morbidity and mortality associated with BPD.