Kappa Opioid Receptor Availability in Borderline Personality Disorder: An In Vivo Investigation With [¹¹C]EKAP...

Borderline personality disorder (BPD) is a chronic mental health condition associated with marked elevations in disability. Limited pharmacological treatment options are currently available, and kappa opioid receptors (KORs) have been identified as a promising treatment target. However, the KOR system has not yet been directly examined in BPD. In this study, we examined KORs in individuals with BPD and investigated links between KORs and BPD's clinical features.

Twenty individuals with BPD and 20 demographically matched healthy control (HC) volunteer participants were scanned with [¹¹C]EKAP positron emission tomography (PET) and completed self-report and interview measures. KOR availability (volume of distribution [V_T]) was measured in brain regions of interest (ROIs) relevant to the pathophysiology of BPD.

No differences in age or sex were observed between HC participants (mean [SD] age = 32.94 [8.45], 60% female) and individuals with BPD (mean [SD] age = 33.30 [9.34], 60% female). In individuals with BPD, KOR V_T was significantly lower in the amygdala (mean difference [mean_diff] = -8.04, 95% CI [11.40 to -4.69]), anterior cingulate (mean_diff = -2.95, 95% CI [-5.22 to -0.68]); hippocampus (mean_diff = -2.12, 95% CI [-3.37 to -0.88]), insula (mean_diff = -3.58, 95% CI [-5.71 to -1.46]), and frontal ROIs (mean_diff = -1.83; 95% CI [-3.28 to -0.38]). V_T correlated negatively with specific clinical features including impulsivity (r₂₈ = -0.45 p = .013, 95% CI [-0.72 to -0.11]) and depressive symptoms (r₂₈ = -0.43, p = .021, 95% CI [-0.70 to -0.07]) but not with trauma symptoms.

The findings demonstrate differences in KOR availability in BPD and relationships between KOR availability and clinically relevant features. Results highlight the relevance of KOR in BPD pathophysiology and further implicate the opioid system as a promising target for treatment development in BPD.