Peripheral β-Endorphin in Borderline Personality Disorder: Investigating Clinical Correlates and Longitudinal Changes During Psychotherapy

Borderline personality disorder (BPD) is characterized by emotion dysregulation, interpersonal dysfunction, and frequent non-suicidal self-injury (NSSI). Altered pain sensitivity in BPD has raised interest in the possible role of the endogenous opioid system, but only a few studies have explored β-endorphin, one of the major endogenous opioid peptides, in this disorder. Here we investigated serum β-endorphin levels in patients with BPD, their association with clinical features, and their longitudinal changes during psychotherapy. Forty-nine patients with BPD enrolled in the CLIMAMITHE randomized controlled trial and 25 age- and sex-matched unaffected controls were included. Serum β-endorphin concentrations were measured by ELISA at baseline in all participants and also after 6 and 12 months of treatment in patients receiving metacognitive interpersonal therapy or structured clinical management. Baseline β-endorphin levels did not differ between patients and controls and were not associated with symptom severity, interpersonal functioning, attachment style, psychotropic treatment, or NSSI. No overall longitudinal changes were observed during psychotherapy. However, responders showed a significant increase in β-endorphin levels from T0 to T12 (p = 0.016), whereas non-responders remained unchanged. Moreover, responders exhibited significantly lower baseline β-endorphin concentrations than non-responders (p = 0.001), and baseline levels showed potential discriminative value for treatment response (AUC = 0.806, p = 0.002) and correlated with changes in emotion dysregulation during treatment, measured through the DERS (r = 0.344, p = 0.040). In conclusion, these findings suggest that peripheral β-endorphin is unlikely to represent a trait biomarker of BPD but may be associated with response to psychotherapy, although its potential clinical relevance requires validation in larger independent cohorts.