Borderline personality disorder (BPD) is a severe mental disorder characterized by emotional dysregulation, impulsive behaviors, and difficulties in interpersonal relationships. Despite the poor understanding of the underlying biological processes, the oxytocin (OXT) system may be involved in and mediate some of BPD’s symptomatic and behavioral aspects. To clarify OXT’s role in BPD, we assessed its plasma levels and modulations induced by psychotherapies in patients.

Fifty BPD patients and 28 healthy controls (HC) participated in the study; patients were randomly assigned to two psychotherapeutic treatments: metacognitive interpersonal therapy and structured clinical management. Clinical and psychometric measures were assessed, and plasma was collected at baseline (T0) and in patients after 6 (T6) and 12 (T12) months of treatment. OXT was quantified by a radioimmunoassay technique.

BPD patients showed lower plasma OXT at T0 than HC (p = 0.002), and a correlation was observed (r = −0.36, p = 0.017) between low OXT concentrations and high Attachment Style Questionnaire – Italian Version–Preoccupation with Relationships subscale scores. OXT changed significantly over time in patients (p = 0.049) with an increase particularly evident from baseline to T6 (p = 0.022), without significant difference between treatment groups. OXT changes (T0 − T12) inversely correlated with symptom improvement as changes in the Zanarini Rating Scale for borderline personality disorder (r = 0.387, p = 0.006) and the Difficulties in Emotion Regulation Scale (r = 0.387, p = 0.005) scores during treatment.

OXT alteration in BPD patients and the regularizing effect of long-term psychotherapies support an involvement of the OXT system in the disease and in treatment impact. More research is needed to fully understand the underlying causal mechanisms linking OXT with pathogenesis and psychotherapy outcomes.