BORDERLINE PERSONALITY DISORDER: MOLECULAR SIGNATURES LINKED TO PATHOLOGY AND PSYCHOTHERAPY EFFECTS

Background: Borderline Personality Disorder (BPD) is a severe mental disorder characterized by emotional dysregulation, impulsivity, and difficulties in interpersonal relationships. Despite its severity and prevalence, the underlying biological mechanisms that drive BPD pathophysiology remain poorly understood. Moreover, although it is known that psychotherapy is effective in symptom management, the biological effects of this type of treatment remain largely unexplored. This study builds upon the CLIMAMITHE project, a randomized clinical trial whose primary aim was to compare two psychotherapeutical approaches for BPD: Metacognitive Interpersonal Therapy (MIT) and Structured Clinical Management (SCM). Methods: 50 BPD patients and 26 non affected controls were recruited and clinical assessments were conducted to evaluate core symptoms such as emotional regulation, metacognition, and symptom severity. Patients were randomly assigned to MIT or SCM, both covering a period of 1 year. Blood samples were collected at the baseline, 6 months, and 12 months for patients, and at the baseline for controls. We then quantified molecular markers associated with key features of BPD, including: Oxytocin (OXT), β-endorphin, Brain-derived Neurotrophic Factor (BDNF), and microRNAs (miRNAs). Neuroimaging data were also available for the patient group. Results: Lower baseline OXT levels were found in BPD patients compared to controls. OXT levels increased during psychotherapy: this increment was correlated with clinical improvements in emotional regulation and BPD symptomatology. Also, OXT increase following psychotherapy negatively correlated with the decrease in the volume of the left anterior-inferior area of the hypothalamus. β-endorphin levels did not differ between patients and controls, nor any significant changes during psychotherapy were observed. Although non-significant, the T0-T12 increases of β-endorphin levels were positively correlated with the increase of the volume of the CA3 region of the hippocampus. BDNF levels were significantly higher in the group of patients, but psychotherapy was not able to modulate them. We also found a positive correlation between BDNF levels at T0 and the fractional anisotropy of the Ventral Default Mode Network and the Left Executive Control Network. Finally, eight miRNAs were differentially expressed between BPD patients and controls, and KEGG pathway analysis showed their involvement in pathways related to neuroplasticity and stress response. Conclusion: This study explored the role of molecular markers potentially involved in BPD, investigating their relationship with the pathology and the psychotherapies effect, highlighting alterations between patients and controls and, regarding OXT, also modulations induced by psychotherapies. Overall, these findings contribute to gain insight into the biological underpinnings of BPD, also providing potential novel markers that may be useful for the improvement of the differential diagnosis and the optimization of the therapeutic treatments for this disease.