{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:37:36Z","timestamp":1785206256407,"version":"3.55.0"},"reference-count":75,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNICEF Greece Country Office"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Borderline personality disorder (BPD) is a severe psychiatric condition characterised by emotional instability, impulsivity, interpersonal dysfunction, and self-injurious behaviours. Despite growing clinical interest, the neuropsychological mechanisms underlying these symptoms are still not fully understood. This review aims to summarise findings from neuroimaging, psychophysiological, and neurodevelopmental studies in order to clarify the neurobiological and physiological basis of BPD, with a particular focus on emotional dysregulation and implications for the treatment of adolescents. Methods: A narrative review was conducted, integrating results from longitudinal neurodevelopmental studies, functional and structural neuroimaging research (e.g. FMRI and PET), and psychophysiological assessments (e.g., heart rate variability and cortisol reactivity). Studies were selected based on their contribution to understanding the neural correlates of BPD symptom dimensions, particularly emotion dysregulation, impulsivity, interpersonal dysfunction, and self-harm. Results: Findings suggest that early reductions in amygdala volume, as early as age 13 predict later BPD symptoms. Hyperactivity of the amygdala, combined with hypoactivity in the prefrontal cortex, underlies deficits in emotion regulation. Orbitofrontal abnormalities correlate with impulsivity, while disruptions in the default mode network and oxytocin signaling are related to interpersonal dysfunction. Self-injurious behaviour appears to serve a neuropsychological function in regulating emotional pain and trauma-related arousal. This is linked to disruption of the hypothalamic-pituitary-adrenal (HPA) axis and structural brain alterations. The Unified Protocol for Adolescents (UP-A) was more effective to Mentalization-Based Therapy for Adolescents (MBT-A) at reducing emotional dysregulation compared, though challenges in treating identity disturbance and relational difficulties remain. Discussion: The reviewed evidence suggests that BPD has its in early neurodevelopmental vulnerability and is sustained by maladaptive neurophysiological processes. Emotional dysregulation emerges as a central transdiagnostic mechanism. Self-harm may serve as a strategy for regulating emotions in response to trauma-related neural dysregulation. These findings advocate for the integration of neuroscience into psychotherapeutic practice, including the application of neuromodulation techniques and psychophysiological monitoring. Conclusions: A comprehensive understanding of BPD requires a neuropsychologically informed framework. Personalised treatment approaches combining pharmacotherapy, brain-based interventions, and developmentally adapted psychotherapies\u2014particularly DBT, psychodynamic therapy, and trauma-informed care\u2014are essential. Future research should prioritise interdisciplinary, longitudinal studies to further bridge the gap between neurobiological findings and clinical innovation.<\/jats:p>","DOI":"10.3390\/jcm14144973","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"4973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Wired for Intensity: The Neuropsychological Dynamics of Borderline Personality Disorders\u2014An Integrative Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1672-4727","authenticated-orcid":false,"given":"Eleni","family":"Giannoulis","sequence":"first","affiliation":[{"name":"Laboratory of Psychometrics and Neuropsychology, Eginition Hospital, Medical School of Athens, 11528 Athens, Greece"},{"name":"Specific Sector of Personality Disorders, Eginition Hospital, Medical School of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Nousis","sequence":"additional","affiliation":[{"name":"Laboratory of Psychometrics and Neuropsychology, Eginition Hospital, Medical School of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Krokou","sequence":"additional","affiliation":[{"name":"Laboratory of Psychometrics and Neuropsychology, Eginition Hospital, Medical School of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ifigeneia","family":"Zikou","sequence":"additional","affiliation":[{"name":"Laboratory of Psychometrics and Neuropsychology, Eginition Hospital, Medical School of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6078-5231","authenticated-orcid":false,"given":"Ioannis","family":"Malogiannis","sequence":"additional","affiliation":[{"name":"Specific Sector of Personality Disorders, Eginition Hospital, Medical School of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (APA) (2013). 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