Christos Nousis

1. Moments of silence in the consulting room may be perceived as either comforting or unsettling by both patients and therapists. Despite its ubiquity in psychoanalytic work, silence remains a clin...

Borderline personality disorder (BPD) is a complex and heterogeneous condition characterized by emotional instability, impulsivity, and impaired regulation of interpersonal relationships. This narrative review integrates findings from recent neuroimaging, neurochemical, and treatment studies to identify core neurobiological mechanisms and highlight translational potential. Evidence from 112 studies published up to 2025 is synthesized, encompassing structural MRI, resting-state and task-based functional MRI, EEG, PET, and emerging machine learning applications. Consistent disruptions are observed across the prefrontal–amygdala circuitry, the default mode network (DMN), and mentalization-related regions. BPD shows a dominant and stable pattern of hyperconnectivity in the precuneus. Transdiagnostic comparisons with PTSD and cocaine use disorder (CUD) suggest partial overlap in DMN dysregulation, though BPD-specific traits emerge in network topology. Machine learning models achieve a classification accuracy of 70–88% and may support the tracking of early treatment responses. Longitudinal fMRI studies indicate that psychodynamic therapy facilitates the progressive normalization of dorsal anterior cingulate cortex (dACC) activity and reductions in alexithymia. We discuss the role of phenotypic heterogeneity (internalizing versus externalizing profiles), the potential of neuromodulation guided by biomarkers, and the need for standardized imaging protocols. Limitations include small sample sizes, a lack of effective connectivity analyses, and minimal multicenter cohort representation. Future research should focus on constructing multimodal biomarker panels that integrate functional connectivity, epigenetics, and computational phenotyping. This review supports the use of a precision psychiatry approach for BPD by aligning neuroscience with scalable clinical tools.

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—particularly DBT, psychodynamic therapy, and trauma-informed care—are essential. Future research should prioritise interdisciplinary, longitudinal studies to further bridge the gap between neurobiological findings and clinical innovation.

Background/Objectives: Borderline personality disorder (BPD) is a complex psychiatric condition marked by emotional dysregulation, interpersonal instability, and impulsivity. Despite the advances in psychotherapy and pharmacotherapy, many patients show a partial or unstable response. Recent research suggests that oxytocin, a neuropeptide involved in social cognition and emotional regulation, may offer novel therapeutic avenues. Methods: We systematically synthesize evidence from PubMed, PsycINFO, Web of Science, and Google Scholar on oxytocin’s role in BPD, prioritizing studies on neurobiology, emotion regulation, clinical interventions, and adjunctive therapy models. Thirty studies were included and critically appraised using PRISMA and Cochrane’s tools. Due to methodological heterogeneity, no meta-analysis was conducted; instead, the findings were integrated through a narrative synthesis approach. Results: Evidence supports oxytocin’s modulatory effects on amygdala reactivity, prefrontal–limbic connectivity, and hypothalamic–pituitary–adrenal axis function. Intranasal oxytocin appears beneficial for emotional regulation and interpersonal sensitivity, particularly in individuals with early trauma. The reported effect sizes ranged from small (Cohen’s d ≈ 0.40) to large (d ≈ 0.83), though some trials reported null or adverse effects, such as increased hypermentalization. Heterogeneous responses were influenced by factors such as sex, trauma history, and OXTR gene variants. Conclusions: Although intranasal oxytocin shows promise in modulating core neurobiological systems implicated in BPD and enhancing emotion regulation and social cognition, its clinical effects remain variable and context-dependent. The evidence supports cautious exploration of oxytocin as an adjunct to psychotherapeutic interventions rather than as a standalone treatment. Future research should focus on biomarker-informed, stratified trials that account for trauma history, genetic variation, and sex differences to clarify its therapeutic potential.