Document Type : Review Article
Author
Master of Science in Chemical Engineering, Biotechnology, Islamic Azad University, North Tehran Branch, Tehran, Iran
Abstract
Background: Borderline Personality Disorder (BPD) is a severe and complex psychiatric illness characterized by pervasive instability in affect regulation, impulse control, interpersonal relationships, and self-image. While historically understood through psychosocial lenses, contemporary research has established a robust neurobiological foundation. This review synthesizes current evidence to provide an integrative model linking genetic predisposition, early environmental adversity, and alterations in brain structure, function, and neurochemistry.
Objectives: To systematically review and integrate evidence on the structural, functional, neurochemical, and genetic correlates of BPD, and to propose a coherent neurodevelopmental etiological model that explains core clinical symptoms.
Methods: A narrative review was conducted using PubMed, Scopus, and PsycINFO for literature published between 2005-2025. Search terms included "borderline personality disorder neurobiology," "BPD neuroimaging," "BPD genetics," and "fronto-limbic." Priority was given to meta-analyses, systematic reviews, and original research with robust methodology. Findings were synthesized thematically to construct an integrated model.
Results: Converging evidence confirms a primary dysfunction in fronto-limbic and salience networks, characterized by amygdala and insula hyperreactivity to emotional stimuli coupled with diminished prefrontal (especially orbitofrontal and anterior cingulate cortices) regulation. Structural alterations in these regions are prevalent. Neurochemically, dysfunction in serotonergic and oxytocinergic systems, alongside hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, are central. Significant gene-environment interactions (e.g., involving SLC6A4, FKBP5) mediate risk, with epigenetics providing a mechanism for the biological embedding of early trauma. Effective psychotherapies induce measurable neuroplastic changes, normalizing these dysfunctions.
Conclusions: BPD is best conceptualized as a neurodevelopmental disorder of emotion regulation and social cognition. A triple-network dysfunction model—involving hyperactive salience, underactive executive control, and altered default mode networks—effectively explains the core phenotype. This model unifies biological and psychosocial perspectives, reduces stigma, and directs future research toward circuit-based therapeutics and preventative interventions for at-risk individuals.
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