Coupled and decoupled fronto–cerebellar and affective brain networks characterize adolescents with borderline personality disorder

Introduction Previous work demonstrated that adolescents with borderline personality disorder (aBPD) exhibit gray and white matter density (GM) alterations in multiple regions, yet prior neuroimaging studies have predominantly examined GM and WM in isolation, limiting the ability to capture their joint neurodevelopmental alterations. The present study aims to overcome this limitation by integrating GM and WM structural features within a unified unsupervised multimodal data-fusion framework, in order to identify latent brain components reflecting shared and dissociable patterns and to relate these multimodal signatures to clinical and functional measures. We predicted that adolescents with BPD would show coupled and decoupled gray-white matter networks related to affective processing and executive functions. Methods High-resolution T1-weighted structural MRI data from 129 adolescents with borderline personality disorder (aged 12–17) and 107 age-, gender-, and education-matched healthy controls were analyzed using transposed independent vector analysis (tIVA-G), integrating gray and white matter features. Multiple clinical measures were collected and used to assess the clinical relevance of the identified multimodal components. In addition, decision tree models were applied to derive an interpretable predictive model discriminating adolescents with BPD from healthy controls. Results Two distinct structural components differentiating adolescents with BPD from healthy controls were identified. A first component (IC18) reflected a gray matter-driven pattern, characterized by reduced volume in a fronto-cerebellar loop, with no corresponding white matter contribution. A second component (IC5) captured a coupled gray matter–white matter alteration, showing increased gray matter in limbic–affective regions and Default network regions, including temporal and medial frontal areas, precuneus, and cerebellum, alongside reduced white matter in frontal regions. This network was significantly associated with greater emotion dysregulation, self-injurious behaviors, internalizing symptoms, and lower global functioning. Decision tree discriminated adolescents with BPD from healthy controls with moderate accuracy (71.7%). Conclusions Together, these multimodal patterns link large-scale brain organization to emotion dysregulation, self-injurious behaviors, and functional impairment in youth with BPD, providing a more comprehensive neurobiological account of the disorder and informing future biomarker-oriented and mechanistically grounded interventions.