Structural alterations related to emotion dysregulation, anxiety and self-harm in adolescents borderline personality disorder. A source-based morphometry study

Objective: Previous research suggests that adolescents with BPD (aBPD) exhibit distinct neuroanatomical alterations, although methodological limitations such as low sample size, and the reliance on univariate massive statistical analyses, prevent conclusions. Moreover, the possibility to associate these abnormalities with clinical features has been only partially explored. This study aims to investigate structural brain differences in the largest sample of adolescents with BPD to date, using a combination of unsupervised and supervised machine learning approaches: Source-Based Morphometry (SBM) and a deep neural network whose architecture was optimized through genetic algorithms. We hypothesize that adolescents with BPD will exhibit increased gray matter volume in the default mode network (DMN) and cerebellum, strictly related with emotion dysregulation and borderline symptoms, alongside reduced gray matter in frontal control networks. Methods: High-resolution T1-weighted structural MRI of 129 adolescents with BPD (aged 12-17) and 107 age-, gender-, and education-matched healthy controls (HCs) were analyzed using SBM to identify networks of covarying gray matter concentration (GMC). Borderline symptomatology, difficulties in emotion regulation, anxiety-related problems, and global functioning were assessed to characterize the meaning of neural findings. Results: Compared to HCs, adolescents with BPD exhibited significantly increased GMC in regions overlapping with the posterior hub of the DMN, and the cerebellum, and reduced GMC in frontal control regions. Importantly, the GMC alterations inside the cerebellum and the DMN positively correlated with the difficulties in emotion regulation such as emotional clarity and emotion regulation difficulties, self-harm injuries, anxiety and depressive symptoms, and negatively correlated with global assessment functioning. The deep learning model confirmed these findings and provided a good generalization performance. Conclusions: Our findings suggest that gray matter alterations in regions ascribed to the default mode network, cerebellum, and frontal control regions play a crucial role in emotional regulation deficits and self-injurious behaviors in adolescent BPD. This study provides new insights into the neurobiological mechanisms of BPD in youth and offering potential biomarker and targets for treatments.