Interaction of negative valence system and cognitive system

High levels of trait anger and aggressive behavior are common and problematic phenomena in patients with borderline personality disorder (BPD). In BPD, patterns of reactive aggression often lead to functional impairment affecting important areas of life. Despite the high burden on individuals and their social environment, there are no specific, cost-effective treatments to reduce aggression in BPD. In previous studies, we and others have been able to infer specific biobehavioral mechanisms underlying patterns of reactive aggression in BPD that can be used as potential treatment targets. To address this, we developed a mechanism-based anti-aggression psychotherapy (MAAP) for the group setting that specifically targets the biobehavioral mechanisms underlying outward-directed aggression in BPD. A previously conducted proof-of-concept study had suggested beneficial effects for this neglected group of patients. In this multicenter, confirmatory, randomized-controlled-clinical-trial, MAAP, which consists of multifaceted, evidence-based treatment elements adapted from other sophisticated treatment programs such as Dialectical Behavior Therapy and Mentalization-Based Treatment, is tested for efficacy against a non-specific supportive psychotherapy (NSSP) program focusing on non-specific general factors of psychotherapy at seven different sites in Germany. Both treatment arms, based on one individual and 13 group therapeutic sessions (1.5 h per session, twice a week), are delivered over a period of 7–10 weeks. A total of N = 186 patients will be recruited, half of whom will be cluster-randomized to MAAP. Outcomes are assessed at baseline, immediately, and 4, 12, 20, and 24 weeks post-treatment using ecological momentary assessment, clinical interviews, questionnaires, and online tasks. If proven superior, MAAP can be incorporated into standard psychiatric care, filling a critical gap in the current therapeutic landscape by offering a structured, cost-effective, and evidence-based treatment that directly targets the biobehavioral mechanisms underlying reactive aggression in BPD. By potentially improving clinical outcomes and reducing the burden of reactive aggression in BPD, MAAP could be beneficial for both individuals and their social environments. The study’s large, multicenter design enhances the generalizability of the results, making them more relevant for broader clinical applications.

Early life stress is associated with alterations in brain function and connectivity during affective processing, especially in the fronto-limbic pathway. However, most of the previous studies were limited to a small set of priori-selected regions and did not address the impact of stress timing on functional connectivity. Using data from a longitudinal birth cohort study (n = 161, 87 females, mean age (SD) = 32.2(0.3)), we investigated the associations between different time points of stress exposure and functional connectivity. We measured stressful life events across development using a modified version of Munich Event List and grouped into four developmental stages: prenatal/newborn (prenatal-3 months), infancy and toddlerhood (3 months-4.5 years), childhood (4.5–11 years), and adolescence (11–19 years). All participants completed an fMRI-based emotion regulation task at the age of 33 years. Task-dependent directed functional connectivity was calculated using whole-brain generalized psychophysiological interactions. The association between life stress and connectivity was investigated within a multiple regression framework. Our findings revealed distinct associations between stress exposure and task-specific functional connectivity, depending on the developmental timing of stress exposure. While prenatal and childhood stress were associated with lower connectivity between subcortex and cognitive networks, stress exposure unique to adolescence was related to higher connectivity from the salience network to the cognitive networks. These results suggest that early life stress alters the connectivity of cognitive and limbic networks, which are important for emotion processing and regulation. Future research should replicate and extend the findings regarding sensitive periods by utilizing diverse paradigms in cognitive, social, and emotional domains.