Emotion Regulation and Brain Mechanisms: A Transdiagnostic Perspective on Neural Circuits, Individual Differences, and Clinical Translation

Abstract

Emotion regulation (ER) difficulties are now firmly established as a transdiagnostic feature of psychiatric and stress-related disorders. Large-scale meta-analyses published in 2026 confirmed ER impairments across fifteen diagnostic categories, shifting the key question from whether ER is transdiagnostic to how this knowledge can inform diagnosis and treatment. This Perspective argues that ER should be conceptualized as a transdiagnostic neurocognitive dimension rather than a disorder-specific deficit. To support this view, three complementary studies are integrated: neuroimaging studies of prefrontal-limbic and large-scale brain networks involved in cognitive reappraisal; evidence of ER-related neural alterations across mood, anxiety, trauma-related, personality, and addictive disorders; and research on individual differences and neuromodulation that explain variability in regulatory capacity and treatment response. ER is framed within a broader executive-function model, operating as a “hot” executive process alongside “cool” cognitive-control functions. Building on this evidence, a Layered Transdiagnostic Model of Emotion Regulation (LTM-ER) is proposed. The model includes a shared transdiagnostic core circuit (Layer 1), disorder-specific neural signatures (Layer 2), and individual moderators such as developmental history, dispositional traits, regulatory strategies, and stimulation parameters (Layer 3). Five testable predictions are derived from the model, highlighting how multimodal biomarkers and personalized interventions may advance precision approaches to emotion dysregulation across psychiatric disorders.