Bridging Brain and Mind: A Transdiagnostic Review of Anguish, Anxiety, and Depression

Background Anguish, anxiety, and depression rank among the most disabling mental health conditions worldwide. Frequently co-occurring, they form a complex constellation of affective, cognitive, and physiological disturbances that blur traditional diagnostic boundaries. Although substantial progress has been made in elucidating their biological and psychological underpinnings, the dynamic interplay between these dimensions remains incompletely understood. This review synthesizes recent evidence on the neurological and psychological dimensions of anguish, anxiety, and depression, with the goal of identifying shared mechanisms and disorder-specific features. Methods A systematic search was conducted in PubMed, PsycINFO, Scopus, Web of Science, and SpringerLink for studies published between 2013 and 2023. Eligible articles examined neurological or psychological correlates of these conditions in adult populations. The review adhered to PRISMA 2020 guidelines. Results From an initial pool of 3,245 studies, 87 met all inclusion criteria. Neurological findings converged on disruptions within cortico-limbic circuits, altered hypothalamic–pituitary–adrenal (HPA) axis activity, and imbalances in monoaminergic and glutamatergic signaling. Psychologically, the most consistent patterns included maladaptive cognitive schemas, deficits in emotion regulation, and pervasive negative affectivity. Although less frequently investigated, anguish exhibited neuropsychological overlaps with both anxiety and depression, particularly in regions governing interoceptive awareness and self-referential processing. Conclusion Anguish, anxiety, and depression share a neuropsychological architecture that transcends categorical diagnoses. Integrating biological and psychological perspectives within a transdiagnostic framework may yield more precise models of mental suffering and foster interventions that address its shared mechanisms rather than its surface manifestations.