Network-Pluralistic Psychiatry in Epilepsy: A theoretical framework and research agenda for personalized,...

Psychiatric comorbidities in epilepsy are prevalent, disabling, and persistently undertreated due to conceptual and operational fragmentation between neurology and psychiatry. This paper proposes Network-Pluralistic Psychiatry in Epilepsy (NPPE), a hypothesis-generating, disease-contextualized framework that integrates four mechanistic layers: (1) shared genetic vulnerability, (2) epileptogenic network dysfunction as a neuropsychiatric substrate, (3) a bidirectional psychosocial stress loop, and (4) societal and institutional amplifiers. NPPE moves beyond high-level biopsychosocial heuristics by positing testable causal pathways linking genetic liability to network instability, symptom expression, and environmental feedback in epilepsy. The manuscript situates NPPE within existing integrated-care paradigms (e.g., collaborative and stepped-care models), proposing NPPE as a mechanistic engine to personalize measurement-based treatment-to-target decisions while explicitly acknowledging feasibility constraints for advanced tools. A tiered assessment concept (Tiers 1-3) and candidate mechanism-informed interventions are outlined as research targets rather than clinical recommendations. The paper delineates a research agenda prioritizing longitudinal, multimodal cohorts; incorporation of network biomarkers in clinical trials; evaluation of integrated-care implementations; and attention to equity and real-world feasibility. NPPE aims to provide a coherent, testable roadmap to transform descriptive comorbidity accounts into mechanism-oriented, personalized neuropsychiatric care in epilepsy, contingent on rigorous validation, refinement, or falsification.