A neurocognitive account of complex PTSD: self-modelling, affective dysregulation, and implications for MDMA-assisted and targeted psychotherapies

Background: Complex post-traumatic stress disorder (C-PTSD) is a trauma-related condition characterized by pervasive disturbances in affect regulation, self-concept, and interpersonal functioning that extend beyond the symptom profile of post-traumatic stress disorder (PTSD). While neurobiological studies have implicated limbic, salience, and prefrontal systems in C-PTSD, mechanistic accounts linking these findings to disturbances in self-organization and treatment-relevant processes remain underdeveloped. Objective: This narrative review develops a hypothesis-generating neurocognitive account of C-PTSD grounded in predictive processing and self-modelling frameworks, with particular emphasis on affective dysregulation and disturbances in self-organization. Method: We synthesize clinical, neurobiological, and theoretical evidence to conceptualize PTSD and C-PTSD along a continuum of regulatory stability, and to advance a conceptual model highlighting the role of insula-mediated self-modelling processes. Within this framework, we examine 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy, as one illustrative intervention that may transiently modulate affective salience, interpersonal trust, and self-referential cognition. Results: The proposed model integrates converging evidence linking insular function to interoception, affective experience, salience processing, and self-referential cognition, and situates disturbances in self-organization as emerging from maladaptive predictive regulation under conditions of prolonged interpersonal adversity. This framework helps reconcile overlapping neurobiological findings across PTSD and C-PTSD while accounting for differences in symptom generalization, relational threat processing, and affective stability. Conclusions: This review delineates a set of testable, mechanistically grounded hypotheses concerning the role of self-modelling processes in C-PTSD. These hypotheses generate specific predictions for future empirical work and inform the design and evaluation of pharmacological and psychotherapeutic interventions that aim to recalibrate affective regulation and self-referential processing in complex trauma presentations.