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Peer-reviewed articleOpen access

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

Gerrans P, Mcgovern H, Hohwy J, Oestreich LKLiD

European journal of psychotraumatologyMar 19, 2026License: open accessAustralia0 citationsDOI: 10.1080/20008066.2026.2631358

Abstract

<b>Background</b>: 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.<b>Objective</b>: 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.<b>Method</b>: 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.<b>Results</b>: 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.<b>Conclusions</b>: 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.

Topics & conditions

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MDMAPTSD

Keywords

Active Inference3,4-MethylenedioxymethamphetamineMdma-assisted PsychotherapyC-ptsdComplex Post-traumatic Stress DisorderTrastorno Por Estrés Postraumático ComplejoSelf-modelling4-MetilendioximetanfetaminaAutomodeladoInferencia ActivaPsicoterapia Asistida Con MdmaTept-C

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