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

Philip Gerrans, Hugh McGovern, Jakob Hohwy, Lena K L Oestreich

European Journal of Psychotraumatology March 19, 2026 DOI: 10.1080/20008066.2026.2631358 (opens in new tab)

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Characteristics Narrative review Peer reviewed
Topics MDMA Psychedelic-assisted therapy PTSD
Keywords 3,4-methylenedioxymethamphetamine 4-metilendioximetanfetamina C-PTSD MDMA-Assisted Psychotherapy Tept-c Active inference Automodelado Inferencia activa Self-modelling
Key findings The proposed framework integrates insula-mediated self-modelling processes to explain disturbances in self-organization in C-PTSD as emerging from maladaptive predictive regulation under prolonged interpersonal adversity.

Abstract

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.

Comparable studies

Other narrative reviews on MDMA for PTSD, most cited first.

Study Year Design Participants
Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. 2016 Review
MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? 2018 Review
Clinical applications of hallucinogens: A review. 2016 Review
MDMA‐Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta‐Analysis 2021 Review
Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... 2021 Review n = 70

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