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

**Authors:** Philip Gerrans, Hugh Mcgovern, Jakob Hohwy, Lena K. L. Oestreich

PMC · DOI: 10.1080/20008066.2026.2631358 · 2026-03-19

## TL;DR

This paper proposes a new neurocognitive model for complex PTSD, focusing on how the brain processes emotions and self-identity, and suggests that MDMA-assisted therapy could help treat it.

## Contribution

The paper introduces a novel neurocognitive framework for C-PTSD based on predictive processing and insula function, and explores how MDMA-assisted therapy may recalibrate self-referential and emotional processes.

## Key findings

- The insula is central to emotional awareness and self-referential processing in C-PTSD.
- MDMA-assisted therapy may transiently modulate affective salience and self-referential cognition.
- Disturbances in self-organization in C-PTSD arise from maladaptive predictive regulation.

## 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.

Complex post-traumatic stress disorder (C-PTSD) arises from prolonged and/or severe trauma and is marked by difficulties with self-identity, emotional regulation, and interpersonal relationships.Our proposed model is based in active inference and highlights the insula, a key brain region for emotional awareness, as central to understanding how C-PTSD disrupts the sense of self.We propose that MDMA-assisted therapy may help rebuild a stable sense of self and improve emotional regulation, offering new hope where traditional treatments fall short.

Complex post-traumatic stress disorder (C-PTSD) arises from prolonged and/or severe trauma and is marked by difficulties with self-identity, emotional regulation, and interpersonal relationships.

Our proposed model is based in active inference and highlights the insula, a key brain region for emotional awareness, as central to understanding how C-PTSD disrupts the sense of self.

We propose that MDMA-assisted therapy may help rebuild a stable sense of self and improve emotional regulation, offering new hope where traditional treatments fall short.

## Linked entities

- **Chemicals:** 3,4-methylenedioxymethamphetamine (PubChem CID 1615), MDMA (PubChem CID 1615)
- **Diseases:** post-traumatic stress disorder (MONDO:0005146), PTSD (MONDO:0005146)

## Full-text entities

- **Genes:** OXT (oxytocin/neurophysin I prepropeptide) [NCBI Gene 5020] {aka OT, OT-NPI, OXT-NPI}, HTR2A (5-hydroxytryptamine receptor 2A) [NCBI Gene 3356] {aka 5-HT2A, HTR2}
- **Diseases:** trauma (MESH:D014947), impaired interpersonal trust (MESH:D060825), affective dysregulation (MESH:D021081), borderline personality disorder (MESH:D001883), abuse (MESH:D019966), DSO (MESH:D000092124), neurocognitive disturbances (MESH:D019965), distress (MESH:D012128), Dissociation (MESH:D004213), PTSD (MESH:D013313), disturbances in self (MESH:D012652), impaired social cognition (OMIM:300082)
- **Chemicals:** psilocybin (MESH:D011562), monoamine (-), norepinephrine (MESH:D009638), serotonin (MESH:D012701), 3,4-methylenedioxymethamphetamine (MESH:D018817), dopamine (MESH:D004298), LSD (MESH:D008238)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13003871/full.md

---
Source: https://tomesphere.com/paper/PMC13003871