There is heterogeneity in brain regions thought to underpin psychosis.

Some regions overlap with those associated with PTSD (e.g., insula, hippocampus).

Comorbid cPTSD is associated with neuroanatomical differences in people with psychosis.

Heterogeneity in the underpinnings of psychosis may be due to overlooked cPTSD.

Childhood maltreatment and complex post-traumatic stress disorder (cPTSD) are common among people with psychosis. Traumatic life experiences may contribute to the neural substrates of psychosis. Affective pathways to psychosis outline the role of post-traumatic sequelae, but no studies have explored the neurobiological underpinnings of cPTSD in this population. We compared two groups meeting criteria for schizophrenia-spectrum disorders, with (n = 58) and without (n = 50) comorbid cPTSD. Region of interest (ROI) analysis was used to assess structural differences in ROIs identified by meta-analyses as overlapping between PTSD and psychosis. The cPTSD group showed enlarged limbic regions, including the bilateral anterior insula and left parahippocampus, and smaller prefrontal regions, including the left medial orbitofrontal cortex (mOFC). In the right mOFC, specific voxel volumes were larger, and others smaller, in the cPTSD group. All differences, aside from hippocampal volume, survived whole-brain analysis corrected for multiple comparisons. Post-hoc analyses indicated trends suggesting bilateral insula and mOFC volume correlated positively, whereas parahippocampal volume correlated negatively, with cPTSD symptom severity. To conclude, in people with comorbid cPTSD and psychosis, post-traumatic sequelae may be underpinned by anatomical differences in regions implicated in emotion regulation, especially the regulation of fear, supporting the neural characterisation of affective psychosis pathways.

Trauma

Schizophrenia

Magnetic resonance imaging

Neuroimaging

Whole-brain analysis

Disturbances of self-organisation

© 2026 The Author(s). Published by Elsevier B.V.