The impact of cumulative obstetric complications and childhood trauma on brain volume in young people with psychotic experiences

Kate Merritt, Pedro Luque Laguna, Arjun Sethi, Mark Drakesmith, Sarah A. Ashley, Michael Bloomfield, Leon Fonville, Gavin Perry, Tom Lancaster, Stavros I. Dimitriadis, Stanley Zammit, C. John Evans, Glyn Lewis, Matthew J. Kempton, David E.J. Linden, Abraham Reichenberg, Derek K. Jones, Anthony S. David

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Psychotic experiences (PEs) occur in 5–10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual’s propensity to develop later psychotic disorders.

Original languageEnglish
JournalMolecular Psychiatry
Early online date30 Oct 2023
Publication statusPublished - 30 Oct 2023

Bibliographical note

Funding Information:
The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and ASD will serve as the guarantor for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website ( ). ASD was supported by the MRC (Grant Ref MR/S003436/1), and DEL by the MRC (MR/K004360/1). DKJ was supported in part by a Wellcome Trust Investigator Award (096646/Z/11/Z) and a Wellcome Trust Strategic Award (104943/Z/14/Z). SZ is supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. SAA is supported by the Seaver Autism Centre, Mount Sinai. GL is supported by the UCLH BRC. SID is supported by a Beatriu de Pinós fellowship (2020 BP 00116). SID and DEL were supported by grant MR/K004360/1 from the Medical Research Council (MRC). For the purpose of open access, the author has applied a CC-BY public copyright licence to any author accepted manuscript version arising from this submission. We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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