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

Abstract

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.

Molecular and micro-architectural mapping of gray matter alterations in psychosis

“…1b). Individuals who reported operationally-defined psychotic experiences (PEs), whether rated as ‘suspected’ ( PE-suspected , n = 48), ‘definite’ ( PE-definite , n = 73), or ‘clinical’ for those who had experienced additional signs of social impairment or help-seeking ( PE-clinical , n = 36), collectively formed the PE group 31,32 . Individuals who experienced a First Episode of Psychosis (FEP, n = 352) composed the FEP group.…”

Exploring causal mechanisms of psychosis risk

“…A number of pre and perinatal complications have a small yet robust association with an increased risk of developing psychosis ( Davies et al, 2020 ). Exposure to pre- and perinatal risk factors are associated with altered grey matter volume, with recent MRI studies highlighting enlarged striatal and reduced cingulate volumes ( Holz et al, 2023b , Merritt et al, 2023a ). As these regions (cingulate, insula, and striatum) contribute to salience processing, alterations in this network could increase an individual’s propensity to develop a psychotic disorder ( Del Fabro et al, 2021 , Palaniyappan and Liddle, 2012 ).…”

“…Adults with a history of childhood trauma display reduced grey matter in frontal and limbic networks (Calem et al, 2017; Frodl et al, 2017; Lim et al, 2014b; Paquola et al, 2016; Pollak et al, 2022; Tymofiyeva et al, 2022; Yang et al, 2023), a pattern which is also observed in psychosis patients ( Kim et al, 2015 , Picó-Pérez et al, 2022 , Shepherd et al, 2012 , van Erp et al, 2018 ). Additionally, there is some evidence of increased basal ganglia volume, which may be relevant to psychosis ( Holz et al, 2023b , Merritt et al, 2023a , Popovic et al, 2020 ). These neurodevelopmental abnormalities can increase the sensitivity of the dopaminergic system, particularly in response to stress ( Egerton et al, 2017 , Egerton et al, 2016 ).…”