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Do brain regions involved in threat processing mediate the association between developmental trauma and psychosis

Jung, P.G.Y., Mason, A., Merritt, K., McCrory, E., Roiser, J.P., Jones, D.K., Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211, David, A.S. and Bloomfield, M.A.P. 2023. Do brain regions involved in threat processing mediate the association between developmental trauma and psychosis. Neuroscience Applied 2 10.1016/j.nsa.2023.101069

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License Start date: 4 February 2023

Abstract

Background: There is growing evidence that developmental trauma - psychologically traumatic events during childhood and/or adolescence – is causally associated with increased risk of psychosis in adulthood [1]. However, an understanding of the precise mechanisms underlying this is lacking. Consistent with biopsychosocial and computational theories of psychosis [2,3], multiple lines of evidence converge on the role of altered threat processing in the pathway linking developmental trauma and psychosis [4,5]. Here, in a well-characterised birth cohort, we investigate prospectively, the effect of developmental trauma on volumes of brain structures involved in threat processing, and examine their roles in the association between developmental trauma and psychotic experiences in adulthood. Methods: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) study, a large population-based cohort in the United Kingdom. Data from 418 participants were derived from parent- or self-reported assessments. Trauma variables represent trauma exposure (between 0-17 years), the number of types, and timing of trauma: childhood (0-10.9 years) or adolescence (11-17 years). Psychotic experiences were assessed using the psychosis-like symptoms semi-structured interview at 12 and 18 years. Magnetic resonance imaging was used to measure volumes of the whole brain, amygdala, vmPFC, and striatum at age 18. We used logistic and linear regression, and mediation analyses to examine associations. In addition, we explored whether these associations could be explained by genetic confounding or reverse causation, by repeating analyses (1) whilst adjusting for schizophrenia polygenic risk scores (PRS), and (2) in a subgroup of individuals who did not report psychotic experiences at age 12 (n=304). Results: Exposure to developmental trauma was associated with an increased odds of psychotic experiences at age 18 (OR=1.80; 95% CI=1.17-2.81, p<.001), with evidence supporting dose-response effects for exposure to multiple trauma types (B=.18, p<.001, R2=.05), and at both age periods (B=.15, p<.001, R2=.03). Developmental trauma was associated with reduced left amygdalar volumes in adulthood (B=-.01, p<.01, R2=.02), with evidence supporting a dose-response association, whereby exposure to three or more types of trauma (B=-.004, p<.05, R2=.01), and exposure to trauma during both childhood and adolescence (B=-.003, p<.05, R2=.01), had a greater effect compared with exposure during childhood or adolescence only. Developmental trauma was not associated with alterations in vmPFC and striatal volumes. Reduced left amygdalar volumes mediated 16% (95% CI=2%-80%, p=.03) of the association between developmental trauma and psychotic experiences (mediation effect: 0.04, 95% CI=0.01-0.08, p=.015). These findings substantively remained the same in sensitivity analyses aimed to minimise the effects of reverse causation and genetic confounding. Conclusions: In this study, we found evidence of a dose-response association between developmental trauma and reduced left amygdalar volumes in adulthood, and of a mediating role of left amygdalar volumes in the trauma-psychosis association. These findings were not explained by reverse causation or genetic confounding. These findings provide observational evidence for the hypothesis that a causal association between developmental trauma and altered threat processing underlies vulnerability to psychosis. Importantly, our identification of a neurobiological mediator of the trauma-psychosis relationship informs strategies for secondary and tertiary prevention of psychosis associated with developmental trauma.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2023-02-04
Publisher: Elsevier
ISSN: 2772-4085
Date of First Compliant Deposit: 20 March 2023
Last Modified: 04 May 2023 16:16
URI: https://orca.cardiff.ac.uk/id/eprint/157816

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