The impact of early adversity on the cerebral cortex - a Mendelian randomization study

Zhen Wang; Jing Zou; Le Zhang; Jinghua Ning; Xin Zhang; Bei Jiang; Yi Liang; Yuzhe Zhang

doi:10.3389/fnins.2023.1283159

The impact of early adversity on the cerebral cortex - a Mendelian randomization study

Front Neurosci. 2023 Oct 27:17:1283159. doi: 10.3389/fnins.2023.1283159. eCollection 2023.

Authors

Zhen Wang¹, Jing Zou², Le Zhang¹, Jinghua Ning¹, Xin Zhang¹, Bei Jiang³, Yi Liang⁴, Yuzhe Zhang¹

Affiliations

¹ College of Basic Medical Sciences, Dali University, Dali, Yunnan, China.
² The First Affiliated Hospital of Dali University, Dali, Yunnan, China.
³ Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan (Cultivation), Dali, Yunnan, China.
⁴ Princess Margaret Cancer Centre, University Health Network, TMDT-MaRS Centre, Toronto, ON, Canada.

Abstract

Background: The early adversity is associated with a series of negative outcomes in adulthood, and the impact on the cerebral cortex may be one of the fundamental causes of these adverse consequences in adulthood. In this study, we aim to investigate the causal relationship between early adversity and changes in cerebral cortex structure using Mendelian randomization (MR) analysis.

Methods: The GWAS summary statistics of 6 early adversity traits were obtained from individuals of European ancestry in the UK Biobank. The GWAS summary statistics of 34 known functional cortical regions were obtained from the ENIGMA Consortium. Causal relationships between the adversity factors and brain cortical structure were assessed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods, with IVW being the primary evaluation method. Cochran's Q-test, MR-PRESSO, leave-one-out analysis, and funnel plot examination were employed to detect potential heterogeneity and pleiotropy, as well as to identify and exclude outliers.

Results: At a global level, no causal relationship was found between early adversity and cortical thickness (TH) or surface area (SA) of the brain. However, at the regional level, early adversity was found to potentially influence the TH of the caudal anterior cingulate, superior temporal, entorhinal, paracentral, lateral occipital, banks of the superior temporal sulcus, and supramarginal regions, as well as the SA of the pars triangularis, lateral occipital, parahippocampal, medial orbitofrontal, and isthmus cingulate regions. All findings were nominally significant and passed sensitivity analyses, with no significant heterogeneity or pleiotropy detected.

Discussion: Our study provides evidence for the association between early adversity and alterations in brain cortical structure, which may serve as a foundation for certain mental disorders. Furthermore, magnetic resonance imaging (MRI) might be considered as a promising tool to aid healthcare professionals in identifying individuals with a history of adverse experiences, allowing for early interventions.

Keywords: Mendelian randomization (MR); brain structure; cerebral cortex; early adversity; lateral occipital cortex.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by General Project of the Joint Special Project of Local Universities in Yunnan Province (202001BA070001-064, 202101BA070001-102), Dali University Doctoral Research Start-up Fund Project (KYBS2018012), Yunnan Provincial Department of Education Scientific Research Fund Project (2023Y0950, 2022Y80) and Open Project of Key Laboratory of Screening and Research of Resistant Plant Resources in West Yunnan, Yunnan Province (APKL2101).