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Abnormalities in brain structure following childhood unpredictability: a mechanism underlying depressive and anxiety symptoms

Published online by Cambridge University Press:  02 June 2023

Zhengxinyue Wang
Center for Cognition and Brain Disorders of Affiliated Hospital, Hangzhou Normal University, Hangzhou, China Center for Early Environment and Brain Development, School of Education, Guangzhou University, Guangzhou, China
Xinyu Cao
Center for Cognition and Brain Disorders of Affiliated Hospital, Hangzhou Normal University, Hangzhou, China Center for Early Environment and Brain Development, School of Education, Guangzhou University, Guangzhou, China
Xiaoyu Zheng
Center for Cognition and Brain Disorders of Affiliated Hospital, Hangzhou Normal University, Hangzhou, China Center for Early Environment and Brain Development, School of Education, Guangzhou University, Guangzhou, China
Yuanyuan Chen*
Center for Early Environment and Brain Development, School of Education, Guangzhou University, Guangzhou, China Department of Psychology, Guangzhou University, Guangzhou, China
Jianjun Zhu*
Center for Early Environment and Brain Development, School of Education, Guangzhou University, Guangzhou, China Department of Psychology, Guangzhou University, Guangzhou, China
Corresponding author: Jianjun Zhu; Email: Co-corresponding author: Yuanyuan Chen; Email:
Corresponding author: Jianjun Zhu; Email: Co-corresponding author: Yuanyuan Chen; Email:



Childhood adversity is associated with abnormalities in brain structure, but this association has not been tested for childhood unpredictability, one form of adversity. We studied whether abnormalities in gray matter volume (GMV) could be a mechanism linking childhood unpredictability and psychopathology, over and above the effect of childhood trauma.


Participants were 158 right-handed healthy young adults (aged 17–28 years, M = 22.07, s.d. = 2.08; 66.46% female) who underwent structural magnetic resonance imaging measurements and provided retrospective reports of childhood unpredictability. The anxiety and depression subscales of the self-report Brief Symptom Inventory-53 were used to index psychopathology.


Whole-brain voxel-based morphometric analyses showed that after controlling for the effect of childhood trauma, childhood unpredictability was correlated with greater GMV in bilateral frontal pole, bilateral precuneus, bilateral postcentral gyrus, right hemisphere of fusiform, and lingual gyrus, and left hemisphere of ventrolateral prefrontal cortex as well as occipital gyrus. Greater GMV in bilateral frontal pole, bilateral precuneus, and bilateral postcentral gyrus mediated associations between unpredictability and symptoms of depression and anxiety.


The findings suggest that childhood unpredictability could exact unique effects on neural development, over and above the effect of childhood trauma. These findings are relevant for understanding the occurrence of psychopathology following childhood unpredictability and have implications for intervention.

Original Article
Copyright © The Author(s), 2023. Published by Cambridge University Press

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These authors contributed equally to this work.


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