Document Type
Article
Publication Date
7-7-2025
Abstract
Background
Unpredictable childhood experiences are an understudied form of early-life adversity that impact neurodevelopment. The neurobiological processes by which exposure to early-life unpredictability impact development and vulnerability to psychopathology remain poorly understood. In the current study, we investigated the sex-specific consequences of early-life unpredictability on the limbic network, focusing on the hippocampus and the amygdala.
Methods
Participants included 150 youths (54% female). Early-life unpredictability was assessed using the Questionnaire of Unpredictability in Childhood (QUIC). Participants engaged in 1 or more task–functional magnetic resonance imaging scans between the ages of 8 and 17 (223 total observations) measuring blood oxygen level–dependent (BOLD) responses to novel and familiar scenes.
Results
Exposure to early-life unpredictability was associated with BOLD contrast (novel vs. familiar) in a sex-specific manner. For boys, but not girls, higher QUIC scores were associated with lower BOLD activation in response to novel versus familiar stimuli in the hippocampal head and amygdala. Secondary psychophysiological interaction analyses revealed complementary sex-specific associations between QUIC scores and condition-specific functional connectivity between the right and left amygdala, as well as between the right amygdala and hippocampus bilaterally.
Conclusions
Exposure to unpredictability in early life has persistent implications for the functional operations of limbic circuits. Importantly, consistent with emerging experimental animal and human studies, the consequences of early-life unpredictability differ for boys and girls. Furthermore, impacts of early-life unpredictability were independent of other risk factors including lower household income and negative life events, indicating distinct consequences of early-life unpredictability beyond more commonly studied types of early-life adversity.
Recommended Citation
Davis, E. P., Leonard, B. T., Jirsaraie, R. J., Keator, D. B., Small, S. L., Sandman, C. A., Risbrough, V. B., Stern, H. S., Glynn, L. M., Yassa, M. A., Baram, T. Z., & Rasmussen, J. M. (2025). Sex-specific effects of early-life unpredictability on hippocampal and amygdala responses to novelty in adolescents. Biological Psychiatry Global Open Science, 5(6), 100561. https://doi.org/10.1016/j.bpsgos.2025.100561
Supplementary material
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Child Psychology Commons, Developmental Neuroscience Commons, Maternal and Child Health Commons, Medical Neurobiology Commons, Other Mental and Social Health Commons, Psychiatric and Mental Health Commons
Comments
This article was originally published in Biological Psychiatry Global Open Science, volume 5, issue 6, in 2025. https://doi.org/10.1016/j.bpsgos.2025.100561