ArticleBiological psychiatry global open science2025
Sex-Specific Effects of Early-Life Unpredictability on Hippocampal and Amygdala Responses to Novelty in Adolescents.
Article in Biological psychiatry global open science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- A protocol for the Teen Bugs study: An integrative, multi-omics approach to understanding the role of the gut microbiome and mesocorticolimbic system in adolescent mental health following early adverse caregiving.Brain, behavior, & immunity - health · 2026Article
- Longitudinal MRI reveals adolescent pituitary growth patterns linked to puberty and environmental exposures.medRxiv : the preprint server for health sciences · 2026Article
- Anhedonia buffers the effects of early-life unpredictability on threat-reward decision-making.bioRxiv : the preprint server for biology · 2026Article
- Unpredictability is a childhood adversity that contributes to mental health problems.Nature. Mental health · 2026Article
- The evolving neurobiology of early-life stress.Neuron · 2025Review
- Sex-Specific Associations Between Early-Life Unpredictability and Trajectories of Body Mass Index From Infancy to Adolescence.Biopsychosocial science and medicineArticle
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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.
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