• Felitti, V. J. et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. Am. J. Prev. Med. 14, 245–258 (1998).

    Article 
    PubMed 

    Google Scholar
     

  • Hughes, K. et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health 2, e356–e366 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Peterson, C. et al. Economic burden of health conditions associated with adverse childhood experiences among US adults. JAMA Netw. Open 6, e2346323 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sheridan, M. A. & McLaughlin, K. A. Dimensions of early experience and neural development: deprivation and threat. Trends Cogn. Sci. 18, 580–585 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Garner, A. S. & Shonkoff, J. P. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health. Pediatrics 129, e224–e231 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Tottenham, N. & Sheridan, M. A. A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing. Front. Hum. Neurosci. 3, 68 (2009).

    PubMed 

    Google Scholar
     

  • Smith, K. E. & Pollak, S. D. Early life stress and development: potential mechanisms for adverse outcomes. J. Neurodev. Disord. 12, 34 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jeung, J. et al. A caregiver-child intervention for mitigating toxic stress (‘the resiliency clinic’): a pilot study. Matern. Child Health J. 26, 1959–1966 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luby, J. L., Baram, T. Z., Rogers, C. E. & Barch, D. M. Neurodevelopmental optimization after early-life adversity: cross-species studies to elucidate sensitive periods and brain mechanisms to inform early intervention. Trends Neurosci. 43, 744–751 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Slopen, N., McLaughlin, K. A. & Shonkoff, J. P. Interventions to improve cortisol regulation in children: a systematic review. Pediatrics 133, 312–326 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Purewal Boparai, S. K. et al. Ameliorating the biological impacts of childhood adversity: a review of intervention programs. Child Abuse Negl. 81, 82–105 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Gilgoff, R., Singh, L., Koita, K., Gentile, B. & Marques, S. S. Adverse childhood experiences, outcomes, and interventions. Pediatr. Clin. North Am. 67, 259–273 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Campbell, T. S., Donoghue, K. M., Ghosh, U., Nelson, C. M. & Roth, T. L. Early life stress affects bdnf regulation: a role for exercise interventions. Int. J. Mol. Sci. 23, 11729 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cohen, Z. P. et al. The effect of a mindfulness-based stress intervention on neurobiological and symptom measures in adolescents with early life stress: a randomized feasibility study. BMC Complement. Med. Ther. 21, 123 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Slomine, B. S. & Copeland-Linder, N. Early-life adversity and executive functioning-highlighting an urgent need for identification, prevention, and intervention in childhood. JAMA Pediatr. 175, e212517 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Underwood, E. California Has Begun Screening for Early Childhood Trauma, but Critics Urge Caution (American Association for the Advancement of Science, 2020).

  • Baldwin, J. R. et al. Population vs individual prediction of poor health from results of adverse childhood experiences screening. JAMA Pediatr. 175, 385–393 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Meehan, A. J., Baldwin, J. R., Lewis, S. J., MacLeod, J. G. & Danese, A. Poor individual risk classification from adverse childhood experiences screening. Am. J. Prev. Med. 62, 427–432 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Anda, R. F., Porter, L. E. & Brown, D. W. Inside the Adverse Childhood Experience score: strengths, limitations, and misapplications. Am. J. Prev. Med. 59, 293–295 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • McLennan, J. D., Gonzalez, A., MacMillan, H. L. & Afifi, T. O. Routine screening for adverse childhood experiences (ACEs) still doesn’t make sense. Child Abuse Negl. https://doi.org/10.1016/j.chiabu.2024.106708 (2024).

  • Birnie, M. T. & Baram, T. Z. The evolving neurobiology of early-life stress. Neuron 113, 1474–1490 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Demaestri, C. et al. Resource scarcity but not maternal separation provokes unpredictable maternal care sequences in mice and both upregulate Crh-associated gene expression in the amygdala. Neurobiol. Stress 20, 100484 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Molet, J. et al. Fragmentation and high entropy of neonatal experience predict adolescent emotional outcome. Transl Psychiatry 6, e702 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kooiker, C. L., Chen, Y., Birnie, M. T. & Baram, T. Z. Genetic tagging uncovers a robust, selective activation of the thalamic paraventricular nucleus by adverse experiences early in life. Biol. Psychiatry Glob. Open Sci. https://doi.org/10.1016/j.bpsgos.2023.01.002 (2023).

  • Birnie, M. T. & Baram, T. Z. Principles of emotional brain circuit maturation. Science 376, 1055–1056 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, E. P. et al. Exposure to unpredictable maternal sensory signals influences cognitive development across species. Proc. Natl Acad. Sci. USA 114, 10390–10395 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, E. P. et al. Early life exposure to unpredictable parental sensory signals shapes cognitive development across three species. Front. Behav. Neurosci. 16, 960262 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, E. P. et al. Across continents and demographics, unpredictable maternal signals are associated with children’s cognitive function. EBioMedicine 46, 256–263 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, Y., Harms, M. B., Green, C. S., Wilson, R. C. & Pollak, S. D. Childhood unpredictability and the development of exploration. Proc. Natl Acad. Sci. USA 120, e2303869120 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Furtado, E. J., Camacho, M. C., Chin, J. H. & Barch, D. M. Complex emotion processing and early life adversity in the Healthy Brain Network sample. Dev. Cogn. Neurosci. 70, 101469 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Howland, M. A. et al. Prenatal maternal mood entropy is associated with child neurodevelopment. Emotion 21, 489–498 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Short, A. K. et al. Individual longitudinal changes in DNA-methylome identify signatures of early-life adversity and correlate with later outcome. Neurobiol. Stress 31, 100652 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, E. P. & Glynn, L. M. Annual Research Review: the power of predictability—patterns of signals in early life shape neurodevelopment and mental health trajectories. J. Child Psychol. Psychiatry 65, 508–534 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Spadoni, A. D. et al. Contribution of early-life unpredictability to neuropsychiatric symptom patterns in adulthood. Depress. Anxiety 39, 706–717 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hunt, C. et al. Childhood unpredictability is associated with increased risk for long- and short-term depression and anhedonia symptoms following combat deployment. J. Mood Anxiety Disord. 6, 100045 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Gillespie, M. L. & Rao, U. Relationships between depression and executive functioning in adolescents: the moderating role of unpredictable home environment. J. Child Fam. Stud. 31, 2518–2534 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mittal, C., Griskevicius, V., Simpson, J. A., Sung, S. & Young, E. S. Cognitive adaptations to stressful environments: When childhood adversity enhances adult executive function. J. Pers. Soc. Psychol. 109, 604–621 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Glynn, L. M. et al. Prenatal maternal mood patterns predict child temperament and adolescent mental health. J. Affect. Disord. 228, 83–90 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Golden, C. V. et al. Age, adverse childhood experiences, and health care utilization. Pediatrics https://doi.org/10.1542/peds.2023-064838 (2024).

  • Lindert, N. G. et al. Exposure to unpredictability and mental health: validation of the brief version of the Questionnaire of Unpredictability in Childhood (QUIC-5) in English and Spanish. Front. Psychol. 13, 971350 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Child population, by race/ethnicity 2024. KidsData https://kidsdata.org/topic/33/child-population-race/Pie#fmt=144&loc=2&tf=141&ch=7,11,70,10,72,9,73&pdist=73 (2024).

  • Oh, D. L. et al. Systematic review of pediatric health outcomes associated with childhood adversity. BMC Pediatr. 18, 83 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hart, E. R. et al. Mothers with low incomes view both individual and structural interventions as potentially helpful for supporting early child development. Sci. Rep. 14, 18374 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reemst, K. et al. Molecular underpinnings of programming by early-life stress and the protective effects of early dietary omega6/omega3 ratio, basally and in response to LPS: integrated mRNA-miRNAs approach. Brain Behav. Immun. 117, 283–297 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Mindell, J. A., Li, A. M., Sadeh, A., Kwon, R. & Goh, D. Y. Bedtime routines for young children: a dose-dependent association with sleep outcomes. Sleep 38, 717–722 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Troller-Renfree, S. V. et al. The impact of a poverty reduction intervention on infant brain activity. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2115649119 (2022).

  • Jonkman, C. S. et al. Effects of Multidimensional Treatment Foster Care for Preschoolers (MTFC-P) for young foster children with severe behavioral disturbances. J. Child Fam. Stud. 26, 1491–1503 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Houtepen, L. C. et al. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nat. Commun. 7, 10967 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • de Mendonca Filho, E. J. et al. Stress JPBRNoT. Linking specific biological signatures to different childhood adversities: findings from the HERO project. Pediatr. Res. 94, 564–574 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McLaughlin, K. A. et al. Causal effects of the early caregiving environment on development of stress response systems in children. Proc. Natl Acad. Sci. USA 112, 5637–5642 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ouellet-Morin, I. et al. Blunted cortisol responses to stress signal social and behavioral problems among maltreated/bullied 12-year-old children. Biol. Psychiatry 70, 1016–1023 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hunter, A. L., Minnis, H. & Wilson, P. Altered stress responses in children exposed to early adversity: a systematic review of salivary cortisol studies. Stress 14, 614–626 (2011).

    Article 
    PubMed 

    Google Scholar
     

  • Brotman, L. M. et al. Effects of a psychosocial family-based preventive intervention on cortisol response to a social challenge in preschoolers at high risk for antisocial behavior. Arch. Gen. Psychiatry 64, 1172–1179 (2007).

    Article 
    PubMed 

    Google Scholar
     

  • Glynn, L. M., Liu, S. R., Lucas, C. T. & Davis, E. P. Leveraging the science of early life predictability to inform policies promoting child health. Dev. Cogn. Neurosci. 69, 101437 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Glynn, L. M., Davis, E. P., Luby, J. L., Baram, T. Z. & Sandman, C. A. A predictable home environment may protect child mental health during the COVID-19 pandemic. Neurobiol. Stress 14, 100291 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Betancourt, T. S., Meyers-Ohki, S. E., Charrow, A. & Hansen, N. Annual Research Review: mental health and resilience in HIV/AIDS-affected children—a review of the literature and recommendations for future research. J. Child Psychol. Psychiatry 54, 423–444 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Crespo, C. et al. Family routines and rituals in the context of chronic conditions: a review. Int. J. Psychol. 48, 729–746 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Guidubaldi, J., Cleminshaw, H. K., Perry, J. D., Nastasi, B. K. & Lightel, J. The role of selected family environment factors in children’s post-divorce adjustment. Fam. Relat. 35, 141–151 (1986).

    Article 

    Google Scholar
     

  • Harhen, N. C. & Bornstein, A. M. Interval timing as a computational pathway from early life adversity to affective disorders. Top. Cogn. Sci. 16, 92–112 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Hardy, M. & Baram, T. Z. The importance of predictability in the early-life environment for neurodevelopment and mental health. Annu. Rev. Dev. Psychol. (in the press).

  • VanTieghem, M. et al. Longitudinal changes in amygdala, hippocampus and cortisol development following early caregiving adversity. Dev. Cogn. Neurosci. 48, 100916 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gee, D. G. et al. Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proc. Natl Acad. Sci. USA 110, 15638–15643 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Teicher, M. H., Samson, J. A., Anderson, C. M. & Ohashi, K. The effects of childhood maltreatment on brain structure, function and connectivity. Nat. Rev. Neurosci. 17, 652–666 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Barch, D. et al. Effect of hippocampal and amygdala connectivity on the relationship between preschool poverty and school-age depression. Am. J. Psychiatry 173, 625–634 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sisk, L. M. et al. Multivariate links between the developmental timing of adversity exposure and white matter tract connectivity in adulthood. Biol. Psychiatry Cogn. Neurosci. Neuroimaging https://doi.org/10.1016/j.bpsc.2025.02.003 (2025).

  • Granger, S. J. et al. Aberrant maturation of the uncinate fasciculus follows exposure to unpredictable patterns of maternal signals. J. Neurosci. 41, 1242–1250 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Davis, E. P. et al. Sex-specific effects of early-life unpredictability on hippocampal and amygdala responses to novelty in adolescents. Biol. Psychiatry Glob. Open Sci. 5, 100561 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jirsaraie, R. J. et al. Prenatal exposure to maternal mood entropy is associated with a weakened and inflexible salience network in adolescence. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 9, 207–216 (2024).

    PubMed 

    Google Scholar
     

  • Paskett, E. et al. Multilevel interventions to address health disparities show promise in improving population health. Health Aff. 35, 1429–1434 (2016).

    Article 

    Google Scholar
     

  • Allwood, M. A., Ford, J. D. & Levendosky, A. Introduction to the special issue: disproportionate trauma, stress, and adversities as a pathway to health disparities among disenfranchised groups globally. J. Trauma Stress 34, 899–904 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Williams, D. R. Stress and the mental health of populations of color: advancing our understanding of race-related stressors. J. Health Soc. Behav. 59, 466–485 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, S. R., Kia-Keating, M., Santacrose, D. E. & Modir, S. Linking profiles of neighborhood elements to health and related outcomes among children across the United States. Health Place 53, 203–209 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • California Initiative to Advance Precision Medicine 2016 (California Health and Human Services, 2026); https://www.chhs.ca.gov/blog/2026/06/08/50505/

  • Thakur, N. et al. Pediatrics adverse childhood experiences and related life events screener (PEARLS) and health in a safety-net practice. Child Abuse Negl. 108, 104685 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Glynn, L. M. et al. Measuring novel antecedents of mental illness: the Questionnaire of Unpredictability in Childhood. Neuropsychopharmacology 44, 876–882 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Liu, S. R. et al. The QUIC-SP: a Spanish language tool assessing unpredictability in early life is linked to physical and mental health. PLoS ONE 20, e0298296 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anderson, S. E. & Whitaker, R. C. Association of self-regulation with obesity in boys vs girls in a US national sample. JAMA Pediatr. 172, 842–850 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar