Childhood adversity and adolescent stress cardiovascular dysregulation: Moderating role of autonomic nervous system multilocus genetic variation

doi:10.3724/SP.J.1041.2026.1736

Abstract

Abstract: Childhood adversity is one of the most important environmental risk factors that leads to stress cardiovascular dysregulation, which is innervated by the autonomic nervous system. However, few studies have examined the interaction effects of environmental factors and genetic polymorphisms on cardiovascular reactivity to stress among adolescents. Adopting a multilocus genetic profile score (MGPS) approach, the present study aimed to explore the associations between childhood adversity and adolescent cardiovascular reactivity to stress, and test the moderating role of the autonomic nervous system genetic polymorphisms.
Two independent samples (sample 1 included 256 adolescents, M_age=12.95 ± 0.79 years old; Sample 2 included 358 adolescents, M_age=12.98 ± 0.74 years old) were recruited from two middle schools in northwest China. Cardiovascular reactivity was induced by a speech task and a mental arithmetic task in sample 1 and sample 2, respectively.
Results showed that childhood adversity was negatively associated with cardiovascular reactivity to stress, and these associations were moderated by MGPS. Specifically, compared to adolescents with lower MGPS, those with higher MGPS exhibited lower (or blunt) cardiovascular reactivity to stress when exposed to high childhood adversity, and exhibited greater cardiovascular reactivity to stress when exposed to low childhood adversity.
Findings suggest that childhood adversity and autonomic nervous system genetic polymorphisms interactively impact stress cardiovascular function among adolescents, and have implications for interventions targeted at improving stress cardiovascular function in adolescents with childhood adversity.

Key words: childhood adversity, stress cardiovascular reactivity, autonomic nervous system, multilocus genetic profile score

HUANG Ye Fei, LÜ Wei. (2026). Childhood adversity and adolescent stress cardiovascular dysregulation: Moderating role of autonomic nervous system multilocus genetic variation. Acta Psychologica Sinica, 58(9), 1736-1750.

References

[1] Allegrini A. G., Evans B. E., de Rooij S., Greaves-Lord K., & Huizink A. C. (2019). Gene × Environment contributions to autonomic stress reactivity in youth.Development and Psychopathology, 31(1), 293-307.
[2] Apparsundaram S., Ferguson S. M., George Jr A. L., & Blakely R. D. (2000). Molecular cloning of a human, hemicholinium-3-sensitive choline transporter.Biochemical and Biophysical Research Communications, 276(3), 862-867.
[3] Bath, K. G., & Lee, F. S. (2006). Variant BDNF (Val66Met) impact on brain structure and function.Cognitive, Affective, & Behavioral Neuroscience, 6(1), 79-85.
[4] Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences.Psychological Bulletin, 135(6), 885-908.
[5] Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing.Journal of the Royal Statistical Society: Series B (Methodological), 57(1), 289-300.
[6] Bernstein D. P., Stein J. A., Newcomb M. D., Walker E., Pogge D., Ahluvalia T., … Zule W. (2003). Development and validation of a brief screening version of the Childhood Trauma Questionnaire.Child Abuse & Neglect, 27(2), 169-190.
[7] Bilo G., Zorzi C., Munera J. E. O., Torlasco C., Giuli V., & Parati G. (2015). Validation of the SOMNOtouch-NIBP noninvasive continuous blood pressure monitor according to the European Society of Hypertension International Protocol revision 2010.Blood Pressure Monitoring, 20(5), 291-294.
[8] Brindle R. C., Pearson A., & Ginty A. T. (2022). Adverse childhood experiences (ACEs) relate to blunted cardiovascular and cortisol reactivity to acute laboratory stress: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 134, 104530.
[9] Broekhof R., Nordahl H. M., Bjørnelv S., & Selvik S. G. (2022). Prevalence of adverse childhood experiences and their co-occurrence in a large population of adolescents: A young HUNT 3 study.Social Psychiatry and Psychiatric Epidemiology, 57(12), 2359-2366.
[10] Bucci M., Marques S. S., Oh D., & Harris N. B. (2016). Toxic stress in children and adolescents.Advances in Pediatrics, 63(1), 403-428.
[11] Cao, C., & Rijlaarsdam, J. (2023). Childhood parenting and adolescent internalizing and externalizing symptoms: Moderation by multilocus hypothalamic-pituitary-adrenal axis-related genetic variation.Development and Psychopathology, 35(2), 524-536.
[12] Chang C. C., Chang H. A., Chen T. Y., Fang W. H., & Huang S. Y. (2014). Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic tone in a gender-specific way. Psychoneuroendocrinology, 47, 17-25.
[13] Chang C. C., Fang W. H., Chang H. A., Chang T. C., Shyu J. F., & Huang S. Y. (2017). Serotonin 2A receptor (5-HT2A) gene promoter variant interacts with chronic perceived stress to modulate resting parasympathetic activity in humans.Psychoneuroendocrinology, 76, 119-126.
[14] Choi S. W., Mak T. S.-H., & O’Reilly P. F. (2020). Tutorial: A guide to performing polygenic risk score analyses.Nature Protocols, 15(9), 2759-2772.
[15] Chung, M. C., & Chen, Z. S. (2017). Child abuse and psychiatric co-morbidity among Chinese adolescents: Emotional processing as mediator and PTSD from past trauma as moderator.Child Psychiatry and Human Development, 48(4), 610-618.
[16] Domingue B. W., Trejo S., Armstrong-Carter E., & Tucker-Drob E. M. (2020). Interactions between polygenic scores and environments: Methodological and conceptual challenges. Sociological Science, 7, 465-486.
[17] Engel, M. L., & Gunnar, M. R. (2020). The development of stress reactivity and regulation during human development. International Review of Neurobiology, 150, 41-76.
[18] Gatt J. M., Nemeroff C. B., Dobson-Stone C., Paul R. H., Bryant R. A., Schofield P. R., .. Williams L. M. (2009). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety.Molecular Psychiatry, 14(7), 681-695.
[19] Gesche H., Grosskurth D., Küchler G., & Patzak A. (2012). Continuous blood pressure measurement by using the pulse transit time: Comparison to a cuff-based method.European Journal of Applied Physiology, 112(1), 309-315.
[20] Godoy L. C., Frankfurter C., Cooper M., Lay C., Maunder R., & Farkouh M. E. (2021). Association of adverse childhood experiences with cardiovascular disease later in life: A review. JAMA Cardiology, 6(2), 228-235.
[21] Heim C., Newport D. J., Heit S., Graham Y. P., Wilcox M., Bonsall R., .. Nemeroff C. B. (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood.JAMA: Journal of the American Medical Association, 284(5), 592-597.
[22] Jones C. W., Gray S. A., Theall K. P., & Drury S. S. (2018). Polymorphic variation in the SLC5A7 gene influences infant autonomic reactivity and self-regulation: A neurobiological model for ANS stress responsivity and infant temperament.Psychoneuroendocrinology, 97, 28-36.
[23] Juster R. P., McEwen B. S., & Lupien S. J. (2010). Allostatic load biomarkers of chronic stress and impact on health and cognition.Neuroscience and Biobehavioral Reviews, 35(1), 2-16.
[24] Keijser R., Olofsdotter S., Nilsson K. W., & Åslund C. (2021). Three-way interaction effects of early life stress, positive parenting and FKBP5 in the development of depressive symptoms in a general population.Journal of Neural Transmission, 128(9), 1409-1424.
[25] Keogh T. M., Howard S., & Gallagher S. (2022). Early life adversity and blunted cardiovascular reactivity to acute psychological stress: The role of current depressive symptoms.Psychosomatic Medicine, 84(2), 170-178.
[26] Kermorgant M., Pavy-Le Traon A., Senard J. M., & Arvanitis D. N. (2018). Serotonergic receptor 5-HT_2A in the cardiosympathovagal system.5-HT2A Receptors in the Central Nervous System, 32, 137-145.
[27] Koopman C., Carrion V., Butler L. D., Sudhakar S., Palmer L., & Steiner H. (2004). Relationships of dissociation and childhood abuse and neglect with heart rate in delinquent adolescents.Journal of Traumatic Stress, 17(1), 47-54.
[28] Lang P. J., Bradley M. M., & Cuthbert B. N. (2005). International affective picture system (IAPS): Affective ratings of pictures and instruction manual. University of Florida Center for Research in Psychophysiology, Gainesville, FL.
[29] Li-Tempel T., Larra M. F., Sandt E., Mériaux S. B., Schote A. B., Schächinger H., Muller C. P., & Turner J. D. (2016). The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation.Clinical Epigenetics, 8, 12.
[30] Llabre M. M., Spitzer S. B., Saab P. G., Ironson G. H., & Schneiderman N. (1991). The reliability and specificity of delta versus residualized change as measures of cardiovascular reactivity to behavioral challenges.Psychophysiology, 28(6), 701-711.
[31] Lü, W., & Huang, Y. (2025). Quadratic associations between cardiovascular stress reactivity and development of cool and hot executive functions in adolescents.Development and Psychopathology, 37(2), 664-677.
[32] Lü W., Ji H., & Li Y. (2023). Early life adversity and cardiovascular responses to repeated stress among adolescents: Moderating role of COMT gene rs4680 polymorphism. Psychoneuroendocrinology, 150, 106029.
[33] McEwen, B. S., & Wingfield, J. C. (2003). The concept of allostasis in biology and biomedicine.Hormones and Behavior, 43(1), 2-15.
[34] McKenna B. G., Hammen C., & Brennan P. A. (2021). HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood.Development and Psychopathology, 33(1), 122-134.
[35] McLaughlin, K. A. (2016). Future directions in childhood adversity and youth psychopathology.Journal of Clinical Child and Adolescent Psychology, 45(3), 361-382.
[36] Miao J., Wu Y., & Lu Q. (2024). Statistical methods for gene-environment interaction analysis.Wiley interdisciplinary reviews. Computational Statistics, 16(1), e1635.
[37] Monroe, S. M., & Simons, A. D. (1991). Diathesis-stress theories in the context of life stress research: Implications for the depressive disorders.Psychological Bulletin, 110(3), 406-425.
[38] Moore C. M., Jacobson S. A., & Fingerlin T. E. (2020). Power and sample size calculations for genetic association studies in the presence of genetic model mis-specification.Human Heredity, 84(6), 256-271.
[39] Mueller A., Strahler J., Armbruster D., Lesch K. P., Brocke B., & Kirschbaum C. (2012). Genetic contributions to acute autonomic stress responsiveness in children.International Journal of Psychophysiology, 83(3), 302-308.
[40] Mueller B., Figueroa A., & Robinson-Papp J. (2022). Structural and functional connections between the autonomic nervous system, hypothalamic-pituitary-adrenal axis, and the immune system: A context and time dependent stress response network.Neurological Sciences, 43(2), 951-960.
[41] Muntner P., Shimbo D., Carey R. M., Charleston J., Gaillard T., Misra S., … Schwartz J. E. (2019). Measurement of blood pressure in humans: A scientific statement from the American Heart Association.Hypertension, 73(5), e35-e66.
[42] O’Riordan A., Howard S., & Gallagher S. (2023). Blunted cardiovascular reactivity to psychological stress and prospective health: A systematic review.Health Psychology Review, 17(1), 121-147.
[43] Oswald L. M., McCaul M., Choi L., Yang X., & Wand G. S. (2004). Catechol-O-methyltransferase polymorphism alters hypothalamic-pituitary-adrenal axis responses to naloxone: A preliminary report.Biological Psychiatry, 55(1), 102-105.
[44] Phillips A. C.(2015). Stress and Cardiovascular Reactivity. In: Alvarenga, M., Byrne, D. (Eds.), Handbook of psychocardiology (pp. 1-15). Springer, Singapore.
[45] Pluess, M. (2015). Individual differences in environmental sensitivity.Child Development Perspectives, 9(3), 138-143.
[46] Politi C., Roumeliotis S., Tripepi G., & Spoto B. (2023). Sample size calculation in genetic association studies: A practical approach. Life, 13(1), 235.
[47] Stocker C. M., Masarik A. S., Widaman K. F., Reeb B. T., Boardman J. D., Smolen A., … Conger K. J. (2017). Parenting and adolescents’ psychological adjustment: Longitudinal moderation by adolescents’ genetic sensitivity.Development and Psychopathology, 29(4), 1289-1304.
[48] Strotsava, M., & Brindle, R. C. (2025). Adverse childhood experiences do not relate to cardiovascular or baroreflex reactivity to acute mental stress in the laboratory. International Journal of Psychophysiology, 216, 113250.
[49] Sumner J. A., McLaughlin K. A., Walsh K., Sheridan M. A., & Koenen K. C. (2015). Caregiving and 5‐HTTLPR genotype predict adolescent physiological stress reactivity: Confirmatory tests of gene×environment interactions.Child Development, 86(4), 985-994.
[50] Tyrka A. R., Ridout K. K., & Parade S. H. (2016). Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults.Development and Psychopathology, 28(4), 1319-1331.
[51] Urbina-Johanson, S. A., Meza, R., Martin, P., Fearey, E., Lambert, H., & McLaughlin, K. A. (2025). Childhood trauma as a public health issue. In: Landolt, M.A., Cloitre, M., Schnyder, U. (Eds.), Evidence-based treatments for trauma-related disorders in children and adolescents (pp. 59-79). Cham: Springer Nature Switzerland.
[52] Wang X., Ding F., Cheng C., He J., Wang X., & Yao S. (2022). Psychometric properties and measurement invariance of the Childhood Trauma Questionnaire (Short Form) across genders, time points and presence of major depressive disorder among Chinese adolescents.Frontiers in Psychology, 13, 816051.
[53] Watters E. R., Aloe A. M., & Wojciak A. S. (2023). Examining the associations between childhood trauma, resilience, and depression: A multivariate meta-analysis.Trauma, Violence, & Abuse, 24(1), 231-244.
[54] Wendel C. J., Cundiff J. M., Cribbet M. R., & DeCaro J. A. (2023). Early adversity and cardiovascular stress response: Stress reactivity or sensitivity to context.Health Psychology, 42(9), 642-656.
[55] Woody A., Hooker E. D., Zoccola P. M., & Dickerson S. S. (2018). Social-evaluative threat, cognitive load, and the cortisol and cardiovascular stress response. Psychoneuroendocrinology, 97, 149-155.
[56] Widaman K. F., Helm J. L., Castro-Schilo L., Pluess M., Stallings M. C., & Belsky J. (2012). Distinguishing ordinal and disordinal interactions.Psychological Methods, 17(4), 615-622.
[57] Zhang, Y., & Lü, W. (2022). Effect of childhood maltreatment on cardiovascular response habitation to repeated psychosocial stress. International Journal of Psychophysiology, 172, 10-16.