Pathways from Adverse Childhood Experiences to Nervous System Dysregulation

Cynthia R. Rovnaghi, Kanwaljeet J. S. Anand


The type, timing, duration and frequency of exposures to adverse childhood experiences (ACEs) or early life stresses (prenatal/postnatal) are likely antecedents of nervous system dysregulation manifesting across multiple systems. These are mediated through multiple neuroendocrine axes(hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, pituitary-growth hormone/insulin-like growth factor-1 (IGF), hypothalamic-pituitary-gonadal) and the autonomic system(sympathetic or parasympathetic), but also affect neuro-immune interactions (innate and adaptive immunity) and the neuroenteric system(gastric, intestinal, and hepato-pancreatic). 

Even in the absence of abuse or neglect, children are increasingly exposed to three overarching trends: 1) parental use of psychotropic drugs and substances; 2) inconsistent or distracted parenting; and 3) deprivation from natural environments, social engagements, and unstructured non-technologically-dependent play.  These children may fail to acquire developmentally appropriate self-regulation, coping skills, or peer engagement skills; they often receive pharmaceuticals for behavioral compliance, as opposed to mindfulness, self-reflection, or cognitive-behavioral therapy to guide self-development. Children presenting with clinically unexplained symptoms across multiple domains (executive dysfunction, sleep disturbances, autonomic dysregulation, somatization, digestive symptoms, emotional dysregulation) are susceptible to permanent reductions in grey matter volume, cognitive/behavioral problems, and poorer physical and mental health.  Stress from early childhood adversity disrupts their first-time learning experiences; acclimatizes them toward pathways of either positive (supportive, nurturing) or negative (fear inducing) reinforcement of affiliated experiences, internalizing or externalizing behaviors, and impaired self-regulation.  


Stress systems, Central Nervous System (CNS) dysregulation, Hypothalamic-Pituitary-Adrenal (HPA) Axis, Hypothalamic-Pituitary-Thyroid (HPT) Axis, Hypothalamic-Pituitary-Gonadal (HPG) axis, Autonomic Nervous System, clinical domains, early life stress

Full Text:



Elbers J, Rovnaghi, C.R., Golianu, B., and Anand, K.J.S. Clinical Profile Associated with Adverse Childhood Experiences: The Advent of Nervous System Dysregulation. Children. 2017;4(98).

Charmandari E, Kino T, Souvatzoglou E, Chrousos GP. Pediatric stress: hormonal mediators and human development. Horm Res. 2003;59(4):161-79.

Garner AS, Shonkoff JP. , Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood, Adoption, and Dependent Care; Section on Developmental and Behavioral Pediatrics. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health. Pediatrics. 2012;129(1):e224-31.

Johnson SB, Riley AW, Granger DA, Riis J. The science of early life toxic stress for pediatric practice and advocacy. Pediatrics. 2013;131(2):319-27.

Jessop DS, Turner-Cobb JM. Measurement and meaning of salivary cortisol: a focus on health and disease in children. Stress. 2008;11(1):1-14.

Coupe P, Catheline G, Lanuza E, Manjon JV, Alzheimer's Disease Neuroimaging I. Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis. Hum Brain Mapp. 2017;38(11):5501-18.

Keresztes A, Bender AR, Bodammer NC, Lindenberger U, Shing YL, Werkle-Bergner M. Hippocampal maturity promotes memory distinctiveness in childhood and adolescence. Proc Natl Acad Sci U S A. 2017;114(34):9212-7.

Lo Iacono L, Carola V. The impact of adolescent stress experiences on neurobiological development. Semin Cell Dev Biol. 2018;77:93-103.

Ortega-Martinez S. Influences of prenatal and postnatal stress on adult hippocampal neurogenesis: the double neurogenic niche hypothesis. Behav Brain Res. 2015;281:309-17.

Keding TJ, Herringa RJ. Abnormal structure of fear circuitry in pediatric post-traumatic stress disorder. Neuropsychopharmacology. 2015;40(3):537-45.

Felitti VJ. Adverse childhood experiences and adult health. Acad Pediatr. 2009;9(3):131-2.

Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-58.

Stirrat LI, Sengers BG, Norman JE, Homer NZM, Andrew R, Lewis RM, et al. Transfer and Metabolism of Cortisol by the Isolated Perfused Human Placenta. J Clin Endocrinol Metab. 2018;103(2):640-8.

Popp J, Wolfsgruber S, Heuser I, Peters O, Hull M, Schroder J, et al. Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type. Neurobiol Aging. 2015;36(2):601-7.

Aas M, Dazzan P, Mondelli V, Toulopoulou T, Reichenberg A, Di Forti M, et al. Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis. Psychol Med. 2011;41(3):463-76.

Kao K, Doan SN, St John AM, Meyer JS, Tarullo AR. Salivary cortisol reactivity in preschoolers is associated with hair cortisol and behavioral problems. Stress. 2018;21(1):28-35.

King LS, Colich NL, LeMoult J, Humphreys KL, Ordaz SJ, Price AN, et al. The impact of the severity of early life stress on diurnal cortisol: The role of puberty. Psychoneuroendocrinology. 2017;77:68-74.

England-Mason G, Kimber M, Khoury J, Atkinson L, MacMillan H, Gonzalez A. Difficulties with emotion regulation moderate the association between childhood history of maltreatment and cortisol reactivity to psychosocial challenge in postpartum women. Horm Behav. 2017;95:44-56.

Yong Ping E, Laplante DP, Elgbeili G, Hillerer KM, Brunet A, O'Hara MW, et al. Prenatal maternal stress predicts stress reactivity at 2(1/2) years of age: the Iowa Flood Study. Psychoneuroendocrinology. 2015;56:62-78.

Bellinger DL, Lubahn C, Lorton D. Maternal and early life stress effects on immune function: relevance to immunotoxicology. J Immunotoxicol. 2008;5(4):419-44.

Rosenblat JD, Cha DS, Mansur RB, McIntyre RS. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014;53:23-34.

Keenan K, Hipwell A, Babinski D, Bortner J, Henneberger A, Hinze A, et al. Examining the developmental interface of cortisol and depression symptoms in young adolescent girls. Psychoneuroendocrinology. 2013;38(10):2291-9.

De Bellis MD, Baum AS, Birmaher B, Keshavan MS, Eccard CH, Boring AM, et al. A.E. Bennett Research Award. Developmental traumatology. Part I: Biological stress systems. Biol Psychiatry. 1999;45(10):1259-70.

De Bellis MD, Keshavan MS, Clark DB, Casey BJ, Giedd JN, Boring AM, et al. A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development. Biol Psychiatry. 1999;45(10):1271-84.

De Bellis MD, Keshavan MS, Shifflett H, Iyengar S, Dahl RE, Axelson DA, et al. Superior temporal gyrus volumes in pediatric generalized anxiety disorder. Biol Psychiatry. 2002;51(7):553-62.

Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP. Developmental neurobiology of childhood stress and trauma. Psychiatr Clin North Am. 2002;25(2):397-426, vii-viii.

Charil A, Laplante DP, Vaillancourt C, King S. Prenatal stress and brain development. Brain Res Rev. 2010;65(1):56-79.

McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007;87(3):873-904.

Pearson J, Tarabulsy GM, Bussieres EL. Foetal programming and cortisol secretion in early childhood: A meta-analysis of different programming variables. Infant Behav Dev. 2015;40:204-15.

Keller-Wood M. Hypothalamic-Pituitary--Adrenal Axis-Feedback Control. Compr Physiol. 2015;5(3):1161-82.

Rovnaghi CR, Kala AF, Allen SL, Anand KJS. Interpretation of cortisol concentrations and reference intervals from the CALIPER database. Clin Chem. 2014;60(2):418-9.

Aguilera G. HPA axis responsiveness to stress: implications for healthy aging. Exp Gerontol. 2011;46(2-3):90-5.

Glynn LM, Davis EP, Sandman CA. New insights into the role of perinatal HPA-axis dysregulation in postpartum depression. Neuropeptides. 2013;47(6):363-70.

Crews D, Gillette R, Scarpino SV, Manikkam M, Savenkova MI, Skinner MK. Epigenetic transgenerational inheritance of altered stress responses. Proc Natl Acad Sci U S A. 2012;109(23):9143-8.

Serova LI, Gueorguiev V, Cheng SY, Sabban EL. Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism. Neuroscience. 2008;153(4):1380-9.

Fenoglio KA, Chen Y, Baram TZ. Neuroplasticity of the hypothalamic-pituitary-adrenal axis early in life requires recurrent recruitment of stress-regulating brain regions. J Neurosci. 2006;26(9):2434-42.

Feldman R. Oxytocin and social affiliation in humans. Horm Behav. 2012;61(3):380-91.

Atzil S, Hendler T, Zagoory-Sharon O, Winetraub Y, Feldman R. Synchrony and specificity in the maternal and the paternal brain: relations to oxytocin and vasopressin. J Am Acad Child Adolesc Psychiatry. 2012;51(8):798-811.

Feldman R. Sensitive periods in human social development: New insights from research on oxytocin, synchrony, and high-risk parenting. Dev Psychopathol. 2015;27(2):369-95.

Feldman R. The neurobiology of mammalian parenting and the biosocial context of human caregiving. Horm Behav. 2016;77:3-17.

Feldman R, Bakermans-Kranenburg MJ. Oxytocin: a parenting hormone. Curr Opin Psychol. 2017;15:13-8.

Heinrichs M, Meinlschmidt G, Neumann I, Wagner S, Kirschbaum C, Ehlert U, et al. Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women. J Clin Endocrinol Metab. 2001;86(10):4798-804.

Acheson D, Feifel D, de Wilde S, McKinney R, Lohr J, Risbrough V. The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample. Psychopharmacology (Berl). 2013;229(1):199-208.

Isbir GG, Sercekus P. The Effects of Intrapartum Supportive Care on Fear of Delivery and Labor Outcomes: A Single-Blind Randomized Controlled Trial. J Nurs Res. 2017;25(2):112-9.

Seltzer LJ, Ziegler T, Connolly MJ, Prososki AR, Pollak SD. Stress-induced elevation of oxytocin in maltreated children: evolution, neurodevelopment, and social behavior. Child Dev. 2014;85(2):501-12.

Cooke BM, Weathington JM. Human and animal research into sex-specific effects of child abuse. Horm Behav. 2014;65(4):416-26.

Brewer-Smyth K, Burgess AW. Childhood sexual abuse by a family member, salivary cortisol, and homicidal behavior of female prison inmates. Nurs Res. 2008;57(3):166-74.

Wosu AC, Gelaye B, Williams MA. Childhood sexual abuse and posttraumatic stress disorder among pregnant and postpartum women: review of the literature. Arch Womens Ment Health. 2015;18(1):61-72.

Theall KP, Shirtcliff EA, Dismukes AR, Wallace M, Drury SS. Association Between Neighborhood Violence and Biological Stress in Children. JAMA Pediatr. 2017;171(1):53-60.

Palmer FB, Anand KJ, Graff JC, Murphy LE, Qu Y, Volgyi E, et al. Early adversity, socioemotional development, and stress in urban 1-year-old children. The Journal of pediatrics. 2013;163(6):1733-9 e1.

Elling L, Schupp H, Bayer J, Brockelmann AK, Steinberg C, Dobel C, et al. The impact of acute psychosocial stress on magnetoencephalographic correlates of emotional attention and exogenous visual attention. PloS one. 2012;7(6):e35767.

Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: Outcomes. Nat Rev Endocrinol. 2014;10(7):391-402.

Baker ME, Nelson DR, Studer RA. Origin of the response to adrenal and sex steroids: Roles of promiscuity and co-evolution of enzymes and steroid receptors. J Steroid Biochem Mol Biol. 2015;151:12-24.

Demura M, Demura Y, Takeda Y, Saijoh K. Dynamic regulation of the angiotensinogen gene by DNA methylation, which is influenced by various stimuli experienced in daily life. Hypertens Res. 2015;38(8):519-27.

Fuqua JS, Rogol AD. Neuroendocrine alterations in the exercising human: implications for energy homeostasis. Metabolism. 2013;62(7):911-21.

Gibbison B, Angelini GD, Lightman SL. Dynamic output and control of the hypothalamic-pituitary-adrenal axis in critical illness and major surgery. Br J Anaesth. 2013;111(3):347-60.

Narita K, Fujihara K, Takei Y, Suda M, Aoyama Y, Uehara T, et al. Associations among parenting experiences during childhood and adolescence, hypothalamus-pituitary-adrenal axis hypoactivity, and hippocampal gray matter volume reduction in young adults. Hum Brain Mapp. 2012;33(9):2211-23.

Reynolds RM. Glucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis--2012 Curt Richter Award Winner. Psychoneuroendocrinology. 2013;38(1):1-11.

Struber N, Struber D, Roth G. Impact of early adversity on glucocorticoid regulation and later mental disorders. Neurosci Biobehav Rev. 2014;38:17-37.

Bennett GA, Palliser HK, Shaw JC, Walker D, Hirst JJ. Prenatal Stress Alters Hippocampal Neuroglia and Increases Anxiety in Childhood. Dev Neurosci. 2015;37(6):533-45.

Fatima M, Srivastav S, Mondal AC. Prenatal stress and depression associated neuronal development in neonates. Int J Dev Neurosci. 2017;60:1-7.

Hruska B, Cullen PK, Delahanty DL. Pharmacological modulation of acute trauma memories to prevent PTSD: considerations from a developmental perspective. Neurobiol Learn Mem. 2014;112:122-9.

Jones T, Moller MD. Implications of hypothalamic-pituitary-adrenal axis functioning in posttraumatic stress disorder. J Am Psychiatr Nurses Assoc. 2011;17(6):393-403.

Turner-Cobb JM. Psychological and stress hormone correlates in early life: a key to HPA-axis dysregulation and normalisation. Stress. 2005;8(1):47-57.

Kalmakis KA, Meyer JS, Chiodo L, Leung K. Adverse childhood experiences and chronic hypothalamic-pituitary-adrenal activity. Stress. 2015;18(4):446-50.

Karlen J, Frostell A, Theodorsson E, Faresjo T, Ludvigsson J. Maternal influence on child HPA axis: a prospective study of cortisol levels in hair. Pediatrics. 2013;132(5):e1333-40.

Gonzalez A, Jenkins JM, Steiner M, Fleming AS. Maternal early life experiences and parenting: the mediating role of cortisol and executive function. J Am Acad Child Adolesc Psychiatry. 2012;51(7):673-82.

Ehlert U. Enduring psychobiological effects of childhood adversity. Psychoneuroendocrinology. 2013;38(9):1850-7.

Keeshin BR, Strawn JR, Out D, Granger DA, Putnam FW. Cortisol awakening response in adolescents with acute sexual abuse related posttraumatic stress disorder. Depress Anxiety. 2014;31(2):107-14.

Dettmer AM, Wooddell LJ, Rosenberg KL, Kaburu SS, Novak MA, Meyer JS, et al. Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys. Soc Neurosci. 2016:1-10.

Reichl C, Heyer A, Brunner R, Parzer P, Volker JM, Resch F, et al. Hypothalamic-pituitary-adrenal axis, childhood adversity and adolescent nonsuicidal self-injury. Psychoneuroendocrinology. 2016;74:203-11.

Dallman MF, Pecoraro NC, La Fleur SE, Warne JP, Ginsberg AB, Akana SF, et al. Glucocorticoids, chronic stress, and obesity. Prog Brain Res. 2006;153:75-105.

Dallman MF, Akana SF, Pecoraro NC, Warne JP, la Fleur SE, Foster MT. Glucocorticoids, the etiology of obesity and the metabolic syndrome. Curr Alzheimer Res. 2007;4(2):199-204.

Shenk CE, Noll JG, Putnam FW, Trickett PK. A prospective examination of the role of childhood sexual abuse and physiological asymmetry in the development of psychopathology. Child Abuse Negl. 2010;34(10):752-61.

Hillis SD, Anda RF, Felitti VJ, Marchbanks PA. Adverse childhood experiences and sexual risk behaviors in women: a retrospective cohort study. Fam Plann Perspect. 2001;33(5):206-11.

Mersky JP, Topitzes J, Reynolds AJ. Impacts of adverse childhood experiences on health, mental health, and substance use in early adulthood: a cohort study of an urban, minority sample in the U.S. Child Abuse Negl. 2013;37(11):917-25.

Brown DW, Anda RF, Tiemeier H, Felitti VJ, Edwards VJ, Croft JB, et al. Adverse childhood experiences and the risk of premature mortality. Am J Prev Med. 2009;37(5):389-96.

Campbell JA, Walker RJ, Egede LE. Associations Between Adverse Childhood Experiences, High-Risk Behaviors, and Morbidity in Adulthood. Am J Prev Med. 2016;50(3):344-52.

Sharp H, Pickles A, Meaney M, Marshall K, Tibu F, Hill J. Frequency of infant stroking reported by mothers moderates the effect of prenatal depression on infant behavioural and physiological outcomes. PLoS One. 2012;7(10):e45446.

Pawluski JL, Brain UM, Underhill CM, Hammond GL, Oberlander TF. Prenatal SSRI exposure alters neonatal corticosteroid binding globulin, infant cortisol levels, and emerging HPA function. Psychoneuroendocrinology. 2012;37(7):1019-28.

Weinstock M. Intrauterine factors as determinants of depressive disorder. Isr J Psychiatry Relat Sci. 2010;47(1):36-45.

de Bruijn AT, van Bakel HJ, Wijnen H, Pop VJ, van Baar AL. Prenatal maternal emotional complaints are associated with cortisol responses in toddler and preschool aged girls. Dev Psychobiol. 2009;51(7):553-63.

Van den Bergh BR, Van Calster B, Smits T, Van Huffel S, Lagae L. Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: a prospective study on the fetal origins of depressed mood. Neuropsychopharmacology. 2008;33(3):536-45.

Kaplan LA, Evans L, Monk C. Effects of mothers' prenatal psychiatric status and postnatal caregiving on infant biobehavioral regulation: can prenatal programming be modified? Early Hum Dev. 2008;84(4):249-56.

Talge NM, Neal C, Glover V, Early Stress TR, Prevention Science Network F, Neonatal Experience on C, et al. Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry. 2007;48(3-4):245-61.

Kammerer M, Taylor A, Glover V. The HPA axis and perinatal depression: a hypothesis. Arch Womens Ment Health. 2006;9(4):187-96.

Vidali S, Knuever J, Lerchner J, Giesen M, Biro T, Klinger M, et al. Hypothalamic-pituitary-thyroid axis hormones stimulate mitochondrial function and biogenesis in human hair follicles. J Invest Dermatol. 2014;134(1):33-42.

Gil-Ibanez P, Garcia-Garcia F, Dopazo J, Bernal J, Morte B. Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types. Cereb Cortex. 2017;27(1):706-17.

Daimon CM, Chirdon P, Maudsley S, Martin B. The role of Thyrotropin Releasing Hormone in aging and neurodegenerative diseases. Am J Alzheimers Dis (Columbia). 2013;1(1).

Wang S. Traumatic stress and attachment. Acta Physiol Scand Suppl. 1997;640:164-9.

Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865-71.

Wang S. Traumatic stress and thyroid function. Child Abuse Negl. 2006;30(6):585-8.

Morillo E, Gardner LI. Bereavement as an antecedent factor in thyrotoxicosis of childhood: four case studies with survey of possible metabolic pathways. Psychosom Med. 1979;41(7):545-55.

Morillo E, Gardner LI. Activation of latent Graves' disease in children. Review of possible psychosomatic mechanisms. Clin Pediatr (Phila). 1980;19(3):160-3.

Machado TD, Salum GA, Bosa VL, Goldani MZ, Meaney MJ, Agranonik M, et al. Early life trauma is associated with decreased peripheral levels of thyroid-hormone T3 in adolescents. Int J Dev Neurosci. 2015;47(Pt B):304-8.

Haviland MG, Sonne JL, Anderson DL, Nelson JC, Sheridan-Matney C, Nichols JG, et al. Thyroid hormone levels and psychological symptoms in sexually abused adolescent girls. Child Abuse Negl. 2006;30(6):589-98.

Plaza A, Garcia-Esteve L, Torres A, Ascaso C, Gelabert E, Luisa Imaz M, et al. Childhood physical abuse as a common risk factor for depression and thyroid dysfunction in the earlier postpartum. Psychiatry Res. 2012;200(2-3):329-35.

Plaza A, Garcia-Esteve L, Ascaso C, Navarro P, Gelabert E, Halperin I, et al. Childhood sexual abuse and hypothalamus-pituitary-thyroid axis in postpartum major depression. J Affect Disord. 2010;122(1-2):159-63.

Bunevicius A, Leserman J, Girdler SS. Hypothalamic-pituitary-thyroid axis function in women with a menstrually related mood disorder: association with histories of sexual abuse. Psychosom Med. 2012;74(8):810-6.

Sinai C, Hirvikoski T, Nordstrom AL, Nordstrom P, Nilsonne A, Wilczek A, et al. Hypothalamic pituitary thyroid axis and exposure to interpersonal violence in childhood among women with borderline personality disorder. Eur J Psychotraumatol. 2014;5.

Friedman MJ, Wang S, Jalowiec JE, McHugo GJ, McDonagh-Coyle A. Thyroid hormone alterations among women with posttraumatic stress disorder due to childhood sexual abuse. Biol Psychiatry. 2005;57(10):1186-92.

Brook CG. Mechanism of puberty. Horm Res. 1999;51 Suppl 3:52-4.

Ishunina TA, Swaab DF. Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex. J Clin Endocrinol Metab. 1999;84(12):4637-44.

Roa J, Garcia-Galiano D, Castellano JM, Gaytan F, Pinilla L, Tena-Sempere M. Metabolic control of puberty onset: new players, new mechanisms. Mol Cell Endocrinol. 2010;324(1-2):87-94.

Geraghty AC, Kaufer D. Glucocorticoid Regulation of Reproduction. Adv Exp Med Biol. 2015;872:253-78.

Ubuka T, Parhar IS, Tsutsui K. Gonadotropin-inhibitory hormone mediates behavioral stress responses. Gen Comp Endocrinol. 2018;265:202-6.

Faykoo-Martinez M, Monks DA, Zovkic IB, Holmes MM. Sex- and brain region-specific patterns of gene expression associated with socially-mediated puberty in a eusocial mammal. PLoS One. 2018;13(2):e0193417.

Calisi RM, Austin SH, Lang AS, MacManes MD. Sex-biased transcriptomic response of the reproductive axis to stress. Horm Behav. 2018;100:56-68.

Acevedo-Rodriguez A, Kauffman AS, Cherrington BD, Borges CS, Roepke TA, Laconi M. Emerging insights into hypothalamic-pituitary-gonadal axis regulation and interaction with stress signalling. J Neuroendocrinol. 2018:e12590.

Nargund VH. Effects of psychological stress on male fertility. Nat Rev Urol. 2015;12(7):373-82.

Slopen N, Roberts AL, LeWinn KZ, Bush NR, Rovnaghi CR, Tylavsky F, et al. Maternal experiences of trauma and hair cortisol in early childhood in a prospective cohort. Psychoneuroendocrinology. 2018;98:168-76.

Nguyen TV, Jones SL, Elgbeili G, Monnier P, Yu C, Laplante DP, et al. Testosterone-cortisol dissociation in children exposed to prenatal maternal stress, and relationship with aggression: Project Ice Storm. Dev Psychopathol. 2018;30(3):981-94.

Duchesne A, Liu A, Jones SL, Laplante DP, King S. Childhood body mass index at 5.5 years mediates the effect of prenatal maternal stress on daughters' age at menarche: Project Ice Storm. J Dev Orig Health Dis. 2017;8(2):168-77.

Boynton-Jarrett R, Wright RJ, Putnam FW, Lividoti Hibert E, Michels KB, Forman MR, et al. Childhood abuse and age at menarche. J Adolesc Health. 2013;52(2):241-7.

Mendle J, Leve LD, Van Ryzin M, Natsuaki MN, Ge X. Associations Between Early Life Stress, Child Maltreatment, and Pubertal Development Among Girls in Foster Care. J Res Adolesc. 2011;21(4):871-80.

Belsky J, Steinberg L, Houts RM, Halpern-Felsher BL, Network NECCR. The development of reproductive strategy in females: early maternal harshness --> earlier menarche --> increased sexual risk taking. Dev Psychol. 2010;46(1):120-8.

Dismukes AR, Shirtcliff EA, Hanson JL, Pollak SD. Context influences the interplay of endocrine axes across the day. Dev Psychobiol. 2015;57(6):731-41.

Allwood MA, Handwerger K, Kivlighan KT, Granger DA, Stroud LR. Direct and moderating links of salivary alpha-amylase and cortisol stress-reactivity to youth behavioral and emotional adjustment. Biol Psychol. 2011;88(1):57-64.

Paszynska E, Dmitrzak-Weglarz M, Tyszkiewicz-Nwafor M, Slopien A. Salivary alpha-amylase, secretory IgA and free cortisol as neurobiological components of the stress response in the acute phase of anorexia nervosa. World J Biol Psychiatry. 2016;17(4):266-73.

Giesbrecht GF, Campbell T, Letourneau N, Team APS. Sexually dimorphic adaptations in basal maternal stress physiology during pregnancy and implications for fetal development. Psychoneuroendocrinology. 2015;56:168-78.

Zheng X, Chen Y, Du J. Recent advances in the understanding of the mechanisms underlying postural tachycardia syndrome in children: practical implications for treatment. Cardiol Young. 2017;27(3):413-7.

Weese-Mayer DE, Rand CM, Zhou A, Carroll MS, Hunt CE. Congenital central hypoventilation syndrome: a bedside-to-bench success story for advancing early diagnosis and treatment and improved survival and quality of life. Pediatr Res. 2017;81(1-2):192-201.

Charnay AJ, Antisdel-Lomaglio JE, Zelko FA, Rand CM, Le M, Gordon SC, et al. Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children. Chest. 2016;149(3):809-15.

Ibanez-Mico S, Marcos Oltra AM, de Murcia Lemauviel S, Ruiz Pruneda R, Martinez Ferrandez C, Domingo Jimenez R. Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review. Neurologia. 2017;32(9):616-22.

Reppucci D, Hamilton J, Yeh EA, Katz S, Al-Saleh S, Narang I. ROHHAD syndrome and evolution of sleep disordered breathing. Orphanet J Rare Dis. 2016;11(1):106.

Jacobson LA, Rane S, McReynolds LJ, Steppan DA, Chen AR, Paz-Priel I. Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide. Pediatrics. 2016;138(1).

Topcu B, Akalin F. The autonomic nervous system dysregulation in response to orthostatic stress in children with neurocardiogenic syncope. Cardiol Young. 2010;20(2):165-72.

Hasler WL, Li BU, Koch KL, Parkman HP, Kovacic K, McCallum RW. Methodologic considerations for studies of chronic nausea and vomiting in adults and children. Auton Neurosci. 2017;202:28-39.

Henry BL, Minassian A, Paulus MP, Geyer MA, Perry W. Heart rate variability in bipolar mania and schizophrenia. J Psychiatr Res. 2010;44(3):168-76.

Sowder E, Gevirtz R, Shapiro W, Ebert C. Restoration of vagal tone: a possible mechanism for functional abdominal pain. Appl Psychophysiol Biofeedback. 2010;35(3):199-206.

Tietjen GE. Childhood Maltreatment and Headache Disorders. Curr Pain Headache Rep. 2016;20(4):26.

Wyller VB, Evang JA, Godang K, Solhjell KK, Bollerslev J. Hormonal alterations in adolescent chronic fatigue syndrome. Acta Paediatr. 2010;99(5):770-3.

Dileo JF, Brewer W, Northam E, Yucel M, Anderson V. Investigating the neurodevelopmental mediators of aggression in children with a history of child maltreatment:An exploratory field study. Child Neuropsychol. 2017;23(6):655-77.

Busso DS, McLaughlin KA, Sheridan MA. Dimensions of Adversity, Physiological Reactivity, and Externalizing Psychopathology in Adolescence: Deprivation and Threat. Psychosom Med. 2017;79(2):162-71.

Shenk CE, Griffin AM, O'Donnell KJ. Symptoms of major depressive disorder subsequent to child maltreatment: Examining change across multiple levels of analysis to identify transdiagnostic risk pathways. Dev Psychopathol. 2015;27(4 Pt 2):1503-14.

Leitzke BT, Hilt LM, Pollak SD. Maltreated youth display a blunted blood pressure response to an acute interpersonal stressor. J Clin Child Adolesc Psychol. 2015;44(2):305-13.

Skowron EA, Loken E, Gatzke-Kopp LM, Cipriano-Essel EA, Woehrle PL, Van Epps JJ, et al. Mapping cardiac physiology and parenting processes in maltreating mother-child dyads. J Fam Psychol. 2011;25(5):663-74.

Ford JD, Fraleigh LA, Albert DB, Connor DF. Child abuse and autonomic nervous system hyporesponsivity among psychiatrically impaired children. Child Abuse Negl. 2010;34(7):507-15.

Miller GE, Chen E, Parker KJ. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol Bull. 2011;137(6):959-97.

Bunea IM, Szentagotai-Tatar A, Miu AC. Early-life adversity and cortisol response to social stress: a meta-analysis. Transl Psychiatry. 2017;7(12):1274.

Bernard K, Frost A, Bennett CB, Lindhiem O. Maltreatment and diurnal cortisol regulation: A meta-analysis. Psychoneuroendocrinology. 2017;78:57-67.

Schechter DS, Moser DA, Paoloni-Giacobino A, Stenz L, Gex-Fabry M, Aue T, et al. Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure. Front Psychol. 2015;6:690.

Bernard K, Zwerling J, Dozier M. Effects of early adversity on young children's diurnal cortisol rhythms and externalizing behavior. Dev Psychobiol. 2015;57(8):935-47.

Doom JR, Cicchetti D, Rogosch FA. Longitudinal patterns of cortisol regulation differ in maltreated and nonmaltreated children. J Am Acad Child Adolesc Psychiatry. 2014;53(11):1206-15.

Gonzalez A. The impact of childhood maltreatment on biological systems: Implications for clinical interventions. Paediatr Child Health. 2013;18(8):415-8.

Shea A, Walsh C, Macmillan H, Steiner M. Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females. Psychoneuroendocrinology. 2005;30(2):162-78.

Van Voorhees E, Scarpa A. The effects of child maltreatment on the hypothalamic-pituitary-adrenal axis. Trauma Violence Abuse. 2004;5(4):333-52.

Angelovski A, Sattel H, Henningsen P, Sack M. Heart rate variability predicts therapy outcome in pain-predominant multisomatoform disorder. J Psychosom Res. 2016;83:16-21.

Coyas A, Stavrou J, Antonakopoulos C. Vasomotor rhinitis: psychosomatic conditions and treatment. Rhinology. 1976;14(4):177-80.

Gulewitsch MD, Jusyte A, Mazurak N, Weimer K, Schonenberg M. Preliminary evidence for increased parasympathetic activity during social inclusion and exclusion in adolescents with functional abdominal pain. J Psychosom Res. 2017;98:106-12.

Meyer PW, Muller LE, Zastrow A, Schmidinger I, Bohus M, Herpertz SC, et al. Heart rate variability in patients with post-traumatic stress disorder or borderline personality disorder: relationship to early life maltreatment. J Neural Transm (Vienna). 2016;123(9):1107-18.

Nakada Y. A study of psychosocial factors in the psychosomatic symptoms of adolescents in Okinawa. Acta Paediatr Jpn. 1992;34(3):301-9.

Radziej K, Schmid G, Dinkel A, Zwergal A, Lahmann C. Psychological traumatization and adverse life events in patients with organic and functional vestibular symptoms. J Psychosom Res. 2015;79(2):123-9.

Tanaka H, Borres M, Thulesius O, Tamai H, Ericson MO, Lindblad LE. Evidence of decreased sympathetic function in children with psychosomatic symptoms. Clin Auton Res. 2002;12(6):477-82.

Thome J, Densmore M, Frewen PA, McKinnon MC, Theberge J, Nicholson AA, et al. Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder. Hum Brain Mapp. 2017;38(1):27-40.

Wenger MA. Studies of autonomic balance: a summary. Psychophysiology. 1966;2(3):173-86.

Garner AS, Shonkoff JP, Committee on Psychosocial Aspects of C, Family H, Committee on Early Childhood A, Dependent C, et al. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health. Pediatrics. 2012;129(1):e224-31.

Golier JA, Caramanica K, Michaelides AC, Makotkine I, Schmeidler J, Harvey PD, et al. A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness. Psychoneuroendocrinology. 2016;64:22-30.

Anda RF, Brown DW, Felitti VJ, Dube SR, Giles WH. Adverse childhood experiences and prescription drug use in a cohort study of adult HMO patients. BMC Public Health. 2008;8:198.

Gartstein MA, Hookenson KV, Brain U, Devlin AM, Grunau RE, Oberlander TF. Sculpting infant soothability: the role of prenatal SSRI antidepressant exposure and neonatal SLC6A4 methylation status. Dev Psychobiol. 2016;58(6):745-58.

Rotem-Kohavi N, Oberlander TF. Variations in Neurodevelopmental Outcomes in Children with Prenatal SSRI Antidepressant Exposure. Birth Defects Res. 2017;109(12):909-23.

Elmasry H, Goodwin RD, Terry MB, Tehranifar P. Early life exposure to cigarette smoke and depressive symptoms among women in midlife. Nicotine Tob Res. 2014;16(10):1298-306.

Roberts KH, Munafo MR, Rodriguez D, Drury M, Murphy MF, Neale RE, et al. Longitudinal analysis of the effect of prenatal nicotine exposure on subsequent smoking behavior of offspring. Nicotine Tob Res. 2005;7(5):801-8.

O'Leary CM, Bower C. Guidelines for pregnancy: what's an acceptable risk, and how is the evidence (finally) shaping up? Drug Alcohol Rev. 2012;31(2):170-83.

Rachdaoui N, Sarkar DK. Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System. Alcohol Res. 2017;38(2):255-76.

Tentler JJ, LaPaglia N, Steiner J, Williams D, Castelli M, Kelley MR, et al. Ethanol, growth hormone and testosterone in peripubertal rats. J Endocrinol. 1997;152(3):477-87.

Center for Behavioral Health Statistics and Quality. Key substance use and mental health indicators in the United States: Results from the 2015 National Survey on Drug Use and Health. In: HHS Publication No. SMA 16-4984 NSH-, editor.:; 2016.

Manchikanti L, Boswell MV, Hirsch JA. Lessons learned in the abuse of pain-relief medication: a focus on healthcare costs. Expert Rev Neurother. 2013;13(5):527-43; quiz 44.

Kozhimannil KB, Graves AJ, Jarlenski M, Kennedy-Hendricks A, Gollust S, Barry CL. Non-medical opioid use and sources of opioids among pregnant and non-pregnant reproductive-aged women. Drug Alcohol Depend. 2017;174:201-8.

RTI International RTP, North Carolina. RESULTS FROM THE 2015 NATIONAL SURVEY ON DRUG USE AND HEALTH: DETAILED TABLES. In: Administration SAaMHS, editor.: Center for Behavioral Health Statistics and Quality; 2016.

Li JJ, Lansford JE. A smartphone-based ecological momentary assessment of parental behavioral consistency: Associations with parental stress and child ADHD symptoms. Dev Psychol. 2018;54(6):1086-98.

Radesky JS, Kistin C, Eisenberg S, Gross J, Block G, Zuckerman B, et al. Parent Perspectives on Their Mobile Technology Use: The Excitement and Exhaustion of Parenting While Connected. J Dev Behav Pediatr. 2016;37(9):694-701.

Solomon-Moore E, Sebire SJ, Macdonald-Wallis C, Thompson JL, Lawlor DA, Jago R. Exploring parents' screen-viewing behaviours and sedentary time in association with their attitudes toward their young child's screen-viewing. Prev Med Rep. 2017;7:198-205.

Terras MM, Ramsay J. Family Digital Literacy Practices and Children's Mobile Phone Use. Front Psychol. 2016;7:1957.

Arnsten AF. Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. 2009;10(6):410-22.

Blair C, Raver CC. Individual development and evolution: experiential canalization of self-regulation. Dev Psychol. 2012;48(3):647-57.

Arnsten AF. Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction. CNS Drugs. 2009;23 Suppl 1:33-41.

Tsypes A, Gibb BE. Cognitive vulnerabilities and development of suicidal thinking in children of depressed mothers: A longitudinal investigation. Psychiatry Res. 2016;239:99-104.

Morrongiello BA, Corbett M, Bellissimo A. "Do as I say, not as I do": family influences on children's safety and risk behaviors. Health Psychol. 2008;27(4):498-503.

Orford J, Velleman R. The environmental intergenerational transmission of alcohol problems: a comparison of two hypotheses. Br J Med Psychol. 1991;64 ( Pt 2):189-200.

Pan J, Han W. Exploring the intergenerational persistence of health behaviour: an empirical study of smoking from China. BMC Public Health. 2017;17(1):557.

Wickrama KA, Conger RD, Wallace LE, Elder GH, Jr. The intergenerational transmission of health-risk behaviors: adolescent lifestyles and gender moderating effects. J Health Soc Behav. 1999;40(3):258-72.



  • There are currently no refbacks.
Copyright 2016. All rights reserved.