Abbey Alkon, RN, PNP, MPH, PhD Professor, University of California, San Francisco School of Nursing Lecture at ZHAW Zurich University of Applied Sciences Institute of Nursing, School of Health Professions June 11, 2014 1
Disease Burden: Distribution of Disability-Adjusted Life Years, 2010 11% Non-Communicable Diseases with 7.4% Mental and Behavioral Disorders 35% 54% Communicable, Maternal, Neonatal, and Nutritional Disorders Injuries Murray, Vos, et al., Lancet, 2012; Global Burden of Disease Study; 187 countries. 2
Stress/ Adversity Physical and Mental Health There is a weak relationship between experiencing stress/ adversity and health outcomes. Stress does not always explain why some children have physical and mental health problems. Children s ability to deal with stressors may be different for each child; This is called individual differences.
Stress/ Adversity Physical and Mental Health Individual Differences: Autonomic Nervous System (ANS) Sympathetic Nervous System Parasympathetic Nervous System
image at: anatomy.med.umich.edu/.../autonomics_02.html
Parasympathetic Restorative; rest and digest Constricts pupil Stimulates salivation Slows heart rate Sympathetic Excitatory; fight or flight Dilates pupil Inhibits salivation Increases heart rate image at: parsonsdc.com/faq.aspx
Social experiences, like stress, get under the skin and impact health. There may be sensitive periods when biologic embedding is more potent than other times in life. The process whereby differential human experiences affect the molecular, genomic, and biologic systems that determine expressions of vulnerability and resilience. Ref: Hertzman, C & Boyce, WT (2010) Ann Rev Public Health 31: 329-347. 7
Not all children are equally susceptible to adverse environmental influences. Exposure to adverse, stressful events, such as marital conflict, maternal depression, and financial stress, has been linked to behavior problems and cognitive deficits in children (Boyce, 2007; Burchinal et al., 2000; Essex, et al., 2002; Masten & Shaffer, 2006). Biologically reactive children are particularly responsive to stressful and nurturing experiences (Boyce, 2007; Boyce & Ellis, 2005). 8
Respiratory Sinus Arrhythmia (RSA) Parasympathetic influence on cardiac cycle Measure of heart rate controlling for respirations Inspiratory phase of respiration causes an increase in heart rate Vagal tone, vagal tone index, RSA index Preejection Period (PEP) Sympathetic influence on cardiac cycle Ventricular myocardium is innervated primarily by the sympathetic system Time interval from the filling of left ventricle to opening of aortic valve Measured in milliseconds Ref: Alkon, A. (2012). The Oxford Handbook of Poverty and Child Development, Edited by V. Maholmes & R.B. King. Chapter 12. Oxford University Press. 9
Walter Cannon described the role of the SAM system in the stress response (1914). Known as the fight or flight response Preganglionic sympathetic fibers from the locus coeruleus synapse primarily in the paravertebral ganglia with numerous postsynaptic fibers innervate the visceral organs. An instantaneous, short-lived signal is carried to target organs; this is a fast, diffuse response.
Central Autonomic Function Insular/medial prefrontal cortex Associative, higher cognitive functions Locus coeruleus Activation of the mesocortical/ mesolimbic dopamine systems Amygdala Retrieval and emotional analysis of information; fear circuitry Nucleus of solitary tract Visceroceptive information from CV, respiratory and GI sites Hypothalamus Integrative, homeostatic center
A Biodevelopmental Framework How Early Experiences Get into the Body Shonkoff, J.P., Building a New Biodevelopmental Framework to Guide the Future of Early Childhood Policy. Child Development, January/February 2010, 81 (1): 357 367.
Laboratory Measurement of Psychobiological Reactivity Standardized exposures to social, cognitive, physical and emotional challenges Continuous measures of BP, HR, PEP, RSA Reading of calming stories to acquire resting measures 13
(3 cm.) I e V e V e I e (3 cm.) I = Current (4 ma); V= voltage; Z=impedance (ohms) R = V/I (resistance = voltage/current); dz/dt = change in impedance/time
Type of Task Activity # Minutes Resting Lullaby 1 2 Fear, Startle Jack-in-the-Box 1 Emotion Sick Baby Cry 1 Physical Vibrator 1 Resting Lullaby 2 2 Alkon, A et al. (2006) The ontogeny of autonomic measures in 6- and 12- month old Infants. Developmental Psychobiology. 48: 197-2008. 15
ANS Protocol: 3 to 5 Years Old Task Condition # Minutes Resting Read story aloud 2 Social Interview questions 3 Cognitive Number recall 3 Physical Lemon juice 1 Emotion Videoclips 3 Resting Read story aloud 2 Alkon, A, et al. (2003) Developmental and contextual influences on autonomic Reactivity in young children. Developmental Psychobiology 42: 64-78. Alkon 2011 16
Reactivity Difference Score = response to challenges minus resting state Resting Lullaby, read stories, watching relaxing video before and after the challenging tasks resting score Summary Scores Boyce WT, Alkon A, Chesney M, et al. (1995). Dimensions of psychobiologic reactivity: Cardiovascular responses to laboratory stressors in preschool children. Ann Behav Med 17:315-23. 17
Physiologic Measures Pre-ejection Period (Sympathetic Nervous System) and Respiratory Sinus Arrhythmia (Parasympathetic Nervous System) B RSA R-R interval dz/dt Q Q-B interval PEP Time (msec) EKG 18
Four Year Old Child s ANS Response to 13 - Minute Protocol HR is an integrated measure vs. PEP (SNS) and RSA (PNS)
Six Children s RSA Responses to Protocol (3-5 years)
W. Thomas Boyce, MD MPH Pediatrician, Professor University of California, San Francisco; Pediatrics Boyce/ Alkon Psychobiology Laboratory (10 years) University of California, Berkeley; Psychology Nicki Bush, PhD Clinical Psychologist, Adjunct Professor University of California, San Francisco; Psychiatry Brenda Eskenazi, PhD Professor University of California, Berkeley; Public Health Center of Environmental Research and Children s Health(CERCH) Julianna Deardorff, PhD Assistant Professor University of California, Berkeley; Public Health Marilyn Essex, PhD Sociologist, Professor University of Wisconsin, Madison 22
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Ref: Boyce WT, Chesney M, Alkon A, et al. Psychobiologic reactivity to stress and childhood respiratory illnesses: Results of two prospective studies. J Psychosom Med 1995, 57:411-22. # of Resp. Illness/ 6 Months 5.0 4.5 Hi Blood Pressure (BP) Reactivity Low BP Reactivity 4.0 Low High Ecologic Child Care Stress 24
# of Resp. Illness/ 6 Months 5.0 4.5 Hi BP Reactivity Low BP Reactivity 4.0 Low High Ecologic Child Care Stress 25
Children with Sickle Cell Disease Oakland Children s Hospital Oakland, California References: Pearson S, Alkon A, Treadwell M, et al. (2005). Autonomic reactivity and disease severity in children with sickle cell disease. Clinical Autonomic Research. 15:400-407. Treadwell MJ, Alkon A, et al. (2010). Stress reactivity as a moderator of family stress, physical and mental health and functional impairment for children with sickle cell disease. Journal of Developmental and Behavioral Pediatrics. 31: 491-497. 26
An inherited condition that affects hemoglobin structure and function Results from a single base change on the beta globin gene of the red blood cell Produces misshapen beta subunits which misalign into rigid strands in the absence of oxygen; The rigid strand give the red blood cell a sickle shape Sickled cells have difficult flowing through blood vessels causing vaso-occlusion Complications include chronic anemia, susceptibility to infection, stroke, and most commonly pain. 27
To evaluate whether ANS reactivity modifies the relation between family stress, and physical and mental health, and functional impairment for children with sickle cell disease. 28
Pilot study: n = 19 4 to 9 year old children with sickle cell disease (SCD) Cohort study: n = 38 5 to 8 year olds with SCD Completed a 20 minute ANS protocol with continuous measures of heart rate, RSA and PEP Caregivers completed measures of family stress, child physical and mental health symptoms, injuries and functional impairment. 29
1.0.8 r = -.44, n=19, p<.05 Externalizing Behavior Symptoms.6.4.2 0.0 -.2-4 -2 0 2 4 6 8 r = -.44 PEP Difference Score 30
ANS Profile SNS PNS Coactivation + + Coinhibition - - Reciprocal parasympathetic activation Reciprocal sympathetic activation - + + - Reference: Berntson et al, 1991; Salomon, et al., 2000; Alkon, et al. 2003 * Based on difference scores; Neg. scores = sympathetic activation or parasympathetic withdrawal. 31
Injuries 1.0.8 RSA and PEP Reactive Classic Reactivity.6.4.2 Not Classic Reactivity 0 Low High Family Stress Note: Significant for the cognitive domain of ANS protocol. 32
Child Impairment.3 RSA and PEP Reactive Classic Reactivity.2 0 Not Classic Reactivity Low High Family Stress Note: Significant for the social domain of ANS protocol. 33
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Study Design: Cohort study of children from birth Data Collected (Birth to 9 years, N=120): Father present or not in child s 1st year of life Autonomic nervous system (ANS) reactivity at age 7 Blood pressure (mean arterial pressure = MAP) Mental Health/ Behavior at age 9: Symptom Severity includes teacher- and parent-ratings of children with both internalizing (e.g. shy, withdrawn) and externalizing (e.g. aggressive) behavior problems 3 5
Fathers Presence in the First Year of Life Makes a Difference Figure 4: Interaction of MAP Slope and Father Involvement Symptom Severity 1.2 1.0 0.8 0.6 0.4 0.2 0.0-0.2-0.4-0.6 Low Father Involvement Low Father Involvement High High MAP Slope Boyce, Essex, Alkon, et al. (2006). J Amer Academy of Child Adolescent Psychiatry. 45(12):1510-20. 36
CHAMACOS Center of Health Assessment of Mothers and Children of Salinas Center for Children s Environmental Health Research UC, Berkeley School of Public Health Brenda Eskenazi, PhD Director Abbey Alkon, PhD and W. Thomas Boyce, MD
Characteristics of Mothers (N=601) Mean age: 25 years 65% have more than one child 92% Spanish-speaking 85% born in Mexico; 54% < 5 years in U.S. 96% living within 200% of poverty level 44% 6 th grade education or less 44% worked in agriculture during pregnancy 84% other agricultural workers in household
Are the ANS responses to resting or challenging conditions stable from 6 to 60 months of age? Does adversity during the prenatal period affect children s ANS trajectories from 6 to 60 months of age? Does children s ANS reactivity at 5 years of age modify the relationship between adversity experienced in the first 5 years of life and children s aggression at 7 years of age?
Data Collection Times: Prenatal, 6 months, 1, 2, 3.5, 5, & 7 years Maternal interviews in Spanish or English, including family support, income, housing situation, work situation Height and Weight ANS Protocol at 6 months, 1, 3.5 and 5 years Home observations 40
Alkon A, Davis NV, Boyce WT, Eskenazi B. (2011). Developmental Changes in Autonomic Nervous System Resting and Reactivity Measures in Latino Children from Six to Sixty Months of Age. Journal of Developmental and Behavioral Pediatrics. 32:668-677. 41
Boys Girls Developmental Changes: HR decreases RSA and PEP increase Alkon et al. (2011). Journal of Developmental and Behavioral Pediatrics 42
There are developmental trends for HR, RSA and PEP from 6 to 60 months of age. Resting autonomic measures are moderately stable from 6 to 60 months. Reactivity measures are not stable in the first 5 years of life. 43
Does adversity during the prenatal period affect children s ANS trajectories from 6 to 60 months of age? Alkon, A et al. (2014) Prenatal adversities and Latino children s autonomic nervous system reactivity trajectories from 6 months to 5 years of age. PLOS ONE, 9(1). 44
Fetal programming is a process by which a stimulus or insult during a vulnerable developmental period has a long-lasting or permanent effect. (Davis, et al. (2001) Journal of Child Psychology and Psychiatry) Exposure to adverse conditions during pregnancy can alter the neurochemistry of the fetus central nervous system. Adversity experienced during sensitive periods of fetal development can program a fetus neurological development and affect their health later in life. 45
Family stress between infancy and 5 years of age is associated with increased sympathetic nervous system reactivity at 7 years of age. (Ellis, Essex et al. Devel and Psychopathology 2005) Socioeconomic adversities, such as poverty, have been associated with less ANS reactivity. (Evans & Kim (2007). Psychological Science) Alkon 2011 46
Cumulative (social support, socioeconomic) Social Support Adversity Mother is not living with father of baby (25%) Low social support (26%) Socioeconomic Adversity Household crowding (>=1.5 persons/room) (38%) Living at or below the U.S. poverty level (household income/ # persons in home) (62%) Family of 4 with an income of 22,600 USD is at the poverty level Alkon, A et al. (2014) Prenatal adversities and Latino children s autonomic nervous system reactivity trajectories from 6 months to 5 years of age. PLOS ONE, 9(1). Alkon 2011 47
Social Support Adversity Socioeconomic Adversity Children whose mothers had no adversities changed from low to high HR or PEP reactivity versus children whose mothers had one or two prenatal adversities. 48
There is no relationship between prenatal adversity and children s RSA reactivity. The relationship between prenatal adversity and children s ANS trajectories differ for HR and PEP reactivity. Alkon 2014 49
Young children growing up in families with mothers who have social support adversity and/or socioeconomic adversity show less physiologic plasticity than children growing up in families whose mothers experienced few or no prenatal adversity. Children whose mothers experienced no adversities showed more biologic sensitivity to their environment in the first 5 years of life. Alkon 2014 50
Alkon, A, Waters, S, Eskenazi, B, Harley, K, Boyce, WT (manuscript in preparation) Alkon 2011 51
The most common behavior problems for young children, ages 4 8 years old, are externalizing behavior problems. (Offord, et al., 2001). Externalizing behavior problems include acting out behaviors, aggression, and defiance. Children with persistent externalizing behavior problems have more academic and social problems during adolescence. (Kellam, et al., 1983, 1994).
Socioeconomic Household crowding Income and Number of people in household (poverty level) Social support Home environment Daily reading to child Meals with mother and child Housing quality Acculturation Language spoken at home Summary Index Dichotomize adversity variables at each age (0,1) Sum indices across ages (6,12, 24, 42, 60 mo.) Summary Index: mean 11.7 (3.8), range 1-21 Alkon 2011 53
Age: 7 years Measure: Behavioral Assessment System for Children (BASC): subscales: Aggression, Depression, Internalizing, Externalizing Informants: Teachers (survey) and mothers (interview) 54
Cum Index 6 months r (n) 1 year r (n) 2 years r (n) 1 year.55 -- -- -- 3.5 years 2 years.45.51 -- -- 3.5 years.46.40.47 -- 5 years.38.39.50 mean(sd), n 3.1(1.3) 2.9(1.3) 2.8(1.2) 2.6 (1.3) Alkon 2011 55
ANS Profile PEP Difference RSA Difference Frequency (%) Coactivation Negative Positive 52 (20%) Coinhibition Positive Negative 72 (27%) SNS inhibition/ PNS activation SNS activation/ PNS inhibition Positive Positive 40 (15%) Negative Negative 100 (38%) Coinhibition: Parasympathetic withdrawal under challenging conditions compared to rest; No sympathetic activation 56
Cumulative Adversity Birth to 5 Years Aggression, Depression Age 7 PEP & RSA Reactivity or ANS Profiles Age 5 Covariates: Prenatal BPA, maternal depression at 12 mo., years in US at time of pregnancy, child sex, child age at ANS 57
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There were no significant interactions between cumulative adversity and RSA or PEP reactivity predicting parent- or teacher- reported child mental health problems. There were significant interactions between cumulative adversity and children with the coinhibition ANS profile to predict parentreported child depression and aggression, but not internalizing, externalizing. 59
4.5 Parent-Rated Aggression 4 3.5 3 2.5 Coinhibition No Coinhibition 2 Low Adversity High Adversity 60
4.5 Parent-Rated Aggression 4 3.5 3 2.5 2 1.5 1 Low household density High household density Coinhibition No Coinhibition 61
6 Parent-Rated Aggression 5.5 5 4.5 4 3.5 3 2.5 Coinhibition No Coinhibition 2 Daily reading No daily reading 62
Young children growing up with multiple adversities who respond to challenge with parasympathetic withdrawal and no sympathetic activation are more likely to have aggression at age 7 than children with other ANS profiles. This pattern does not hold for SNS or PNS alone, only when modeled together. 63
Young children need emotional support from adults, especially for children who are growing up in poor families whose mothers lack social support. Adversities experienced early in life get under the skin and may impact the life course of adolescents and adults. Alkon 2011 64
Reading Rhyming Routines Rewards Relationships 65
There are sensitive periods during a child s development which affect their autonomic nervous system. There are individual differences in how children physiologically respond to their environment. Children s trajectory in life can be influenced by their positive or negative environmental experiences. 66