Assessing the biological stress system: considerations for family research. Darlene A. Kertes,, Ph.D. University of Florida

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1 Assessing the biological stress system: considerations for family research Darlene A. Kertes,, Ph.D. University of Florida

2 Genes Specific genes Genetically-influenced traits Environment Distal: Rearing Proximal: Life stressors Biological Processes Biological Stress Response Neurotransmitter Activity Neural Circuits Poor Outcomes Emotional Problems Behavior Problems Health Problems

3 Overview Relevance of the HPA system Early care effects on stress system activity Methodological issues in biological stress research The case for multi-level level research

4 Relevance Why should you care about the biological stress response system? Affects nearly every organ system, impacts on cognition, memory, emotion, behavior, health Mechanism by which prior experiences impact response to future life events

5 Functions of Stress Physiology

6 Functions of Stress Physiology Immediate Challenge Regulatory Function

7 Functions of Stress Physiology Immediate Challenge Regulatory Function Allostasis

8 Stress system activity essential for life & to meet challenges... Circadian rhythms Neurons responsive to NTs Liberate glucose Enhance amino acid production Repeated/chronic elevations: Growth Immune function Memory and attentional processes Fear circuits

9 HPA axis alterations observed in disorders b b b b b b b b b b b b Addiction Depression & anxiety disorders Cardiovascular disease Alzheimer s Asthma Immunogenic cancers Infectious diseases Obesity Diabetes Gastric disorders Would healing & general immune function And more

10 Image: Adinoff et al. (1998)

11 Life experience affects gene expression via cortisol

12 Family effects on cortisol Relationship quality Spouses/romantic partners Parent-child conflict Early attachment/ parenting quality Life stress Parental depression Family stress Poverty Child care and maltreatment Abuse Neglect Orphanage care Day care quality Familial risk Relatives of depressed or addicted individuals

13 Overview Overview of the HPA system Early care effects on stress system activity Basal activity & stress reactivity Early adversity & typically developing Methodological issues in biological stress research The case for multi-level level research

14 Effects of early experience Do early experiences in close relationships with caregivers alter the development of the HPA axis? Extreme adversity/ Deprivation of relationships with caregivers Typical variation in parenting quality

15 Long-term effects of early adversity on basal cortisol levels Participants Internationally adopted children aged Adopted birth- 8 yrs With adoptive families >3yrs Key measures Parent-reported reported pre-adoption conditions Linear growth delay Basal cortisol (wake-up & bedtime)

16 Linear growth delay as indicator of early adversity/relationship disruption b Psychosocial Dwarfism / Short Stature Impact on growth of bone (long bones, skull) Weight appropriate for height

17 Deprived Care Linear Growth Delay Wakeup Cortisol Diurnal Decline in Cortisol Deprived care (adoptive parent report): Age at adoption Institutionalization Pre-adoption neglect & abuse

18 AM cortisol levels higher for growth delayed children Salivary Cortisol µg/dl Wakeup Typical AM level Bedtime Smallest 25% Biggest 25% Kertes et al (2008) Development and Psychopathology

19 Effects of early experience Do early experiences in close relationships with caregivers alter the development of the HPA axis? Deprivation of close, supportive relationships with caregivers Typical variation in caregiver quality

20 Parental buffering of temperamental vulnerability to stress response Assn of behavioral fear/inhibition - cortisol reactivity in early childhood (4 yrs) General or stressor-specific? specific? Parenting quality (behavioral observation): Buffer/exacerbate temperamental vulnerability to stress at bio level?

21 Socially inhibited children show cortisol response to social stressor Cortisol change in µg/dl * Exuberant Average Inhibited Social Inhibition Kertes et al. (2009) Developmental Psychobiology

22 High parenting quality buffers cortisol responses for socially inhibited children Cortisol change in µg/dl Exuberant Average Inhibited Social Inhibition * High quality Low quality Kertes et al. (2009) Developmental Psychobiology

23 Overview Overview of the HPA system Early care effects on stress system activity Methodological issues in biological stress research The case for multi-level level research

24 Targeted paradigms & research questions (detecting effects) Paradigms that provoke stress response* Diverse methods used in children Ethical limitations mild stressors Strategies Develop standard protocols for children Focus on subgroups of responders in particular contexts *Dickerson & Kemeny (2004); Gunnar et al., (2008)

25 No evidence for general biological stress response Salivary Cortisol µg/dl T1 T2 T3 Kertes et al. (2009) Developmental Psychobiology

26 Socially inhibited children show cortisol response to social stressor Cortisol change in µg/dl * Exuberant Average Inhibited Social Inhibition Kertes et al. (2009) Developmental Psychobiology

27 Multiple factors influence stress system Target psychosocial variable & Digestion, sleep, exercise Systemic stressors (inflammation, pain) Caffeine, alcohol, tobacco Endogenously regulated basal activity Other perceived/actual psychosocial stressors Strategy 1: Data collection constraints Strategy 2: Identify trait cortisol

28 School-aged children: bedtime cortisol affected by after-school activities Salivary cortisol in µg/dl Girls Boys Unscheduled Active Kertes & Gunnar (2004) Child Development

29 Basal cortisol among internationally-adopted adopted children children 0.9 Salivary Cortisol µg/dl Wakeup Bedtime Growth delayed Non-delayed Kertes et al. (2008) Development and Psychopathology

30 Identifying trait cortisol error 11 error 12 error 21 error 22 error 31 error 32 Day 1 Sample 1 Day 1 Sample 2 Day 2 Sample 1 Day 2 Sample 2 Day 3 Sample 1 Day 3 Sample 2 Day 1 Day 2 Day 3 State Cortisol 1 State Cortisol 2 State Cortisol 3 Trait Cortisol Kertes & van Dulmen (in preparation)

31 Cortisol due to trait, state, and error Variance Explained 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Day 1 Day 2 Day 3 Error State Trait 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Day 1 Day 2 Day 3 Error State Trait AM PM Kertes & Van Dulmen (in preparation)

32 Methodological considerations: HPA axis acts/interacts with other systems HPA axis SAM system Immune function Sleep/circadian cycles Other steroid hormones Peptides Neural activity (Other biomarkers of potential interest)

33 Assessing multiple levels of analysis Behavioral & biological stress measures Often uncorrelated Update/standardize behavioral measures* Intervening factors Provide different information Exposure & response Objective & subjective Differentiate from systemic stressors *Monroe (2008) Helhammer et al. (2009); Jessop & Turner-Cobb (2008)

34 Multi-directional effects in development Environmental Demands (physical, social, cultural) Behavior Surface (emot. regulation, coping, flight-fight) Fast Acting Physio Processes (neural, HPA, ANS activity) Slow Acting Physio Processes (genetic activity) Individual development Gottlieb (1996)

35 Assessing multiple levels of analysis Multiple modes of transmission Routes of transmission for family effects Epigenetic Genetic (or G x E) Cultural (socialization) Strategy: Interdisciplinary research via collaboration/ cross-training Photo: D. Sharon Pruitt

36 Challenges to integration Pragmatic Methodological Investment in phenotyping vs. sample size Analysis

37 Genetic research on familial stress-related related disorders Major Depression and Alcohol Dependence Family risks & other life stress Stress biology system implicated Neurobiology-guided guided gene selection

38 Genetic studies can identify best candidates Number of Depressive Symptoms Corticotropin-releasing hormone binding protein CC CA AA Genotype Mu-opioid receptor CC CT TT Genotype Kertes et al. (submitted)

39 to examine multiple modes of transmission for familial stress-related related disorders Gene-environment environment interplay in the Child Development Project Early life family stress Adolescence experiences Types of research questions Basic science Preventive intervention Multi-level level research?

40 Biological stress system in family research: Take home points Mechanism by which family experiences impact response to future life events & emotional/physical health Family experiences impact stress system activity Implementation requires careful methodology to detect effects Behavioral & biological complementary, not redundant Family effects transmitted via social, biological, genetic paths

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