1. Early Experience, Stress and Neurobehavioral Development Center NIMH Interdisciplinary Development Science Center

2.  How do early life events get “under the skin” to impact long-term mental and physical health outcomes?  Understanding the mechanisms should facilitate: ◦ Identifying targets for intervention/prevention efforts  Who is most vulnerable  Conditions to target  Sensitive Periods ◦ Assessing effectiveness of intervention/prevention efforts

3. Acute - enhances immune, Memory, energy replenishment, Cardiovascular function Chronic - suppresses immune, Memory, promotes bone Mineral loss, muscle wasting; Metabolic syndrome

4. Summary of CRF Functions  Reproduction  Slow Wave Sleep  Eating  Self Grooming  Despair  Neophobia [novel environ]  Hyperlocomotion [familiar environ]  Kindling  LC unit activity sBlood Pressure sHeart Rate sBlood Sugar  GI Blood Flow sGluconeogenesis sLipolysis sProteolysis sInsulin Resistance  Inflammation Immune Function Catecholamines Glucocorticoids ACTH STRESS

5. CORT Levels Increasing---> Negative………………Positive Goldilock’s Principle: Inverted U Relationships With Health Promoting/Threatening Effects Promotive EffectsSuppressive Effects

6. Diurnal Cortisol Rhythm

7. Maternal Care in Rodents Adult Outcomes of Poor Maternal Care  Low Maternal Care ◦ Higher and more prolonged CORT responses in adulthood ◦ Higher CRF activity ◦ Higher brain NE activity ◦ Less Brain production of stress modulators: e.g natural opiates ◦ More fearful/anxious behavior ◦ Poorer memory; effects on learning/memory systems

8.  Epigenesis: Silencing of genes in particular tissues ◦ methylation and histone acetylation; ◦ gene cannot interact with its environment ◦ can’t transcribe code for its protein  Low Maternal Care Reduced expression of  GR gene involved in regulating CORT (Meaney and Szyf)  BDNF gene in PFC (Roth/Sweatt)  Estrogen Receptor Gene (Champagne)  Rats Only? ◦ Adult suicide victims: stress-regulating gene silencing in same brain region as rodent studies IF suicide+child abuse; not suicide w/o child abuse

9.  Does parental care buffer stress biology early in life?  Are neglect and abuse associated with atypical patterns of stress hormone production and regulation?  Is a signature of ELS observed among adults with these experiences?  Do interventions that foster better behavioral adaptation shift functioning of the CORT system?

10. Percent of Children Atypical Patterns Soon After Placement Toddlers and Preschoolers Adoption Foster: Dozier Foster: Fisher

11. Early Abuse + Anxious/Depressive Symptoms 7-12 Year Old Children Cicchetti, Rogosch and Gunnar, 2009

12.  First 3 months of life: CORT production and regulation is extremely sensitive to variations in parental care  Blair et al: Thousand low income babies: maternal behavior at 7 mos trumps income/needs ratio in predicting CORT reactivity at 7 months and in predicting 15 months CORT regulation and Attention.  By 2 nd year of life: infants in secure attachment relationships show no increase in CORT when frightened/distress; insecure do and attachment disordered infant have chronic high CORT.

13.  Number of studies now (Heim, Carpenter, Elzinga)  Adults with Depression+Early Abuse/Neglect: Hyper-Activity  Adults with No Depression+Early Abuse/Neglect: Hypo-Activity

14.  Dozier: Attachment and Biobehavioral Catch- up Intervention with Infants in Foster Care  Train foster parents to support the attachment and regulatory needs of neglected/abused infants and toddlers  Proof of principle study ◦ Infants/Toddlers in Foster Care  Randomized to Treatment and Control ◦ Comparison Group of Same Low SES

15. Salivary Cortisol Levels Dozier, M et al., 2006, Journal of Social Issues, 62, 767-785.

16.  Fisher: Multi-dimensional Treatment Program ◦ Training Foster Parents to Manage Behavior Problems in supportive, consistent fashion ◦ 24/7 support line for foster parents ◦ Maintaining Consistency of Care and Plan for Transitions  Tracking Diurnal Cortisol Rhythm; focus on amelioration and/or prevention of disruption on normal daily pattern

17. 1 mo post placement12 mo post placement Fisher, P. A.(2007). Psychoneuroendocrinology, 32, 892-905.

18.  How does early life stress “get under the skin” to affect life-long health? ◦ HPA axis may provide one mechanism ◦ Gene by Experience Effects Likely ◦ Experience and epigentic processes  Measures of stress neurobiology sensitive to early intervention