A neurobiological approach to early medical trauma. Stacy S Drury, M.D., Ph.D. Child and Adolescent Psychiatry Tulane University

Transcription

1 A neurobiological approach to early medical trauma Stacy S Drury, M.D., Ph.D. Child and Adolescent Psychiatry Tulane University

2 A critical research gap 50% of healthcare utilized by children less than five years of age Clear evidence that early stress results in changes to CNS/cortisol/neurotransmitters Children under 6 are different Cognitive Emotional Social Neurobiological

3 Medical Illness disrupts normal development

4 Take home points Early adversity and trauma impact the brain Effects underlying neural circuits Attention Arousal Memory Threat perception Early identification and treatment can alter negative neurobiological trajectoriesonue to the rapid brain development during this time Developmentally sensitive evidence base

5 Outline The Biology to Medical traumatic stress Introduction to neurodevelopment Lasting impact of early stress across domains Medical traumatic stress

6 Brain development From conception through adult Different parts of the brain develop at different rates Experience dependent Impact of trauma and stress differs depending on developmental timepoint

7

8 Synaptogenesis and Pruning Connections between neurons Initial overproduction of synapses then pruning back based on use/experience Visual cortex Synaptogenesis peak at 4 th postnatal month Pruning throughout preschool Auditory cortex Synaptogenesis peak around 4 th postnatal month Pruning into middle childhood Prefrontal cortex Synaptogenesis: completed until 1 year Pruning continues into young adult

9 Myelination- more efficient Myelin function Insulation of neurons Speeds up neural connections Experience dependent Sensory/motor regions myelinate first Frontal cortex: last to develop

10 Outline The Biology to Medical traumatic stress Introduction to neurodevelopment Lasting impact of early stress across domains Medical traumatic stress

11 Negative Outcomes across domains Increased negative outcomes: Mental illness, substance abuse Poor school/work performance Decreased cognitive and language (Nelson et al 2007) Altered threat perception (Pine et al 2005) Stress alters underlying neurobiology cellular migration Apoptosis- neuron cell death Synaptogeneis Strengthening of neural circuits

12 Adverse Childhood Events study

13 Cumulative stressful life events 60% 50% 40% 30% 20% 10% 0% or more Low magnitude High magnitude

14 Cumulative stressors and psychiatric disorders

15 Empirical studies: Impact of negative life experiences Preclinical/animal models Mouse models Maternal separation Variable foraging Primate models Peer rearing Variable foraging * Reviewed in Stevens et al 2009

16 Empirical studies: Impact of negative life experiences Medical trauma Abuse/neglect Chronic Illness Single incident trauma Disaster exposure- hurricane, wars Institutional rearing Severe social deprivation

17 Across studies Lasting impact on range of outcomes dose effect Earlier exposure increased impact Developmental differences Modified by caregiving Key importance of early caregiver Attachment go to person

18 Bucharest Early Intervention Project

19 Institutional care 8,000,000 children being raised in institutions Most common form of care for orphaned and abandoned young children Limited connection with a primary caregiver Regimented life Limited direct personal attention for needs

20 Comprehensive assessments at 30, 42, 54 months, 8 and 12 years Study design Institutional Group NIG n=72 CAUG n=68 FCG n=68

21 Differences between institutionalized and community children Caregiving quality Height, weight IQ Expressive/receptive language Competence Psychiatric disorders Attachment Stereotypies Expression of positive emotion Recognition of facial expression of emotion Brian electrical function EEG/ERP

22 Main effects of intervention

23 Positive effects of intervention IQ Expressive and receptive language Height and weight Stereotypies Internalizing disorders Expression of positive emotions Attachment Brain electrical activity- ERP, EEG Epigenetic changes

24 Intervention effects on expression of positive emotion Standardized Lab-Tab Score CAUG FCG months 42 months

25 Psychiatric morbidity

26 Rates of Psychiatric Disorders CAUG FCG NIG DECS Any axis I disorder Emotional disorders Behavioral disorders 61.5% 45.8% 22.0% 16.2% 44.2% 22.0% 13.6% 10.5% 30.2% 25.4% 6.8% 9.0% **Gender and birth weight significant moderators of intervention.

27 Timing matters Impact on cognition and language

28 WIPPSI FS IQ scores at 42 and 54 months Institutionalized Foster care Community months 54 months

29 IQ IQ of FCG and CAUG at follow-up by age of placement IG Before 24 mo IG After 24 mo FCG Before 24 mo FCG After 24 mo mo 42 mo 54 mo

30 Language at 42 months

31 Brain Function: EEGs

32 Distribution of Alpha Power C Across the Scalp CAUG FCG > μV 2 FCG < 24 NIG 2.44μV 2

33 Even at the cellular level

34

35 Outline The Biology to Medical traumatic stress Introduction to neurodevelopment Lasting impact of early stress across domains Medical traumatic stress

36 Medical trauma Few studies have looked at children less than 6 years old using developmentally specific models Cancer/Medical Illness PTSS and PTSD in parents 50% of mothers had symptoms of PTSS 28% met criteria for PTSD PTSD not directly related to severity of medical treatment Longitudinal studies: Stuber et al 2010 No increased rates initially but Elevation of PTSD and PTSS in young adult cancer survivors Increased risk for PTSD in young adulthood if <4yo +XRT

37 Preschool age medical studies: Stoddard et al months burns 29% acute stress symptoms Meyer et al years after burns age 2-3 CBCL elevated depressive, sleep and somatic scores De Young et al 2012: PTSD n=130 Age 1-6 accidental burns 35% diagnosed with one psychological disorder Comorbid with PTSD Persistent over 6 months Curtis and Luby 2008 : Medically Ill preschool Elevated depression Meiser-Stedman 2008 n=114 age 2-10 years, MVA 11.5% dx and 13.9% at six months with PTSD using alternative algorithm

38 Trauma exposure 284 preschool children in New Orleans 44% had PTSD No difference in dx or symptom number between trauma groups (c 2 =2.069, df 2 p=0.3554) Single incident medical trauma 38% Domestic Violence 42% Hurricane Katrina 48%

39 PTSD Criteria A: exposure Criteria B: re-experiencing Criteria C: avoidance Criteria D: hyper-arousal Restricted range of emotions Marked diminished interest Irritability or outbursts difficulty concentrating Exaggerated startle

40 The natural history of PTSD is persistence

41 Sleep problems Family stress Anxiety Attention problems ADHD PTSD Hearing/learning disability worry

42 Looking at a pediatric setting N=69 (43 boys, 26 girls); mean age 36 months Recruited from hospital based primary care clinic Majority on public health insurance Medical Event, no procedure E.g. Hospital visit, no blood draw, IV Medical event, procedure E.g. Included blood draw, IV, stitches, surgery

43 Life Events Frequency

44 Type of Trauma and Clinical Signs of PTSD

45 PTSD Symptoms with Medical Events

46 Vulnerability factors History Previous experiences with medical care Perception of threat/treatment intensity Other traumatic experiences Biology Genetic vulnerability Physiological reactivity Family history of anxiety, PTSD, trauma

47 Scott 4 year old AA male Referred to MD for ADHD- we think it is because of his liver transplant, maybe it did something to his developing brain. Fighting in school Runs around the classroom all the time Can t sit still

48 Additional history Acute hepatic failure at 30 months of age Life flighted with parents Dad arrested in hospital for threatening staff during pre-transplant workup previously healthy child Parents with unstable relationship

49 That tube was in my throat

50 Scott s version Look, can I show you my stomach? The surgeons cut me open like a turkey. No my liver wasn t the badest thing that happened. When those police took my Dad that made me the madest when I see them I am gonna beat them up.

51 Scott s version continued If I don t take my medicine I am gonna die I remember everyone crying in my room in Texas, they kept saying I was dying. I don t like it when my mom cries

52 Maternal report Scott wakes me up and says Mommy I have to take my medicine if I don t I will die, time to get up He won t leave my side, he is always checking on me

53 Putting it all together Cumulative Stress exposure important Trauma does not happen at random Early intervention can prevent alteration of neurodevelopmental trajectory Evidence based treatments exist Importance of goto-person

54 Bronfenbrenner s Ecological Theory Macrosystem Exosystem Family Microsystem School Microsystem Peer Microsystem Neighborhood Microsystem

55 Questions?

56 Bucharest Early Intervention Project Principal Investigators Charles A. Nelson, Ph.D.*, Harvard University Nathan Fox, Ph.D.*, University of Maryland Charles H. Zeanah, M.D. Tulane Collaborators/Contributors Anna Smyke, Ph.D. Mary Margaret Gleason, M.D. Valerie Wajda Johnston, Ph.D. Julie Larrieu, Ph.D. Administration/Management Elizabeth Furtado Romanian Research Team Anca Radulescu, Nadia Radu, Carmen Pascu, Iuliana Dobre, Nicoleta Corlan, Veronica Ivascanu, Florin Tibu, Amelia Nistor

57 Resources