Sue Stephenson MD Sonoma County ACEs Connection May 30 2017 GOALS Understand science and concepts behind ACEs and resilience Relate neuroscience to traumainformed care Develop language to receive and discuss new information and apply new studies ID: 632257
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NEUROBIOLOGY OF ACEs
and resilience
Sue Stephenson, MD
Sonoma County ACEs Connection
May 30, 2017Slide3
GOALS
Understand science and concepts behind ACEs and resilience
Relate neuroscience to trauma-informed care
Develop language to receive and discuss new information and apply new studiesSlide4
OUTLINE
Define trauma and resilience
How it works:
The blueprint (genes) and storehouse (chromosomes)
The directors and building blocks: genes to proteins
Changing the blueprint readout: epigenetics
Hard-wire: Brain and other nerves, autonomic nervous system
HPA axis
Liquid: hormones/hormone-like molecules
Big picture: putting it togetherSlide5
The field of neuroscience is so new,
we must be comfortable not only
venturing into the unknown
but into error.
- Richard
Mendius
, M.D. Slide6
WHAT IS TRAUMA?Slide7
What is Resilience?
Capacities innate in the brain and body
Hard-wired in by evolution and experience
genetic, epigenetic, developmental, psychosocial, and neurochemical factors
Encoded in neural circuitry, hormonal and metabolic aspects of the body
Learned in responses to experiences and interactions and can be modified life-long
Pre-frontal cortex is CEO of resilienceSlide8
BIG PICTUERE:
everything is relatedSlide9
How does trauma increase disease risk?
Habits and lifestyle
Neural firing or lack thereof
Epigenetics
Inflammatory molecules
Hormonal/neurochemical effectsSlide10
How is resilience increased?
Habits and lifestyle
Neural firing or lack thereof
Epigenetics
inflammatory molecules
Hormonal/neurochemical effects
Safety, diet, sleep, exercise, positive relationship, trust, humor/laughter, sense of controlSlide11Slide12Slide13
RATES OF ADAPTATION
SLOW: genetic, evolution
INTERMEDIATE: inherited epigenetic
“IMMEDIATE”:
epigenetic, change nerve pathways
changes in brain structure: new nerves or nerve pathways
PFC/cortex more “plastic”
Some genetic variations are adaptive for the group as a whole Slide14
Genetics
Epigenetics, nerves and nerve pathways, hormonal/neurotransmitter patterns
Infinite variability and combinationsSlide15
Genetics: how it works
Cell
Nucleus
Chromosomes
DNA: “blueprints”
Gene: mutations, SNP’s, polymorphisms
Reading the blueprints
Proteins and protein-like molecules (building blocks, messengers, instructors)Slide16Slide17Slide18
Making a protein from DNA: transcriptionSlide19
“
I don’t blame you for everything. I blame Dad for some things, too”Slide20
The telomere storySlide21Slide22Slide23
EpigeneticsSlide24Slide25
Factors affecting epigenetic modification of DNA (most are life-long)
Relationships
Environment
Developmental periods
Environmental chemicals
Drugs/pharmaceuticals
Diet
Exercise
Stress
Sleep or lack thereof
Attitude, sense of control, “stress inoculation”Slide26
How do epigenetic changes go from one generation to the next, and which ones do that?
Most epigenetic changes are erased as a reproductive cell (egg or sperm) is formed. A few persist, and we don’t know how or why this happens.Slide27Slide28
January 1998: Project Ice StormSlide29
Project Ice Storm
was designed to study the effects of in utero exposure to varying levels of prenatal maternal stress (PNMS), resulting from an independent stressor on the children's development from birth through childhood. In January 1998, the Quebec Ice Storm left millions of people without electricity for up to 40 days. In
Project Ice Storm
we were able to separate the "objective" stressors (days without power) from the "subjective" reactions (post-traumatic stress symptoms) and physiological reactions (cortisol over 24 hours), and maternal personality factors of 178 pregnant women exposed to the disaster. Child follow-ups at ages 6 months, and 2, 4, 5.5 and 6.5 years show significant effects of objective and subjective PNMS on temperament, parent- and teacher-rated behavior problems, motor development, physical development, and IQ, attention, and language development. The majority of these effects persist at our most recent assessments.
https://www.mcgill.ca/projetverglas/icestormSlide30
How the body adjusts: Hard-wire and liquid
Nerves, brain
neurotransmitters
Hormones, cytokines,
catecholaminesSlide31
Hardwire: neuroscienceSlide32
Modern neuroscience
What neural structures/circuits are
How neural structures/circuits develop
How the brain functions: processes information and communicates with itself and body
How brain learns/installs patterns of coping
How brain rewires its memory patterns
By necessity also involves related functions, like epigenetics and hormonesSlide33
Limbic brainSlide34
Prefrontal cortexSlide35
Prefrontal cortex (PFC)
Executive center of higher brain
Evolved most recently – makes us human
Development kindled in relationships
Matures the latest – 25 years of age
May not engage when lower areas of brain are on alert: slower to respond
CEO of resilienceSlide36
Functions of Pre-Frontal Cortex
CEO of Resilience
Regulate body and nervous system
Quell fear response of amygdala
Manage emotions
Attunement – felt sense of feelings
Empathy – making sense of experience
Insight and self-knowing
Response flexibility
Planning, decision making
Morality Slide37
“Dynamic Neural Activity during Stress Signals Resilient Coping”) of human volunteers, published in PNAS, scientists led by
Rajita
Sinha, Ph.D., and
Dongju
Seo
, Ph.D., Slide38
What is the brain made of?
Nerve cells and supportive stuffSlide39
SynapseSlide40
NEUROPLASTICITY
Greatest discovery of modern neuroscience
Growing new dendrites and neurons
Strengthening synaptic connections
Myelinating pathways – faster processing
Creating and altering brain structure and circuitry “fire together, wire together”
Organizing and re-organizing functions of brain structures
The brain changes itself - lifelongSlide41Slide42
Conditions that Activate
and Guide Neuroplasticity for
Resilience
Safety
Positive Relationships
Positive Emotions
Novelty, Challenge
Little and Often
Small challenges successfully met (“stress
innoculation
”)Slide43
Positive Relationships
Attunement - “felt sense”, non-verbal
Empathy – making sense of story, verbal
Acceptance – it’s all understandable, it’s all workable
No shame or blame – biggest
derailers
of resilienceSlide44
Practices to Accelerate Brain Change
Presence – primes receptivity of brain
Intention/choice – activates plasticity
Practice – “little and often” installs change
Perseverance - creates new pathways, new more resilient habits of coping
Slide45
Neurotransmitters and moodSlide46
Autonomic nervous system
Homeostasis
Gets information/instruction from hypothalamus
Sympathetic
Mobilize – act, create, play
Over-mobilize – fight-flight-freeze
Chronic – anxiety, stress
Balanced
Calm and relaxed, engaged and alert
Parasympathetic
De-mobilize – calm, rest
Over de-mobilize – shut down, numb out
Chronic – depression, dissociation
Controlled breathing stimulates parasympathetic-calmSlide47
HPA axis: how is cortisol made and regulated?Slide48
LIQUID: Hormones,
catecholamines
, cytokines
ADRENALINE (epinephrine), NOREPINEPHRINE
Immediate
CORTISOL
Takes a little longer, lasts a little longer
OXYTOCIN: hormone of safety and trust
Touch
Direct and immediate antidote to stress hormone cortisol; repairs damage from cortisol
CYTOKINES:
Inflammatory or protective:
Can be released by cells that are epigenetically changed in traumatic youthSlide49
Allostatic load: wear and tear on the body as it strives to maintain equilibrium:Slide50Slide51
Resilience future: personalized
Because of our understanding of neurosciences of trauma and resilience, we may/should be able to determine in the future which treatments/environments will work for which people, based on their individual genes, brain circuits, neurotransmitters, and hormone levels.
In the meantime we can be sensitive to possible changes caused by trauma, and realize that because of the ways our bodies and nervous systems are programed, small and gradual individualized interventions may work bestSlide52
Take home:
Understanding stress/trauma effects in the body help us be aware of a person’s possible physiology and sensitive areas
Importance of relationship on all levels: world, society, community, family, interpersonal
Everything is adaptive: understand this first to unpack trauma effects and gradually help shift to be adaptive to current environment
Physiologic powerful networks allow understanding of effects of trauma, and also play, touch, humor, meditation, positive thoughts, breathing, etc.Slide53
Resilience formula
Breathe
Laugh
Shift thought pattern
Meditate
Relate
Play
Exercise
Eat well
Touch Slide54
references
“A General Theory of Love”
Gabor Mate: books and
youtube
videos
The Body Keeps the Score: Brain, Mind and Body in the Healing of Trauma
, by Bessel Van der Kolk
Bouncing Back, Linda Graham, MFT
Steven
Porges
polyvagal theorySlide55Slide56Slide57
How long is your body’s DNA STRUNG END-TO-END?
A) 50 miles
B) 500 miles
C) 500,000 miles
D)Slide58
Resilience IMPORTANT STATEMENT HERE
Definition: Resilience is a capacity – innate in the brain – to “bounce back” from difficulty. To face the challenges and crises of our lives skillfully and flexibly, to navigate the twists and turns of ordinary human life and come back to our center so that we can cope. Linda Graham “Bouncing Back”
Resilience is defined as an ability to recover from or adjust easily to
genetic, epigenetic, developmental, psychosocial, and neurochemical factors misfortune or change.
May/should be able to determine in the future which treatments/environments will work for which people, based on their hormonal make-up and genes and neurotransmitters (fMRI,
etc
)Slide59
Neuroscience of Attachment
Secure attachment
Healthy brain, stable and flexible, open to learning
Insecure-Avoidant
Neural cement; closed to learning
Insecure-Anxious
Neural swamp; learning doesn’t stick
Disorganized
Dis-
integraton
; no learning
Multi-generational
“Good enough” parentingSlide60
pruningSlide61
Neuroscience of Attachment
Interpersonal neurobiology – Dan Siegel
Brain is a social organ
Develops best in interactions with other brains
Early on, develops only in interactions with other brains
Attachment shapes maturation of pre-frontal cortex, center of executive functioningSlide62Slide63
| Network-level differences in hypothalamic–pituitary–adrenal (HPA) responses to stress are evident in post-traumatic stress disorder (PTSD). The increased secretion of corticotropin-releasing hormone from the hypothalamus in PTSD is represented by a thick black line. The decreased adrenal release of cortisol in PTSD is represented by the thin black line. The increased negative feedback inhibition of the HPA axis by cortisol in PTSD is represented by thick red lines.
b
| Key molecular factors affecting genomic sensitivity to glucocorticoid
signalling
are shown. Cortisol binds to the glucocorticoid receptor (GR) in the cytoplasm, which is coded by nuclear receptor subfamily 3 group C member 1 (
NR3C1
). The glucocorticoid–GR complex is further bound by chaperone proteins that include FK506-binding protein 5 (FKBP5). Genetic variation of
NR3C1
and
FKBP5
are implicated in functional differences in glucocorticoid
signalling
in PTSD. The chaperone-bound glucocorticoid–GR complex is translocated into the nucleus and binds to glucocorticoid response elements (GRE), which ultimately affects transcription of a large number of genes.
c
| Several systems are affected by differential glucocorticoid
signalling
, including the brain, cardiometabolic sites, reproductive organs and the immune system. HSP90, heat shock protein 90. Part
a
adapted with permission from Ref.
32
, Massachusetts Medical Society.
Full size imageSlide64
Rogue slide
Figure 2. Psychological stress-activated signaling pathways in dentate gyrus granule neurons driving epigenetic modifications underlying induction of gene transcription and the consolidation of behavioral responses and memory formation.
Psychological stress evokes the concomitant activation of the GR and NMDAR-ERK-MAPK pathways. The concomitant activation of ERK1/2 and GR and their subsequent physical interaction facilitates the ability of pERK1/2 to phosphorylate MSK1/2 and Elk-1. Activation of these nuclear kinases results in the phosphorylation and acetylation of histone H3 (H3S10p-K14ac), which drives chromatin remodeling thereby allowing the gene transcription of IEGs like c-
fos
, egr1, and many other genes. The induction of gene transcription is critical for the consolidation of memory formation associated with the endured event. See text for references of studies supporting this concept. FS, forced swimming; Nov., novelty exposure; MWM, Morris water maze training; FC, contextual fear conditioning.Slide65Slide66Slide67
Figure 2.
Previous figure
|
Figure and tables index
Schematic model of the induction of immunological memory. (
a
) Time course of induction of immunological memory following pathogen exposure and clearance of infection. Entry of an infectious agent activates an innate response and antigen presentation. Once antigen levels exceed the threshold dose, the adaptive immune system is activated. Activated T cells secrete effector molecules that orchestrate the clearance of the infectious agent. At this stage, immunological memory also starts to form. (
b
) Time course of a protective immune response following exposure to mental stress. The stressful experience activates the hypothalamic–pituitary–adrenal (HPA) axis, the sympathetic autonomous system, as well as other cognitive processes that orchestrate the immediate response to stress (fight or flight). The stress hormones induce the mobilization of immune cells to the central nervous system (CNS), where they are activated by local antigen presenting cells. In the CNS, the activated cells secrete and regulate neurotrophic factors that maintain homeostasis, while building the immunological repertoire.Slide68
Fig. 1. Stress and the immune and neuroendocrine systems. CRH, corticotropin-releasing hormone. ( From Miller HM,
Maletic
V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.
Biol
Psychiatry 2009;65:732– 41; with permission.) Slide69Slide70
Schematic model of the induction of immunological memory. (
a
) Time course of induction of immunological memory following pathogen exposure and clearance of infection. Entry of an infectious agent activates an innate response and antigen presentation. Once antigen levels exceed the threshold dose, the adaptive immune system is activated. Activated T cells secrete effector molecules that orchestrate the clearance of the infectious agent. At this stage, immunological memory also starts to form. (
b
) Time course of a protective immune response following exposure to mental stress. The stressful experience activates the hypothalamic–pituitary–adrenal (HPA) axis, the sympathetic autonomous system, as well as other cognitive processes that orchestrate the immediate response to stress (fight or flight). The stress hormones induce the mobilization of immune cells to the central nervous system (CNS), where they are activated by local antigen presenting cells. In the CNS, the activated cells secrete and regulate neurotrophic factors that maintain homeostasis, while building the immunological repertoire.Slide71
Functions of Pre-Frontal Cortex
CEO of Resilience
Regulate body and nervous system
Quell fear response of amygdala
Manage emotions
Attunement – felt sense of feelings
Empathy – making sense of experience
Insight and self-knowing
RESPONSE FLEXIBILITY
Planning, decision making
MoralitySlide72Slide73Slide74
Figure 2. Selected genetic variations and epigenetic modifications associated with altered hypothalamic-pituitary-adrenal (HPA) axis regulation conferring stress vulnerability. Individual differences in HPA axis functionality are determined by genetic variants (left box) and epigenetic modifications (right box) of genes coding for glucocorticoid (GC) receptor (GR; NR3C1) and mineralocorticoid receptors (MR; NR3C2), as well as other components of the HPA axis cascade (CRH, CRHR1, AVP, POMC). To strengthen the relevance of these changes to HPA axis regulation, we focused here only on studies with clear measures of HPA readouts from healthy humans and excluded deliberately patient studies (for a review on such data see e.g. [
8
]). Single nucleotide polymorphisms (SNPs) related to changes in HPA axis reactivity are primarily localized in GR, MR and FKBP5 genes. Reduced or impaired GR and MR function, for example, reduced glucocorticoid sensitivity (GC-S ↓) or glucocorticoid hypersensitivity (GC-S ↑) and associated altered feedback inhibition via GCs (red lines) has been suggested to underlie HPA axis dysfunctions (hyperactivity or
hypoactivity
) in stress susceptible individuals. Epigenetic mechanisms such as DNA methylation and histone modifications have been shown to modulate gene expression at different levels of the HPA axis and in different brain areas (right box) regulating HPA axis and implicated in shaping stress-vulnerable phenotypes (for review see [
11
;
12
]). AMY, amygdala; AVP, arginine vasopressin; BNST, bed nucleus of
stria
terminalis; CRH, corticotropin releasing hormone; CRHR1, CRH1 receptor; GC-S, glucocorticoid sensitivity; GR, glucocorticoid receptor; HIP, hippocampus;
mPFC
, medial prefrontal cortex; MR, mineralocorticoid receptor;
periPVN
, perinuclear PVN area; POMC, Proopiomelanocortin; PVN, paraventricular nucleus.Slide75
Effects of glucocorticoids on the hypothalamic-pituitary-adrenal (HPA) axis.
Robert Newton Thorax 2000;55:603-613
Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.Slide76Slide77
Figure 1 The major components of the stress response mediated by the hypothalamic–pituitary–adrenal (HPA) axis. Both alcohol and stress can induce nerve cells in one brain region (i.e., the hypothalamus) to produce and release corticotropin-releasing factor (CRF). Within the hypothalamus, CRF stimulates the release of a hormone that produces morphine-like effects (i.e.,
β-
endorphin). CRF also is transported to a key endocrine gland, the anterior pituitary gland. There, CRF stimulates production of a protein proopiomelanocortin (POMC). POMC serves as the basis for a number of stress-related hormones, including adrenocorticotropic hormone (ACTH),
β-
lipotropin
(
β-
LPH), and
β-
endorphin. ACTH stimulates cells of the adrenal glands to produce and release the stress hormone cortisol. When cortisol levels reach a certain level, CRF and ACTH release diminishes. Other neurons releasing serotonin (5-HT), norepinephrine (NE),
γ-
aminobutyric acid (GABA), or endogenous opioids also regulate CRH release.
Note: plus = excites; minus = inhibits.Slide78Slide79Slide80
Trauma definition
Between 50 and 60% of people experience a severe traumatic event in their lifetime
Has a cause
Effects continue after the cause has ceased
Has human victims
Intangible
Feeling
'possibility of emotional trauma is built into the basic constitution of human existence' (p. xi) and the way in which it is permitted to emerge is largely governed by the relational context in which we find ourselves.Slide81
Resilience IMPORTANT CONCEPT
It is important to note that although research has outlined numerous ways in which developmental environment can negatively impact a person, resilience is in fact a common trait, following even the most severe adversities. Between 50 and 60% of the general population experience a severe trauma during their lifetime, yet the prevalence of PTSD is estimated at 7.8% (
Russo et al., 2012
). Other studies have found that neural circuits involved in resilience can be modified for many years after adversity.
For instance, the majority of adolescents whose development was stunted in childhood due to trauma were able to developmentally “catch-up” when relocated to a supportive, loving environment (
Masten
, 2001
;
Rutter, 2012a
).
The fact that not all animals or humans exposed to uncontrollable traumatic experiences develop stress-related disorders clearly implies that environmental factors interact with genetic endowment and together, affect resilience. In fact, resilient genes may be sufficient to help a person overcome the most traumatic developmental events in some cases (
Feder et al., 2011
).Slide82Slide83
epigenetics
Ways your DNA can be read or covered up:
Methylation
Histones
Chromatin folding and attachment to nuclear “matrix”
Packaging of DNA around nucleosomes
Covalent modification of histone tails (
eg
. Acetylation, methylation, phosphorylationSlide84Slide85
epigenetics
Epigenetics refers to functional modifications to the genome without change in the DNA sequence. Such modifications serve to regulate gene expression and phenotype through mechanisms such as DNA methylation and demethylation, as well as histone modifications including methylation, acetylation, and phosphorylation. Epigenetic differences can be a consequence of exposure to stress-related factors during critical periods of development, and hence contribute to susceptibility to psychiatric disorders (
Tsankova
et al., 2007
;
Dudley et al., 2011
).
Ways your DNA can be read or covered up:
Methylation
Histones
Chromatin folding and attachment to nuclear “matrix”
Packaging of DNA around nucleosomes
Covalent modification of histone tails (
eg
. Acetylation, methylation, phosphorylationSlide86
Histone methyltransferases (e.g., GLP, SUV39H1, G9a) are down-regulated in the nucleus
accumbens
of susceptible mice exposed to chronic social defeat stress, while these molecules were up-regulated in resilient mice exhibiting low depression-like responses, suggesting that histone methylation may be adaptive in the face of stress and protect against development of depression (
Covington et al., 2011
)
Maternal care was found to influence stress response through epigenetic alterations, with offspring of high maternal care showing increased hippocampal GR expression and enhanced glucocorticoid negative feedback sensitivity, and hence more modest HPA response to stress, through hypomethylation at the NGFI-A nerve growth factor-inducible protein A (NGFI-A) binding site of a GR promoter (
Weaver et al., 2004
).Slide87
environmental
Developmental environment is another crucial contributor to resilience (
Rende
, 2012
). Severe adverse events in childhood can negatively affect the development of stress response systems, in some cases causing long-lasting damage. Numerous rodent and primate studies suggest that animals abused by their mothers in the first few weeks of life show both delayed independence and decreased stress management skills in adulthood (
Feder et al., 2011
). These changes are reflected in abnormally high anxiety levels, increased HPA axis activity, and increased basal CRH levels in the cerebrospinal fluid (CSF) (
Strome et al., 2002
;
Claes
, 2004
;
McCormack et al., 2006
). It is important to note that non-human primates, who have suffered childhood abuse, resulting in damaged stress response systems, may be more likely to abuse their own children (
Maestripieri
et al., 2007
). In this way, the cycle of abuse is continued through generations.
Prenatal stress and childhood trauma have been linked to a hyperactive HPA axis with attendant risk of negative effects of chronic hypercortisolemia later in life (
Frodl
and
O'Keane
, 2012
)Slide88
Environment
cont
Childhood abuse can lead to a reduction of hippocampal volume, which is frequently seen in patients with mood disorders (
Janssen et al., 2007
;
Davidson and McEwen, 2012
). As the hippocampus is one of the most plastic regions of the brain, there is hope that pharmacological treatments, such as antidepressants, may be able to reverse this decrease in volume by increasing neural progenitor cells (
Boldrini
et al., 2012
). PET studies have also revealed decreased activation in the hippocampus during memory tests in patients with a history of childhood abuse (
Heim et al., 2010
). Other brain areas seem to be affected by childhood abuse as well. For instance, a recent study suggests that childhood maltreatment has a pronounced effect on two separate neuroimaging markers—reduced hippocampal volume and amygdala responsiveness to negative facial expressions (
Dannlowski
et al., 2012
). Chronic, unmanageable social and psychological stress, and maltreatment, especially early in life, are also linked to shorter telomeres, which have been associated with increased risk of developing somatic diseases such as cancer, diabetes and heart diseases, and psychiatric disorders, particularly depression (
Blackburn and
Epel
, 2012
;
Price et al., 2013
).Slide89
Environment(?)
cont
Certain factors play major roles in determining whether a childhood traumatic event will lead to vulnerability or instead, to resilience. One of these factors is the degree of control that the person has over the stressor (
Feder et al., 2011
). Episodes of early uncontrollable stress can lead to “learned helplessness,” where a person is conditioned to believe that they are unable to change the circumstances of their situation (
Overmier
and Seligman, 1967
). Learned helplessness is also used as a model for depression in animals. When administered inescapable and erratic shocks, animals tend to develop heightened anxiety states and fear responses (
Overmier
and Seligman, 1967
). Furthermore, their active coping is reduced when faced with later stressors. Learned helplessness in animals is also believed to lead to dysregulation of serotonergic neurons in the dorsal raphe nuclei (
Greenwood et al., 2003
), as well as a reduction of cell proliferation in the hippocampus (
Ho and Wang, 2010
). These dysregulations are likely to have severe negative repercussions on both cognition and mood.Slide90
Stress
innoculation
On the other hand, when animals are administered shocks that are avoidable by behavioral modification, learned helplessness does not seem to develop (
Seligman and Maier, 1967
). In this same way, humans that have been able to successfully master a mild or moderate stressor (for example, the end of a friendship or illness of a parent) appear to be resilient to a variety of other later stressors (
Feder et al., 2009
;
Russo et al., 2012
). This phenomenon is called “stress inoculation,” and occurs when the person develops an adaptive stress response and a higher-than-average resilience to negative effects of subsequent, uncontrollable stressors (
Southwick and
Charney
, 2012
). Stress inoculation is a form of immunity against later stressors, much in the same way that vaccines induce immunity against disease (
Rutter, 1993
). Research in rodents supports the stress inoculation hypothesis and has suggested that this protection against some of the later negative effects may be due to neuroplasticity in the PFC induced by stress inoculation (
Southwick and
Charney
, 2012
). In one study, young monkeys were presented with a controllable stressor (periodic short maternal separations) over a course of 10 weeks (
Parker et al., 2004
). These monkeys experienced acute stress during the separation periods, illustrated by agitation as well as temporary increased levels of cortisol. Yet, at 9 months of age, they experienced less anxiety and lower basal stress hormone levels than monkeys who did not undergo the separations. Additionally, at later time points, the group of stress-inoculated monkeys showed higher cognitive control, higher curiosity in a stress-free situation and larger ventromedial PFC volume (
Parker et al., 2005
;
Lyons et al., 2009
).Slide91
Surprise?
Besides children from an abusive and life-threatening environment, a newly identified group at risk is youth from affluent families, who may face higher risk of adjustment problems (e.g., substance use, depression, and anxiety) (
Luthar
and
Barkin
, 2012
). Parents' lax repercussions on discovering substance use was shown to be a major vulnerability factor. Moreover, the levels of teens' symptoms (rule breaking, anxious-depressed, and somatic symptoms) were found to correlate more strongly with the teens' relationships with mothers than with fathers, which may in part reflect greater amount of time spent with mothers, who are generally the primary caregivers of their children. Therefore, positive changes in parenting for affluent youth are of critical importance, including adopting a strict zero-tolerance policy regarding students' law breaking, remaining vigilant about their children's activities outside school, and engaging in talks and workshops for families in distress and holding support groups particularly for mothers (
Luthar
and
Barkin
, 2012
).Slide92Slide93
What influences change gene expression?
PRENATAL:
Starvation during pregnancy
Stress during pregnancy
LIFE-LONG
Think of the entire environment: food, shelter, safety, relationshipSlide94
There are several studies on associations between maternal pregnancy anxiety and outcomes in their children. However, these efforts cannot determine how much of the effects are due to genetic transmission of anxiety, effects of stress hormones on the uterine environment, and maternal modelling of anxiety after birth.
Project Ice Storm
is the only project in the world that (1) studies the effects of an independent stressor; (2) and is, thus, able to separate effects due to objective exposure to the event from the mother's subjective reaction to it, while controlling for trait levels of anxiety and depression; (3) is studying effects prospectively since shortly after a stressful event and while most of the sample was still pregnant; (4) and has a prospective sample of greater than 100 families. To date, we have obtained significant effects of prenatal maternal stress in every area of development that we have examined. Extrapolating our findings to more severe events, such as war and other forms of natural and man-made disaster, the strong effects we find may possibly be multiplied in other contexts.Slide95
Messages and messengers of the body
Endocrine /hormones
Apokrine
Receptors
NeurotransmittersSlide96
Neurotransmitters and moodSlide97
Dorsal
vagus
nerve –the “dumb”
vagus
Older “dumb” dorsal
vagus
Fear-danger-life threat
Dorsal dive – numb out, collapse
Powerlessness, lethargy, isolation, shameSlide98
Polyvagal theory – Dr. Stephen
Porges
Neuroception
of safety-danger-life threat
Newer “smart” ventral
vagus
Safety of social engagement
Eye contact, facial expressions, tone and prosody of voice, “
motherese
”
Down-regulate spike of sympatheticSlide99Slide100Slide101
Polyvagal theory – Dr. Stephen
Porges
Neuroception
of safety-danger-life threat
Newer “smart” ventral
vagus
Safety of social engagement
Eye contact, facial expressions, tone and prosody of voice, “
motherese
”
Down-regulate spike of sympathetic
Older “dumb” dorsal
vagus
Fear-danger-life threat
Dorsal dive – numb out, collapse
Powerlessness, lethargy, isolation, shameSlide102Slide103