early life adversity, hormones and mood Flashcards
lecture outline
early studies in ELA
HPA programming
prenatal adversity
insulin as key player in relationship between ELA and adult disease
affective disorders and different hormonal axes
- thyroid
- glucocorticoids
- ovarian hormones
- insulin
modulation of these hormonal axes can result in affective disorders
early papers: “the long-term prognosis for prematurely born children”, “a study on birthweight and intelligence”
approaching notion that early life is super important for health across lifetime
Kermak et al quote from The Lancet
“we are thus led to a picture which is unexpected. each generation after 5 years of age seems to carry along the same relative mortality throughout adulthood and even extreme old ages. figures behave as if expectation of life was determined by conditions which existed during a child’s earlier years”
Harlow Zimmerman monkey studies
monkey studies showed:
baby monkeys prefer the cloth “mother”
over the cage with the bottle
animal study looking at early development
Barker and Burnside
huge jump in the field - looking at HUMANS
used Burnside’s detailed notes on birth conditions of now old men
noticed association between BIRTH WEIGHT and risk for DISEASE in adulthood
arrived at METABOLIC ODDS RATIO
small babies = higher risk of mortality 80 years later
one problem with Barker/Burnside analysis
only examines birthweight
not other factors like if the baby was born at term or premature
there are also other factors that affect birthweight (ie. size of mother) that need to be considered
Barker/Burnside odds ratio
as birthweight increases, lower odds ratio for metabolic syndrome
among 407 men born in Hertfordshire
5.5 and lower = at a MUCH higher risk
in the 1940’s-1990’s, developed a better understanding of…
- stress response
- critical periods of development
HPA axis quick overview
when faced with stressors, there’s a sequence of responses
- sensory mechanisms of brain interpret stressor
- CRH and ACTH are released
- glucocorticoids travel through bloodstream
- but glucocorticoids travel back to brain and inhibit the axis
negative feedback!
classical studies: understanding of stress response
progressed during 1940’s-1990’s
negative feedback and glucocorticoid response unveiled
classical studies: critical periods of development
progressed during 1940’s-1990’s
- birth
- sensory development
- motor/language development
- higher cognition
develop different systems throughout infancy, childhood and adolescence
discovered that if animal is in early sensitive period (sensory stage) and experiences a big disruption, systems will be altered forever
like a scar in that system
example of effect of disrupting event/insufficient stimuli during critical period
myopia
if part of visual field doesn’t receive info early on, that part of field will be blind forever
HPA axis is subject to this all well
what happens if a stressor occurs during the development/programming of HPA axis?
will make the axis work differently forever
Liu et al important study SETUP
revolutionized the field
observed rats in cages and how their mothers cared for them - no intervention
let pups grow to adulthood
examined their HPA response to stress (ACTH secretion)
Liu et al important study FINDINGS part 1
- found a NORMAL DISTRIBUTION of maternal behaviour
a) HIGH care mothers and LOW care mothers
- both high and low maternal care receivers respond, but…
a) low care receivers respond MORE and it takes LONGER for their stress response to be shut down
negative feedback of low childhood care receivers is LESS EFFICIENT
Liu et al important study FINDINGS part 2
- looked at HIPPOCAMPUS
a) more glucocorticoid receptors in HIGH CARE rats - this facilitates NEGATIVE FEEDBACK
b) gene expression was different: transcription factor for glucocorticoid receptor gene
in high care rats, there were more ______ ______, which facilitates _____ _____
glucocorticoid receptors
negative feedback
gene expression different in LOW CARE rats
hippocampus of LOW CARE rats had different gene expression
transcription factor for glucocorticoid receptor gene
DNA methylation (epigenetic change) makes it harder for transcription factor to bind to gene
higher methylation in a place that made transcription harder for glucocorticoid receptors in rats who had received LOW CARE
programming of HPA axis in humans chart SETUP
birth weight is associated with cortisol stress response
- gave 10-12 year olds a social test that induced stress
- collected biological tissue and measured cortisol
programming of HPA axis in humans chart RESULTS
- those born small had higher cortisol response to acute stress
- with every single daily stressful event, there’s an increase in glucocorticoid response
a) chronic exposure to glucocorticoids has all sorts of effects
