Brain Story Certification: Module 3

Module 3 focuses on gene signatures and how gene-environment interactions shape the architecture of the brain (epigenetics).

Excerpt from “Eight (failed) Assumptions: What we thought we knew about early childhood development.” Tom Boyce, MD

• One assumption is that our destiny is in our genes.  Science suggests that:
  • Most traits & diseases are derived from:
    • not just our genes/nature
    • not just from nurture/environment
    • not even just a combination of nature + nurture
    • it is the gene-environment interactions.
• Within the cell, the packaging DNA and messaging it receives impacts the ability to express, or turn on the expression of, the gene.
• Epigenetics: the study of environmental factors that influence whether or not a gene within DNA will be expressed without altering the DNA sequence.
• Epigenetics thus explores if the environments allow for the gene to carry out its function or not.

Excerpt from “Biological Embedding of Stress in Early Development.” Michael Meaney, PhD

• Parental care influences the activity of genes that regulate the stress response and brain development – the parental effect influences the DNA’s ability to express certain genes.  Functional changes to a genome indicate the ability of a gene’s ability to be expressed.
•  Multiple phenotypes (expressions of characteristics) come from a common genotype (set of genes in the DNA).
• Methylation influences the ease in which a gene can be expressed.
• The pathways of parental care to phenotype are as follows:
  1. Parental care
  2. Epigenetic mark
  3. Gene expression
  4. Phenotype
• Chronic stress, induced on mother rats, changed their parenting rituals on the rat pups.  This, in turn, impacted the environment the mother created with the pup.  This had epigenetic implications on the pup.  In cross-fostering studies, the effects can be reversed – suggesting the importance of parenting on developmental outcomes.  This is impacted by the endocrine system (glucocorticoids, CRF, & ACTH).  The genes that produce the proteins that influence the number of receptors in the brain are impacted (less expressive – as methylation closes it from producing the protein) and thus a mechanism where the gene-environment influences behaviour.
• This may impact resilience through the HPA axis?
• Maternal care has the potential to influence the methylation of genes that impact the HPA axis – changing the individual’s ability to work with neurotransmitters that then influences brain activity such as stress responses.

Excerpt from “Biological Embedding of Stress in Early Development.” Michael Meaney, PhD.

• Forensic phenotyping: interviewing the family of a deceased individual to develop a profile of the psychopathology that may have been present in an individual through a validated interviewing process. The interviewer can also explore the developmental history of an individual.
• Tissues can be examined – looking at the glucocorticoid receptor gene.  Decreased receptor activity in the DNA is correlated with those who die as a result of suicide.
• The link to abuse – childhood maltreatment (physical or sexual) – was a factor, along with “profound emotional neglect.”  Methylation of the gene was high in those who experienced abuse and died by suicide.
• Meaney brings up environmental enrichment experiments for rats.  Specifically, can it offset the impacts of adversity on the epigenome?  The environment was about two times more impactful on creating changes in the epigenome than the maternal interaction in the rats.

Excerpt from “Risk, Resilience, & Gene-Environment Interplay in Primates.” Stephen Suomi, PhD

• An examination of personality/temperament in Rhesus Monkeys and their underlying biological mechanisms.
• Look at how the environment interacts with biology to influence personality/temperament.
• 20% have high fear/anxiety to novel experiences/circumstances.  This includes high activation of the sympathetic nervous system & HPA axis.
• 5-10% unusually impulsive – do things that disrupt the mores in the group.  Elicit a lot of aggression from others, and display more aggression than others.  They have uniquely lowered serotonin metabolism – particularly 5-HIAA.  Higher degrees of aggression (may be linked with conduct disorders)
•  Early social environments are very important in the development process for the monkeys (and people).  This is centred around attachment figures, and their influence on neuroendocrine function, neurotransmitter metabolism, brain structure, and gene expression.
• Rhesus Monkeys develop a similar attachment to caregivers as humans do.  Mother’s are picky about who can connect with children.
• The secure base in these monkeys is very similar to attachment theory in humans. It takes place between the 2-6 month period of life in the monkeys.
• Returning to the secure base is equally important in the infant Rhesus monkey’s exploration of their environment.
• Experiments on separation from the birth mother (and fostering) have taken place at this facility.  Peer groups of monkeys all separated has also taken place for the first 6 months of life.
• Peer groups develop attachments with one another.  These are dysfunctional attachments as they cling to one-another longer than if they had a primary attachment figure, leading to less exploration.
• Subsequent levels of play for peer groups are less than those with a secure attachment figure.
• As the peer-attached monkeys grow up, they become more fearful of stimuli than those who experienced a secure attachment figure in infancy.  They display characteristics similar to the 20% of the population that is more naturally fearful.  They show greater releases of cortisol under challenge conditions in comparison to securely attached counterparts.
• These monkeys also become more aggressive – similar to 10% of the natural population who have a lowered serotonin metabolism.
• In conditions where monkies are given access to alcohol, the peer-attached monkeys consume more sweet-water-alcohol mix as opposed to sweet-water, or plain water.  Thus, several pathways of neural function are impacted by disruptions in the attachment.
• 1/5th of the genome was more methylated in the peer-attached monkeys, impacting gene expression.

Excerpt from “Risk, Resilience, & Gene-Environment Interplay in Primates,” Stephen Suomi, PhD.

• 5-HTTLPR Alleles are genes used to produce proteins involved in the reuptake of serotonin pre-synaptically.
• The shorter 5-HTTLPR alleles are associated with poorer reuptake function.
•  Mother-reared monkeys are not impacted by the RH5-HTTLPR and CSF 5-HIAA genes, where peer-reared monkeys are more impacted by the genes.  So the vulnerability in the genes becomes exposed when the child development environment is disrupted.
• In alcohol consumption, the short allele is associated with excessive drinking in the monkeys.  While having a short allele with a secure attachment figure reduces the likelihood of excessive drinking.
• Thus, vulnerabilities and protective factors are relative to the environment and attachment the infant is exposed to in their brain and epigenetic development.
• These findings have been replicated in multiple other neural metabolism protein gene alleles, where the short and long versions impacts on behaviours are neither inherently good or bad on outcomes, but dependent on the environment/attachment available to the infant monkey (less efficient gene paired with peer-rearing correlated with adverse outcomes; less-efficient gene paired with secure attachment figure such as mother-rearing has a good or better than average outcome). This is “maternal buffering”
• Mothering styles are usually inter-generationally transmitted by non-biological means – connecting childhood experiences to intergenerational development outcomes.  This is why the “nature” part of “nature” vs “nurture” may not be as evident in circumstances where there is an opportunity for good attachment and low maternal stress.   Things that compromise the environment can thus compromise the risk factors for the young.

Excerpt from “All About Brain Architecture.” Judy Cameron, PhD.

• Introducing stressors in specific critical periods of development.
• Baby and mother placed into a group environment with a diverse set of genders and ages to simulate a family context – mother was most dominant to prevent fighting situations.
• As baby ages, it reduces contact with mother – exploring the environment.
• Separation situations that would simulate the death of the mother take place.  The other monkies are left with the baby monkey – similar to a family situation.  Situations included separation at 1 week, one month, and 3 months.  Each of these outcomes was different.
  • Behaviour at 1-week separation:  No close social contact, although some social interaction with the surrogate “family”.
    • When it grows up, there are deficits in social interaction.
    • This was an adverse experience that reduces grooming behaviours in adulthood with other monkeys.
    • Otherwise, the monkey appears quite normal.
    • Later in life, the amygdala gene expression changed occurred in over 200 genes.
    • Low-level genes were generally now expressed high, and high-level genes were expressed generally low under the experimental condition of 1 week.
  • Behaviour at 1-month separation.  Not as much of a change in social interaction.
    • Some changes in gene expression, but is different from the control and one week groups.
• Life-long changes to the genes and expressions throughout life.

Excerpt from “Biological Embedding of Stress in Early Development.” Michael Meaney, PhD

• How will we integrate genetics into interventions for individuals?
• Look at genotype impacts as part of the outcome – but this does have ethical implications.
• We need to have a clear definition of the components of epigenetics along with outcome indicators to examine if the interventions are evidence-based.

References

Alberta Family Wellness. (n.d.). Brain story certification.  Retrieved from https://training.albertafamilywellness.org/