Lecture 6: resilience vs. vulnerability

Question 1

Factors that influence the outcomes of childhood maltreatment

Answer 1

1. Type (neglect/abuse/physical)
2. Timing (developmental period)
3. Severity & chronicity
4. Perpetrator (random/close)

Question 2

Disthesis stress model / dual risk model

Answer 2

People have different diathesis (susceptibility) to adverse life events (like childhood maltreatment). Those with higher diathesis (greater susceptibility) are more likely to develop negative effects after maltreatment, while lower diathesis can cause less negative effect.

Question 3

Differential susceptibility model

Answer 3

Some people are more ‘sturdy’; the environment doesn’t influence them a lot. Other people are more sensitive to environmental factors. They will thrive in a positive environment and fail in a negative environment.

Question 4

Social support

Answer 4

Is one of the most robust buffers of early life stress. BUT: subjective experience of social support can be affected by stress.

Question 5

Psychosocial resilience factors

Answer 5

• Social support
• Relationships / attachment
• Focus on the (broader) system
• Self-esteem & coping (COMET)

Question 6

Resilience building

Answer 6

A way to see resilience as a form of positive adaptation to life circumstances. Building resilience can be done by:
- Focussing on changeable/ amenable factors.
- Using coping strategies.
- Involving (foster) parent, professional care and close community.
- Social connectedness.
- Sensitivity from social network (parents/ teachers).
- Showing warmth
- Providing predictability and trust
- Increasing stress tolerance by moderate, repetitive (predictable) stress.
- Brain functionality

Question 7

Cognitive control of the brain

Answer 7

Greater use of the fronto-parietal networks during reappraisal causes better emotion regulation, which can cause resilience to negative outcomes. This can be trained in cognitive behaviour therapy.

Question 8

Genetic vulnerability / resilience

Answer 8

Different genes impact the regulation of hormones and neurotransmitters that play a role in: growth, development, stress and psychopathology. This can cause a genetic disposition for certain physical and mental diseases. These neurotransmitters are:
- Serotonin (5-HTT, SLC6A4)
- Cortisol (glucocorticoids)
- Dopamine (DRD4)
- Oxytocin (OXTR)
- Brain derived neurotrophic factor: BDNF

Question 9

Nucleotides

Answer 9

You’re whole DNA is build up from 4 base pairs of nucleotides (ATGC):
- Adenine
- Thymine
- Guanine
The order of the nucleotides can determine the order of a protein. Proteins have many different functions (enzymes, immune system, stress hormones, neurotransmitters etc.). In different cells, there are different genes (proteins) active –> proteins determine the function of the cell.

Question 10

Alleles

Answer 10

Alleles are variants of a gene. Certain genes are the same for everybody and other genes have ‘alleles’, which means that there are differences in genes between people. This is called polymorphism: the variations in the genes that are present in the population (=normal viration).

Example: Eye colour. People have the same genes for eyes (because we all have eyes), but some have a different colour (=different allele).

Question 11

Single Nucleotide Polymorphism (SPS)

Answer 11

When there is only one little change in the nucleotides in the whole strong of DNA (out of 6 million). In most cases, this doesn’t really matter, but the place of the change in the nucleotides can influence the function of the gene (like in 5-HTT).

Question 12

Serotonin Transporter (5-HTT) polymorphism

Answer 12

The 5-HTT gene encodes for the serotonin transportation. You can have a short allele and a long allele of this gene, which determines how active the serotonin transporter gene is transcribed:
- Short allele: causes lower serotonin-reuptake –> more susceptibility to stress –> higher chance of depression after stressful life events.
- Longe allele: less susceptibility to stress.

Question 13

Short 5-HTT allele is related to

Answer 13

• Stress sensitivity (hormones, brain activity)
• Depression and anxiety measures of behaviour
• Depression phenotypes
• Negative affectivity

Question 14

Conclusion about polymorphism of the 5-HTT gene

Answer 14

Only in a stressful environment is polymorphism (difference in alleles) expressed. This is called a gene-environment interaction.

Question 15

Why did these gene variations survive evolution?

Answer 15

Because certain genotypes do well in certain environments (like stress resilience) and very bad in other environments.

Example: a child that is less susceptible to stress might still try to stand op to their caregivers when abused, this can make the abuse even more. Expression of a short allele of the 5-HTT gene can then cause more stress sensitivity –> adaptive in a stressful environment (but not in later life).

Question 16

Can genetic traits be changed?

Answer 16

CRISPR gene editing is a genetic engineering technique by which the genomes of living organisms may be modified (or the activity of those genes). But this is still far away from changing brain function!

Question 17

Epigenetics

Answer 17

The effect of the environment on the expression of genes, without changing the order of the DNA nucleotides, but with changes in the regulation of genes. These changes can be temporary of permanent.

Question 18

Closed and open chromatin

Answer 18

• Closed chromatin: when DNA is very closely wound up –> nothing can enter –> no activation.
• Open chromatin: when DNA is openly wounded dup –> potential for activation of genes.

Question 19

Methylation

Answer 19

This impacts how open or closed a gene string is. When there is a lot of methyl groups on the promoter region of the gene, then the gene is NOT active. If however, because of stimuli (like a stressor), the methyl groups are taken away, then the promoted region becomes open (open chromatin) and the gene can become active.

! Methyl groups can be seen as the guards that keep the gate shut –> no activation or open them –> activation.

Example: during a stressful event we want to produce more cortisol. This sends a signal to take the methyl groups away, which makes the chromatin open up and activates the cortisol promoter region. This is how the amount of stress can affect the activity of the gene (=GxE interaction).

Question 20

Therapies

Answer 20

Can also influence how the genome is regulated and which genes are activated due to GxE interactions.

Example: a fat mice received foor rich in vitamins, which caused the mother to give birth to thin mice that were no longer vulnerable to the same gene expression as the fat mother.

Question 21

The effect of trauma

Answer 21

May impact the regulation of the DNA via epigenetics (GxE), by impacting the activity of many different cells/tissues/organs/systems (like the HPA-axis, insulin, immune system).

Question 22

Glucocorticoid Receptor (GR) gene

Answer 22

When this gene is regulated differently, this causes different levels of cortisol after stress.

Question 23

Study to methylation and expression of the GR-gene (in suicide victims with a history of childhood maltreatment)

Answer 23

In these people, they found a decreased glucocorticoid expression, which is related to higher levels of methylation in the promoter region of that gene, which causes more suppression of that gene –> inadequate cortisol production –> potential depression-like behaviour (?)

Question 24

Childhood trauma also influence the methylation of genes in:

Answer 24

• The hippocampus
• The blood
• The 5-HTT gene (serotonin)
• The OXTR gene (oxytocin)
• The BDNF gene
• The immune system

Question 25

Prenatal stress

Answer 25

Causes methylation of the GR-gene in children (less expression of glucocorticoids). This can cause the child to have epigenetic tags related to this. But: food intake during pregnancy can influence how epigenetic outcomes/ activation of these genes (genes being switched on/off.