Introduction lecture: Etiology of mental traits and disorders

Question 1

Understanding etiology of disease can be a complex puzzle. What two factors belong in this complex puzzle?

Answer 1

Genes and environmental factors, there’s interaction between these two factors.

Question 2

How can environmental factors exert their influence?

Answer 2

By altering gene expression via stress systems or epigenetics

Question 3

What kind of study is used to study heritability in regard to mental traits and diseases?

Answer 3

Twin studies and adoption studies

Question 4

What is the definition of the variable heritability?

Answer 4

The proportion of variance in symptoms that is explained by the variance in genetic factors (on population level)

Question 5

Explain what it means that ADHD has a heritability of 75%.

Answer 5

There’s a lot of variability in symptoms of ADHD, some ADHD-patients have more problems in e.g. attention than other patients do and even healthy people (so no ADHD) is considered as variability in ADHD. A heritability of 75% in ADHD means that 75% of this variability is due to the variability in genes. The 25% that is left, is the 25% variability in ADHD that is due to exposure to variable environmental factors.

Question 6

What is so hard about finding risk genes?

Answer 6

That it’s not only a matter of dominant and recessive genes. A trait arises due to many different interactions between genes.

Question 7

What is the classic theory of how genes can cause disease/mental illness (classic theory of inherited disease)? Why is this theory not correct?

Answer 7

A single abnormal gene will lead to an abnormal gene product, which will lead to neuronal dysfunction, which leads to metal illness.

This theory is not correct, since one abnormal gene is not sufficient to cause mental illness.

Question 8

New explanations, hypotheses and models are generated for the pathway from ‘genotype to phenotype’. During this course three models/hypotheses are discussed. What model is discussed in this lecture?

Answer 8

Complex genetics / Diathesis-Risk Model

(diathesis=risk)

Question 9

How does disease arise based on the Diathesis-Risk Model?

Answer 9

Disease is caused by multiple small contributions from several genes (predisposition), all interacting with environmental stressors.

Question 10

To explain the phenotype based on the genotype (from genotype to phenotype) is very complex. Therefore, a new approach has been researched. What approach is this?

Answer 10

The endophenotype approach, there are important intermediaries between genotype and phenotype.

Question 11

Explain what an endophenotype is.

Answer 11

An endophenotype is measurable/quantifiable.

Let’s say a certain genotype leads to a subtle abnormality in a molecule. This abnormality of the molecule will result in abnormal information processing of e.g. the cortex. This abnormal information processing of the cortex can then lead to a symptom or behavior that is associated with this abnormal information processing. An endophenotype here is the abnormal information processing that is due to a certain genotype and causes a certain symptom or behavior, which is associated with the disease.

Question 12

What two types of endophenotypes exist?

Answer 12

• Biological endophenotypes, a measurable biological process that occurs due to an abnormal genotype.
• Symptom/system endphenotypes, a single symptom that is associated with a mental illness.

Question 13

Think of why endophenotypes are important in linking a certain process to genes.

Answer 13

Consider the pathway from gene → molecule → circuit → information processing → single symptom → full syndrome of disorder.

Based on this pathway, genes are only loosely linked to psychiatric disorders and therefore risk genes are hard to identify. Therefore endophenotypes can be used to link certain processes to genes. If an endophenotype is closer to a gene on the pathway, it’s more readily linked to a gene.

Question 14

If the etiology of psychiatric disorders is moving beyond receptors, enzymes and other molecules as causes for mental ilnesses, what else is thought of to be the cause of mental ilnesses? And what could this be the consequence of?

Answer 14

Malfunctioning specific brain circuits are being linked to psychiatric symptoms as a consequence of genes in combination with environmental risk factors.

(Therefore brain imaging should focus more on brain circuits.)

Question 15

What is the social-ecological framework?

Answer 15

No single factor can explain disease. This framework explains the dynamic interplay of multiple risk and protective factors. These factors occur along a social ecology continuum: individual → relationship → environment.

Question 16

What is a very important environmental risk factor for disease?

Answer 16

Pre- and perinatal risk factors, such as:

• Maternal stress during pregnancy
• Maternal nutritional deficiency
• Maternal use of tobacco/alcohol/drugs/medication
• Birth complications
• Perinatal nutritional deficiency
• Maternal separation

Question 17

Name other environmental risk factors.

Answer 17

• Abuse (sexual, physical or emotional)
• Neglect
• Poor parental care
• Infections
• Toxins
• Brain trauma
• Drug use
• Stressful life events
• Low SES
• Poverty
• Community violence
  (Mental) health care (policy)
• Minority group position
• Cultural factors
• Religious factors

Question 18

There are two stress systems: the fast-acting pathway and slow-acting pathway. Explain the fast-acting pathway when the brain detects a threat.

Answer 18

1. The hypothalamus sends a neural message through the spinal cord.
2. The sympathetic part of the autonomic nervous system (ANS) is activated to stimulate the medulla of the adrenal gland.
3. The medulla releases epinephrine into the circulatory system
4. Epinephrine activates the body’s cells.

Question 19

There are two stress systems: the fast-acting pathway and slow-acting pathway. Explain the slow-acting pathway when the brain detects a threat.

Answer 19

1. The hypothalamus releases CRF into the pituitary gland.
2. ACTH is released onto the cortex of the adrenal gland.
3. This releases cortisol into the circulatory system
4. Cortisol activates the body’s cells.

Question 20

What is another name for the slow-acting pathway of stress?

Answer 20

Hypothalamus-Pituitary-Adrenal axis (HPA-axis)

Question 21

How is cortisol able to induce gene expression in the body’s cells?

Answer 21

Cortisol will bind to its glucocorticoid receptor (GR) and as a response the intracellular part of GR will translocate to the nucleus and will act like a transcription factor.

Question 22

What does cortisol induce?

Answer 22

• It activates the cardiac system by binding to cardiac cells, which results in increased contraction and with this increased blood pressure.
• It inhibits the immune system. The immune system costs a lot of metabolic energy, this energy needs to be preserved in a stressful environment.

Question 23

How is cortisol production inhibited?

Answer 23

Via negative feedback: there are glucocorticoid receptors (GR) located in the hypothalamus, hypophysis and hippocampus. When the concentration of cortisol is high, cortisol will bind to these receptors and the signal cascade that leads to cortisol production is halted (by e.g. shuw down of CRF release).

Question 24

Fill in:

A healthy stress system is one with plenty or few glucocorticoid receptors (GR). This is important for …

Answer 24

A healthy stress system is one with plenty glucocorticoid receptors (GR). This is important for negative feedback.

Question 25

What are effects of sustained high levels of cortisol on the body?

Answer 25

• Cardiovascular disease, hypertension
• Immunosuppression
• Structural effects on hippocampus and amygdala
• Increased chance psychopathology

Question 26

What is the consequence of early life stress?

Answer 26

The HPA-axis is overactive life long, with less GR and thus less negative feedback to shut down cortisol production. This results in hyperstress.

Question 27

What are epigenetics?

Answer 27

Epigenetics are changes on the DNA instead of in the DNA. Epigenetics can be part of normal development or due to environmental factors and can chemically coat DNA. This affects how easy genes on DNA are accessed and thus how genes are expressed. It does not affect the genetic model/DNA itself.

Question 28

Just study this picture.

Answer 28

Ok

Question 29

What happens when DNA is methylated? And what happens when DNA is acetylated?

Answer 29

• Methylated DNA inhibits gene expression
• Acetylated DNA loosens chromosome structure, makeing the underlying genes easier to transcribe.

Question 30

What was found in 1997 by Meaney et al. in regard to epigenetics that laid base to a major breakthrough in neurosciences and psychology?

Answer 30

That variations in maternal care affect HPA-axis responses to stress in offspring, probably due to altered epigenetics. So parenting practises can profoundly shape child’s development and mental health.

Question 31

This lecture also discusses the article about rats and grooming and licking. Since the second lecture discusses this article in detail, I’ll ignore the article in this lecture.

Answer 31

ok

Question 32

What gene-environment interaction is there on the outcome of Anti-Social Personality Disorder (ASPD)?

Answer 32

There’s interaction between the MAO-A gene and childhood maltreatment

Question 33

What gene-environment interaction increases the chance of depression?

Answer 33

The interaction between a shorter allele of 5HTT and life stress

Question 34

What gene-environment interaction is there on adult depressive symptoms?

Answer 34

The interaction between child abuse and genetic polymorphism within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene.