Beyond nature versus nurture: The role of genes and biology Flashcards
True or False?
The ‘nature-nurture’ dichotomy is a false one, because it takes an over-simplistic view of our understanding of genetics and biology
True
What are the 4 main research methods that can examine the possible role of genes and biology in mental health difficulties?
1) Behaviour genetics
2) Molecular genetic association studies
3) Brain studies
4) Environment shapes brain-biology
What are the 3 main types of Behaviour genetics studies?
1) Family studies
2) Twin studies
3) Adoption studies
What are the 2 main types of Molecular genetic association studies?
1) Case control design
2) Family-based design
What are the 2 main types of brain studies?
1) Functional brain imaging
2) Structural brain imagining
What are the 2 main types of Environment that shapes brain-biology studies?
1) Gene-environment interaction
2) Epigenetics
Define Behaviour genetic studies
A field of research which studies variation among individuals on traits (e.g. a mental disorder) to distinguish the genetic contribution
A field of research which studies variation among individuals on traits (e.g. a mental disorder) to distinguish the genetic contribution
This is known as…?
Behaviour genetic studies
Behaviour genetic studies often calculate….?
A heritability estimate
What is a heritability estimate?
How much of the variation in a given trait (e.g. mental disorder) can be attributed to genetic variation
Which study calculates a heritability estimate?
Behaviour genetic studies
Which study involves conducting family, twin and adoption studies?
Behaviour genetic studies
Define family studies
Usually assess the first-degree relatives of an affected individual (‘proband’) for a mental disorder (MD), compared with a carefully selected control group
Usually assess the first-degree relatives of an affected individual (‘proband’) for a mental disorder (MD), compared with a carefully selected control group
This is known as…?
Family studies
The higher the heritability estimate, the more we think…?
The variation in a trait links to genetic variation
According to Gottsesman’s (1991) study, schizophrenia is ….?
Highly heritable but not all accounted for genetics
Who conducted a study with a range of relatives (and non-relatives) on schizophrenia?
Gottesman
According to Gottesman, does schizophrenia have a high genetic component?
Yes, it is heritable but genetics is not the only factor in schizophrenia
What are the 2 types of twin studies?
1) Monozygotic (MZ) - share 100% genetic commonality
2) Dizygotic (DZ) - share 50% genetic commonality
How is a heritability estimate calculated for twin studies?
A heritability estimate is derived from comparing MZ with DZ twins’ likelihood of being affected by the same disorder when one twin is affected
Define a concordance rate in twin studies
The % of cases in which both members of a twin pair have a particular attribute (e.g. a mental disorder)
Define adoption studies
A family study which involves the study of an individual’s traits and comparing them with the traits of their birth parents and adopted parents
What do adoption studies compare?
Compare the prevalence of the disorder (in adulthood)
What do adoption studies allow us to investigate?
Enables you to disentangle environmental influences from genetic influences
Who conducted a study on adoptees born to mothers with schizophrenia?
Heston (1966)
What did Heston (1966) discover about adoptees born to mothers with schizophrenia?
5/47 (10.6%) of the index group compared to 0/50 of matched controls were diagnosed with schizophrenia later in life
Simply = Adoptees born to mothers with schizo were diagnosed with schizophrenia later in life compared to adoptees born to healthy mothers
What are the 3 limitations of behaviour genetic studies?
1) Family and twin studies are likely to overestimate the genetic contribution
2) Unable to differentiate shared environmental factors
3) Twin studies involve mostly “Euro-Austro-American” (or White Western) samples
What are the limitations of twin studies?
They do not consider non-genetic psychological factors which affect MZ more than DZ twins
MZ twins are treated more similarly by parents, family members, peers and teachers, hence MZ twins have a similar rate of negative life events
What are the limitations of adoption studies?
Adoptions are relatively rare and often adoptees are placed in families resembling the biological family
Also locating the participants may be difficult as adoption is rare
Define Molecular genetic association studies
Studies at a molecular genetic level, focused on variants of specific (candidate) genes
Studies at a molecular genetic level focused on variants of specific (candidate) genes
This is known as…?
Molecular genetic association studies
Which study involves large samples with a particular mental disorder (index group)?
Molecular genetic association studies
Molecular genetic association studies involve small samples with a general mental disorder (index group)
True or False?
False
Molecular genetic association studies involve large samples with a particular mental disorder (index group)
Molecular genetic association studies involve large samples with a particular mental disorder (index group)
This index group is then compared with…?
Either those without the disorder or with an unaffected sibling
Molecular genetic association studies involve large samples with a particular mental disorder (index group)
Following a case-control design, what is the index group compared with?
Individuals without the specific mental disorder
Molecular genetic association studies involve large samples with a particular mental disorder (index group)
Following a family-based design, what is the index group compared with?
An unaffected sibling
What is a gene?
A gene is a segment of DNA that contributes to our characteristics.
How many genes do humans have?
20,000-23,000 genes, a copy from each parent
True or False?
Very few genes actually differ between people
True
What is a gene polymorphism?
A polymorphic gene has different variants, which (commonly) occur in the population
Different variants or forms of the same gene occur when ….?
More than 1 allele occupies that gene’s (fixed) position in the chromosome (as opposed to just one standard allele)
When more than 1 allele occupies that gene’s (fixed) position in the chromosome (as opposed to just one standard allele)
This is known as..?
Different gene variants (gene polymorphism)
True or False?
By ‘genetic differences’, we usually mean different variants of a gene
Simply = Different version of the same gene that might determine one’s characteristics
True
Can specific gene polymorphisms contribute to a mental health risk?
Yes
Many polymorphisms have been identified to increase risk for various mental disorders (sometimes called ‘risk alleles’)
Polymorphisms are sometimes called ….?
Risk alleles
Most research focuses on specific polymorphisms that….? List 2 conditions
1) Occur naturally in the population (i.e. they have no adverse effect on the individual)
2) May be associated with a mental disorder (coding for a protein involved in e.g. neurotransmitter synthesis or brain development)
What did Uher & Zwicker (2017) identify about genes?
There are 128 gene variants associated with schizophrenia, explaining 23% of the variance in schizophrenia
Uher & Zwicker (2017) identified 128 gene variants associated with schizophrenia
What did this explain?
23% of the variance in schizophrenia
What did Howard et al.’s (2019) meta-analysis of > 800k individuals identify about gene variants?
There are 102 variants associated with major depressive disorder (but many were also associated with other mental disorders)
True or False?
Mental disorders are monogenic
False
Mental disorders are polygenic
Mental disorders are polygenic
What does this mean?
Small effects of many genes acting together rather than just one singular gene influencing a particular disorder
Small effects of many genes acting together rather than just one singular gene influencing a particular disorder
This is known as…?
Polygenic
Rather than basing risk on singular genes, what do current, advanced studies do?
Studies now use polygenic risk scores
Recently, research has moved toward identifying a ……………. across ……………..
1) Common gene variant
2) Different mental conditions
What did Lee et al. identify about common gene variants in disorders?
Common gene variants in over 200k cases with 1 of 8 MDs
Based on strength of genetic relationships, Lee et al. organised disorders into how many clusters?
3
Based on strength of genetic relationships, disorders were clustered into 3 groups
What were they?
1) Mood and psychotic disorders
2) Disorders with compulsive behaviours
3) Early-onset neurodevelopmental disorders
What are the limitations of genetic association studies? List 2
1) Nearly four-fifths of DNA data comes from people of European ancestries (16% of the global population); not very diverse and generalisable
2) Within samples from European ancestries, effects are often very small with many failed replications
Genetic association studies are often very small with many failed replications. How come some results show positive effects?
False positive effects are likely due to very large samples
Effects are often very small with many failed replications due to samples mainly from European ancestries
Which type of study does this apply to?
Genetic association studies
Giannakopoulou et al. (2021)
From East Asian samples, there was limited evidence of transferability of evidence for the genes involved in depression, with only 11% of previously located areas implicated, and 2 novel genetic associations found
True or False?
True
A limitation of twin studies is that:
a) Environmental influence is unmeasured
b) Monozygotic twins are treated more similarly to each other than dizygotic twins
c) Shared environmental factors may be misattributed to the genetic contribution
d) All the above
d) All the above
What do brain imaging studies measure?
Brain structure (e.g. volume of the region) or functioning (brain activity while doing a task), comparing those with a mental disorder with those without
Measures brain structure (e.g. volume of the region) or functioning (brain activity while doing a task), comparing those with a mental disorder with those without
Which type of study does this apply to?
Brain imaging studies
What is a typical brain process? List 3 steps
- Perceives information
- Integrates it with past memories
- Responds emotionally and behaviourally
According to brain imaging studies, how do we know if a brain is dysfunctional/impaired?
Significantly heightened or reduced activation in a specific brain area in individuals with the mental disorder relative to controls
Significantly heightened or reduced activation in a specific brain area in individuals with the MD relative to controls suggests …..?
There’s a brain dysfunction/impairment or difference
What is the hypothalamus?
A small structure at the base of the brain that regulates hormones and is head of the HPA system
A small structure at the base of the brain that regulates hormones and is head of the HPA system
What is this called?
Hypothalamus
What happens in the hypothalamus that is characterised by depression and stress?
Dysregulation or hyperactivity of the HPA axis
Dysregulation or hyperactivity of the HPA axis is associated with…?
Depression (and stress)
True or False?
The hypothalamus is not involved in many signs of depression
False
The hypothalamus is involved in many signs of depression e.g. disordered day-night rhythm, lack of reward feelings, disturbed eating, sex, and cognition
What are frontal lobes?
Lower activation and smaller volume associated with major depression (linked with rigid thinking, impulsivity etc.)
Lower activation and smaller volume are associated with major depression (linked with rigid thinking, impulsivity etc.)
What is the term for this?
Frontal lobes
What does HPA stand for?
The hypothalamic-pituitary-adrenal (HPA) system
What happens when the hypothalamic-pituitary-adrenal (HPA) system responds to stressors?
It leads to the release of stress hormones (e.g. cortisol)
The hippocampus links perceptual systems with ….?
Memory (especially LTM)
How does depression link with the hippocampus?
1) Hippocampus links perceptual systems with memory (especially LTM)
2) Short-term memory (STM) transfer to LTM
3) Hippocampus encodes the emotional context of events from the amygdala
People with depression have increased hippocampal volume, especially if recurrent/early onset
True or False?
False
People with depression have reduced hippocampal volume, especially if recurrent/early onset
What did McQueen et al. discover about hippocampal volume and depressive episodes? List 2 main findings
1) Ps with depressive episodes had lower hippocampal volume only in multiple episodes (not first time having an episode) compared with control groups
2) Both depressed groups had poorer recollection memory
What is the main role of the thalamus?
Critical hub for relaying incoming sensory info for cognition and emotion processing
Info is sorted, integrated, edited, routed
Which part of the brain is this?
Critical hub for relaying incoming sensory info for cognition and emotion processing
Info is sorted, integrated, edited, routed
Thalamus
Reduced volume in schizophrenia may explain ….?
Changes in sensory experience and attribution
Young people with psychosis spectrum ‘symptoms’ also show ……… in an area of the thalamus
Smaller volume
Which part of the brain plays a role in memory’s links with perceptual and context info?
Hippocampus
Which part of the brain reduces in volume in psychosis?
Hippocampus
Which part of the brain generates emotional responses from the senses, especially
fear/anger?
Amygdala
Which part of the brain processes speech/sounds, emotions, and visual memories?
Temporal lobes
Which part of the brain experiences reduced activity linked with visual hallucinations?
Hippocampus
Which part of the brain has grey matter density and activation affected in individuals with
auditory hallucinations?
Temporal lobes
Which part of the brain experiences increased hippocampus-amygdala connectivity found in
paranoid schizophrenia?
Amygdala
Describe the hippocampus if an individual experiences psychosis
1) A role in memory’s links with perceptual and context info
2) Reduced volume of psychosis
3) Reduced activity linked with visual hallucinations
Describe the amygdala if an individual experiences psychosis
1) Generates emotional responses from senses, especially fear/anger
2) Smaller volume linked to psychosis
3) Increased hippocampus-amygdala connectivity found in paranoid schizophrenia
Describe the temporal lobes if an individual experiences psychosis
1) Processing speech/sounds, emotions, visual memories
2) Grey matter density and activation are affected in individuals with auditory hallucinations
What are the limitations of brain imaging studies? List 2
1) Causal mechanisms cannot be deduced as environmental factors linked with mental health difficulties are potential confounders
e.g. Research shows that lack of exercise/activity and accelerated ageing impact hippocampal volume
2) Neural ‘dysfunction’ / ‘abnormalities’ are often reported in brain imaging studies, implying a known absolute threshold for impairment, but this is not the case
Causal mechanisms cannot be deduced as environmental factors linked with mental health difficulties are potential confounders
e.g. Research shows that lack of exercise/activity and accelerated ageing impact hippocampal volume
What type of study does this limitation apply to?
Brain imaging studies
Neural ‘dysfunction’ / ‘abnormalities’ are often reported in brain imaging studies, implying a known absolute threshold for impairment, but this is not the case
What type of study does this limitation apply to?
Brain imaging studies
What do Gene by Environment (G x E) studies attempt to investigate?
Studies attempted to identify whether particular gene variants (risk alleles) increased mental disorder susceptibility when combined with adverse environmental factors
Studies attempted to identify whether particular gene variants (risk alleles) increased mental disorder susceptibility when combined with adverse environmental factors
What type of study is this?
Gene by Environment (G x E) studies
What do G x E studies propose about genetics and the environment and their influence on mental disorders?
Having a certain gene variant may increase mental health susceptibility in the face of environmental stressors
True or False?
Having a certain gene variant may decrease mental health susceptibility in the face of environmental stressors
False
Having a certain gene variant may increase mental health susceptibility in the face of environmental stressors
What did Caspi et al. do in their seminal G x E study?
1) Focused on three variants of a serotonin transporter gene (5-HTT) that have been linked to low mood
2) Two variants were significantly linked to increased risk for depression, only with multiple stressful life events
What were the limitations of Caspi et al.’s seminal G x E study? List 2
1) A seminal study, but failed replications (possibly due to multiple statistical corrections)
2) Cannot be sure that environmental factors are independent of the genes
What were the strengths/developments of Caspi et al.’s seminal G x E study? List 2
1) Studies use polygenic scores (rather than focusing on a single gene)
2) Few GxE interactions have been identified that predict polygenic risk scores of depression
The study of changes in how genes work (i.e. how they are expressed) induced by experience and environmental stress
This is known as…?
Behavioural epigenetics
Define Behavioural epigenetics
The study of changes in how genes work (i.e. how they are expressed) induced by experience and environmental stress
Simply = The study of how your behaviors and environment can cause changes that affect the way your genes work
Research has established that environmental influences can alter gene expression without any change to the DNA sequence
What does this suggest about our genes?
Our genes are not as fixed as we once thought
Define genotype
Genetic code itself (e.g. code associated with mood regulation)
Genetic code itself (e.g. code associated with mood regulation)
This is known as…?
Genotype
Define Phenotype
Gene expression (e.g. depressed mood and associated behaviours)
Gene expression (e.g. depressed mood and associated behaviours)
This is known as…?
Phenotype
Define epigenetic changes
Genes are expressed (‘turned on’) or silenced (‘turned off’), affecting how the cells read the genes
Genes are expressed (turned on) or silenced (turned off), affecting how the cells read the genes
This is known as…?
Epigenetic changes
DNA methylation alters the activity of the DNA, and this may be subject to environmental influence (e.g. stressors, hormones, diet, drugs…)
This is a prominent example of…?
Epigenetic changes
True or False?
‘Epigenetic switches’ control or coordinate much of the changes in our biology through the lifespan (e.g. metabolic, hormonal, neural)
True
Mice who had experienced early life stress showed suppression of the ‘dopamine expression’ gene
What happens when this gene expression is manipulated?
It reversed susceptibility to chronic stress (e.g. ‘anxiety-like’ behaviour and social interaction)
Studies have mainly involved mouse models due to ….?
Invasiveness
Several human studies have found a link between an epigenetic change (reduced methylation) in the ‘glucocorticoid sensitivity’ gene and the risk of post-traumatic stress disorder
True or False?
True
Several human studies have found a link between an epigenetic change (reduced methylation) in the ‘glucocorticoid sensitivity’ gene and the risk of post-traumatic stress disorder
What did this lead to?
A change in this ‘profile’ with narrative exposure therapy among Ugandan conflict survivors
What is the main benefit of behavioural epigenetic studies?
Studies may fill the gap between the relatively high heritability that behaviour genetic studies suggest, and the few gene variants strongly/moderately associated with a mental disorder
Studies may fill the gap between the relatively high heritability that behaviour genetic studies suggest, and the few gene variants strongly/moderately associated with a mental disorder
Which type of study does this apply to?
Behavioural epigenetic studies
Different research methods help us to understand the role of genes and brain biology brain in mental health conditions
True or False?
True
Research methods that help us understand the role of genes and brain biology brain in mental health conditions share 2 similarities. What are they?
1) The research methods generally support a transdiagnostic approach rather than singular disorders
2) The research methods may overinflate genetic contribution due to the role of environmental factors acting on both our genes and biology
True or False?
While studies suggest a substantial biological component, the genes and environment likely interact in complex ways that have not to date been measured using any singular method
True
How will future studies provide more insight to inform the intervention/treatment of mental disorders?
Future research should examine the genes with environment longitudinally, use mixed methods, and conduct replications across (non-Western) cultural groups
