schizophrenia paper Flashcards
(25 cards)
Biological Psychology &
Individual Differences
‘Risk factors for schizophrenia’
What is schizophrenia?
- For a (DSM 5.0) diagnosis of schizophrenia, an
individual should exhibit at least two of the
core symptoms - Symptoms must have been present for six
months and include at least one month of
active symptoms - Symptoms can be categorised as ‘positive’ or
‘negative’
Genetics as a risk factor for schizophrenia
- Evidence from family studies
- Evidence from twin studies
- Evidence from adoption studies
Environmental risk factors for schizophrenia
- Large-scale epidemiological studies have identified
many environmental factors associated with increased
schizophrenia risk, e.g.,: - Born in winter/early spring – reduced maternal
vitamin D - Born and raised in urban areas – more stress and
pollution - Whether people immigrated – higher stress and
exposure to new infections
Finding genetic risk factors for schizophrenia
- Family, twin and adoption studies have shown that
schizophrenia is highly heritable (70-80%) - Multiple approaches have been taken to identifying genetic
risk factors for schizophrenia over the years
Finding genetic risk factors for schizophrenia
- Early approaches, such as linkage studies and candidate
gene studies, assumed few genetic risk variants having a
large effect and were biased by our poor understanding of
biology and were largely irreproducible - We now know that genetic risk for schizophrenia is actually
largely conferred by the combined effects of many genetic
differences, mostly of small effect
Contemporary approaches to finding genetic
risk variants
- In order to identify genetic risk variants of small-moderate
effect, researchers have begun to compare the entire
genome (DNA sequence) of extremely large (>100,000)
groups of cases and controls - This has required multi-centre/national collaboration, and
the development of improved genetic analysis techniques - Scanning the whole genome means that studies are not
biased by our assumptions regarding underlying biology
Gene x environment interaction
- In a ‘diathesis model’, genetic and biological risk factors,
together with later environmental exposures, influence
disorder risk - Environmental factors may affect the activity of the genome
via ‘epigenetic marks’ e.g. DNA methylation - A number of epigenetic differences between the genomes of
individuals affected by schizophrenia and healthy controls
have been reported, but causality is difficult to prove
Individual differences in schizophrenia risk
A ‘mental health jars’ analogy
50 empty jars represent 50
individuals
Big and Small Marbles (to fill the
jars) represent risk factors.
Large marbles cause jars to fill
quicker and represent bigger
risk factors
Individual differences in schizophrenia risk
A ‘mental health jars’ analogy
5000 Small red marbles are
common genetic risk
variants (single nucleotide
variants, SNPs). They have SMALL
effects on risk
100 Large red marbles
are rare genetic risk
variants (copy number
variants, CNVs). They have
LARGE effects on risk
Individual differences in schizophrenia risk
A ‘mental health jars’ analogy
5000 Small blue
marbles are common
environmental risk
factors (e.g. everyday
stress). They have SMALL
effects on risk
100 Large blue marbles
are rare environmental
risk factors (e.g. childhood
mistreatment). They have
LARGE effects on risk
Individual differences in schizophrenia risk
- Sprinkle all the small red (small risk - genetic) and large red
(large risk - genetic) marbles randomly over the jars - Sprinkle all the small blue (small risk - environmental) and large
blue (large risk - environmental) marbles randomly over the jars - The extent to which the jar is eventually filled represents the
individual’s likelihood of presenting with the condition - Ultimately, the 50 jars will be filled to differing levels
(i.e. individuals have differing levels of disorder risk based
upon a combination of their genetic and environmental
exposures) - Rarely, jars will be completely full, and these represent
individuals who present with the condition
Polygenic risk scores
- From an individual’s DNA we can calculate their ‘polygenic
risk score’ (PRS) - An individual’s PRS gives us some idea of the extent to which
that individual is at genetic risk of developing a particular
condition (and is analogous to the extent to which their
‘mental health jar’ is filled with red marbles)
Polygenic risk scores
- The PRS is calculated by examining how many genetic risk
variants an individual possesses, and multiplying this by the
extent to which each increases risk - PRSs can be correlated with disorder-relevant brain and
behavioural measures in both healthy and affected
individuals e.g. how does an individual’s PRS scores for
schizophrenia correlate with relevant aspects of brain
structure, or with childhood behaviour?
Genetic risk predictions
- An individual’s DNA is easy to obtain e.g. from saliva, blood
or hair, and technology to analyse DNA rapidly and
accurately is becoming more accessible - Companies such as 23andMe can analyse your DNA sequence
if you send them a saliva sample using their collection kits
available in local pharmacies
Genetic risk predictions
- An individual’s DNA can be analysed from very early in life
e.g. DNA can be extracted from one cell of an 8-cell IVF
embryo, or from circulating foetal cells in the mother’s body - In the future every individual may have their DNA assessed
early in life to provide information on their likelihood of
developing an assortment of medical conditions
Schizophrenia risk prediction: good or bad?
Possible benefits
- May promote recognition of early symptoms and stimulate early (and
therefore more effective) treatment - Individuals at high genetic risk may moderate their behaviour accordingly
e.g. avoidance of unnecessary stress - More individuals with both ‘genotype’ (genetic) and ‘phenotype’
(brain/behavioural) data available will aid research into understanding
how genes confer risk for the condition - May increase democratisation of genetic knowledge and stimulate public
understanding of genetics
Possible problems
- Test may provide false reassurance, or may cause unnecessary
anxiety/stimulate unnecessary procedures - Implications for the child’s relatives, who may not want to know their risk
- Test results irrevocable, and may produce unwanted/unexpected
information e.g. regarding paternity - PRS provides limited additional information over and above existing
measures e.g. family history - Health advice to individuals is the same regardless of genetic information
availability i.e. eat healthily, don’t smoke etc. - Potential stigmatisation
- Possibility of having to disclose information to third parties e.g. insurers,
schools etc
Clinical insights from schizophrenia genetics
Genetic risk variants for schizophrenia tend to cluster in
genes important in immune, placental and synaptic function,
implicating abnormal function of these processes in disorder
risk
Treatments
- Antipsychotic drugs (act to block dopamine D2 receptors and
serotonin 2A receptors); side effects can include weight
gain and diabetes, motor problems, and reduced white
blood cell count (clozapine) - Psychosocial interventions e.g. family therapy or supported
employment
Bearden & Forsyth (2018) The many roads to psychosis: recent advances in understanding risk and
mechanisms.
positive symptoms
Hallucinations – Seeing, feeling and hearing things that aren’t there. Hearing voices is the most common type of hallucination
Delusions – Believing things that others don’t
Disorganised thinking – The things you say might not make sense to other people. You may switch topics without any obvious link
