Lecture 21: Psychological Disorders l Flashcards
3 biological aspects of mental illnesses
they are heritable, common, and harmful to reproductive success
heritability of mental illnesses
20-80% of the variance in who has a given mental disorder is explained by genetics
the commonality of mental illnesses
the frequency of severe mental disorders is around 4%
harmfulness of mental illnesses to reproductive success
fertility rate is about half the national average
genetic studies about mental illness have discovered
that hundreds of common gene variants reflect a vulnerability to mental illness in general, not a specific disorder
psychiatric illnesses have high rates of
comorbidity (more than one diagnosis at the same time)
why are mental illnesses not discrete, unitary diseases?
there’s too much heterogeneity within diagnostic categories, comorbidity across categories, and continuity with normality
heterogeneity within diagnostic categories
two people with the same disease will have very different symptoms
comorbidity across categories
someone is more likely to get a second diagnosis than someone without a current diagnosis
continuity with normality
hard to draw fine lines to label diseases
similar symptoms can arise from _____
different neural circuits
many gene variants associated with mental illness regulate
brain development and neural plasticity. Their expression in the brain gives rise to altered patterns of neural activity throughout the brain.
mutation-selection balance theory
A popular theory for why mental illness mutations persist. Mental disorder susceptibility genes are continually being selected out through evolution but new mutations keep arising
inherited gene mutation theory
A popular theory for why mental illness mutations persist. The human genome has evolved to buffer environmental, genetic, and molecular noise. This robustness allows genetic variation to accumulate in the population if the individual mutations aren’t too severe
brain development mechanisms
Error-checking mechanisms and quality control efforts are put in place to guide proper brain development. But, much depends on chance
development of the two sides of the body
The two sides of the body develop independently from the same set of genomic instructions.
clear instructions for body development
the body should be symmetrical
unclear instructions for body development
the body should be asymmetrical
how to maintain a healthy brain
Stay active, physically and mentally
Eat well
Reduce stress, lower blood pressure
Maintain good sleep habits
Limit alcohol intake, avoid tobacco and hard drugs
two new treatment and prevention strategies for mental illness
- gene editing techniques that could be used in people or as part of IVF
- new pharmacological treatments that directly target intracellular signalling cascades rather than neurotransmitter signalling
schizophrenia symptoms
Characterized by social withdrawal, disorganized thinking, abnormal speech, and an inability to understand reality
% of people affected by schizophrenia
1%
how many people with schizophrenia don’t believe they have an illness
30-50%
schizophrenia onset
Increase in the late teenage years/the early 20s. Bump in females during menopause. Some connection to sex hormone signalling during puberty and menopause that affects brain functioning
types of schizophrenia symptoms
negative cognitive and positive
negative symptoms
the absence of behaviours (social withdrawal, reduced motivation)
cognitive symptoms
disorganized and irrational thinking, deficits in learning and memory
positive symptoms
the presence of delusions (hallucinations, delusions of control)
what symptoms of schizophrenia appear first?
Negative symptoms typically appear first, followed by cognitive symptoms, and positive symptoms many years later
neurological symptoms and schizophrenia
Many patients with schizophrenia also exhibit neurological symptoms, such as poor control of eye movements and unusual facial expressions and the illness is associated with subtle differences in brain structure
heritability
measures the fraction of the phenotype variability that can be attributed to genetic variation (the amount of variation that would be eliminated if everyone had the same genes)
cause of schizophrenia
environmental and genetic factors
estimates of schizophrenia heritability
80%
risk of developing schizophrenia if both of your parents have it or your identical twin has it
50%
risk of developing schizophrenia if one of your parents has it
13%
risk of developing schizophrenia if your sibling has it
8%
gene copy variations and schizophrenia
Around 5% of cases are attributed to rare gene copy number variations (duplicated or missing genes) which are frequently comorbid with autism and intellectual disabilities
environmental factors of schizophrenia
Mother’s nutrition during pregnancy
Mother’s stress during pregnancy
Certain infections (particularly during pregnancy)
Birth month
Being raised in a city
Childhood trauma
Social isolation
Perinatal hypoxia/brain damage
the seasonality effect
a disproportionately large number of schizophrenia patients are born in February, March, April, and May, especially if the temperature was lower than normal during the previous autumn
explanation for the seasonality effect
Perhaps because temperature causes people to go inside which increases the mother’s risk of getting diseases which increases the risk of the baby getting schizophrenia
schizophrenia in cities vs. rural areas
Schizophrenia is also about 3x more prevalent in people who live in the middle of large cities as compared in rural areas. This suggests the transmission of infectious illnesses is facilitated by increased population density
twins and schizophrenia
Some evidence suggests that the concordance rate for schizophrenia is much higher for monochorionic twins than in dichorionic twins, which suggests the prenatal environment is an important factor
monochorionic vs dichorionic twins
twins that share one placenta vs. have their own
behavioural evidence for abnormal prenatal development and schizophrenia
children who go on to develop schizophrenia display less sociability and deficient psychomotor functioning as kids
anatomical evidence for abnormal prenatal development and schizophrenia
minor physical abnormalities are often seen in children who go on to develop schizophrenia, such as partial webbing of the two middle toes and a high steepled palate in the mouth
main treatment course for schizophrenia
medication often in combination is psychological and social supports
antipsychotics/neuroleptics
drugs that have been developed that relieve the positive symptoms of schizophrenia. They typically block dopamine D2 receptors. (dopamine D2 antagonists)
what happens when non-schizophrenics take dopamine receptor agonists
they tend to temporarily elicit positive symptoms of schizophrenia
the dopamine hypothesis
excessive dopamine D2 receptor activity, particularly in the nucleus accumbens (stratum) underlies the positive symptoms of schizophrenia
do dopamine d2 receptors work for the negative symptoms of schizophrenia
no
what causes the negative symptoms of schizophrenia
hypofrontality, which is decreased activity of the frontal lobes, particularly the dorsolateral prefrontal cortex, which may relate to the hypoactivity of local dopamine D1 receptors.
what is associated with excess dopamine signalling in the straitum
positive symptoms of schizophrenia
what is associated with reduced dopamine signalling in the prefrontal cortex
negative symptoms of schizophrenia
dopamine in the brains of people with schizophrenia
too little dopamine in the prefrontal cortex and too much elsewhere
clozapine in monkeys
simultaneously decreases dopamine levels in the striatum and increase dopamine levels in the prefrontal cortex
Atypical antipsychotic medications:
Recently developed medications which aim to reduce both the positive symptoms and negative symptoms of schizophrenia. They typically influence the activity of several neurotransmitter receptors (beyond blocking the dopamine D2 receptor).
clozapine
First of the atypical antipsychotic medications. It blocks both dopamine D2 and serotonin 2A receptors.
aripiprazole
An atypical antipsychotic. It acts as a partial agonist at the dopamine D2 and D3 receptors. It is thought to reduce dopamine receptor activity in the striatum (nucleus accumbens) but boosts it in the prefrontal cortex
partial agonist
a drug with a very high affinity for a receptor but it activates it less than the normal ligand does
what type of drug is aripiprazole
a partial dopamine D2 receptor agonist
when do partial agonists act like agonists?
in regions of low concentration of normal ligands
when do partial agonists act like antagonists?
in regions of high concentration of normal ligands
some people argue that body symmetry is indicative of
the robustness of the underlying genetic instructions, which have to contend with environmental variation and molecular noise
what does body symmetry correlate with
intelligence, which overlaps with attractiveness and health. These gene variants are thought to be indicative of neurodevelopmental robustness
