Mental disorders Flashcards
Why can’t we assume that mental disorders are discrete/unitary diseases
-too much heterogeneity within diagnostic categories (ex: 2 ppl with the same disorder can have totally different symptoms)
-too much comorbidity across categories (being diagnosed with more than one mental disorders)
-continuity with normality (because of healthy normal groups variance, it is hard to establish “diagnostic lines”)
Why do gene variants that increase the risk of developing a psychiatric illness persist in the population? Why haven’t they been selected out?
Many of the gene variants associated with increased risk of mental illness regulate brain development and neural plasticity.
(neuronal migration in vitro, rules of plasticity, learning, memory, etc etc)
Their expression in the brain gives rise to altered patterns of neural activity throughout the brain. The problematic protein variants slightly alter the dynamic interactions of the thousands of proteins expressed in the brain across different cell types during development and maturation.
What are the components of the theory explaining the persistence of the genes that cause mental disorders? (explain)
Mutation-selection balance
→ mental disorder susceptibility genes are continually being selected out through evolution. But NEW mutation keep arising.
Inherited gene mutations
→mutations stick around for a long time. Brain is robust, allowing genetic variations to accumulate in the population if the individual mutations are not too severe
How do bad gene mutations affect the brain?
Do not directly cause a disease…they can collectively compromise the evolved interactions of everything in the brain, reducing the overall robustness of brain development and function
Why can identical twins have so much brain differences even if they have the same dna?
unavoidable randomness at the molecular level→ impacts how the brain develops
ex: main avec plein de crayons de couleur
What can body symmetry tell us about brain development?
Indicative of robustness of the genetic instructions
… clearer instructions
What does not correlate with body symmetry?
a. intelligence
b. physical health
c. physical attractiveness
d. symptom expression in schizophrenia
d.
What are the advices to maintain a healthy brain
Same as healthy body…(stay active, nutrition, stress and blood pressure reduction, good sleep habits, limit alcohol and avoid tobacco/drugs)
Define schizophrenia
Mental disorder characterized social withdrawal, disorganized thinking, abnormal speech, and an inability to understandreality.
Compare the different types of schizophrenia symptoms
Negative: the absence of behaviors (lost)
→ex: social withdrawal, reduced emotional expression, poverty of speech, and reduced motivation
Typically emerge 1st…then cognitive…then positive
Cognitive: disorganized and irrational thinking, deficits in learning and memory, poor abstract thinking, and poor problem solving
Positive: the presence of behaviors (not here before) →ex: delusions of persecution/grandeur/control, hallucinations
[Neurological: for example poor control of eye movements and unusual facial expressions]
How can we explain the high percentages of schizophrenia cases in male early adulthood vs female menopause?
Seemingly a correlation with hormone signaling.
In men, period associated with the end of myelination.(occipital–prefrontal btw)
How can we explain the high percentages of schizophrenia cases in male early adulthood vs female menopause?
Seemingly a correlation with hormone signaling.
In men, period associated with the end of myelination.(occipital–prefrontal btw)
→hypothesis: born with schizophrenia, reveals itself when myelination ends
→other one: pruning is too aggressive, too much synapses are destroyed
What is synaptic pruning?
Between early childhood and adulthood, elimination of useless synapses.
Name some believed environmental factors contributing to 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
What is the cause of schizophrenia?
environmental and genetic factors
What does heritability measure?
The fraction of phenotype variability that can be attributed to genetic variation
The amount of variation attributed to genetics→ the amount of variation that would be eliminated if everyone had the same genes.
(but even if no genetic variability, there is still the impact of environment )
How does the risk of developing schizo varies as we get further away from family bonds..
both parents 50%…one 13%…sibling 8%
Which factor, frequently comorbid with autism and intellectual disabilities, is an alleged cause of schizophrenia
rare gene copy number variations (duplicated or missing genes)..around 5% of cases are attributed to this
What is the seasonality effect?
A disproportionately large number of schizophrenic patients being born in February, March, April, and May
→suggests that something is happening in the womb few months earlier (ex: colder, ppl go inside and are more likely to get infections)
Name some factors affecting development in utero and leading to schizophrenia.
Season of birth, viral epidemics, population density, parental smoking
→Higher number of schizophrenic births in late winter and early spring if the temperature was lower than normal during previous autumn (keeps people indoors and favors transmission of viral illnesses)
→Three times more prevalent large cities >rural areas (transmission of infectious illnesses is facilitated by increased population density)
Monochorionic vs dichorionic twins
share one placenta vs individual placenta (identical twins either way)
How can prenatal environments of identical twins affect schizophrenia rates
Prenatal environments of monochorionic twins + similar than di
Concordance rate for schizophrenia ↑ for monochorionic twins
Name the behavioral and anatomical evidence indicating that abnormal prenatal development is associated with schizophrenia
Behavioral: Children who go on to develop schizophrenia display less sociability and deficient psychomotor functioning as kids.
Anatomical: Minor physical abnormalities are often seen in children who go on to develop schizophrenia →ex: partial webbing of the two middle toes and a high-steepled palate.
What is the main treatment for schizophrenia
Medication, often combined with psychological and social supports
How do antipsychotics/neuroleptics work?
Block dopamine D2 receptors
→relieve positive symptoms
In contrast with neuroleptics, what are the effects of dopamine receptors (ex: crystal meth)
Temporary activation on the positive symptoms of schizophrenia in ppl who do not have the disorder
What is the Dopamine Hypothesis
Excessive dopamine D2 receptor activity, particularly in the nucleus accumbens (striatum), underlies the positive symptoms of schizophrenia.
*some aspects of reinforcement learning is disrupted in schizophrenic ppl
*too much dopamine in the basal ganglia
What is the presumed cause of the negative symptoms of schizophrenia?
Hypo frontality: decreased activity of frontal lobes (+ dorsolateral prefrontal cortex, may relate to hypoactivity of local dopamine D1 receptors)
*too little dopamine prefrontal cortex
What are the effects of atypical antipsychotic clozapine
(in monkeys) simultaneously decrease dopamine levels in the striatum and increase dopamine levels in the prefrontal cortex
What are the goals of atypical antipsychotic
[made after 1990]. Do more than block D2 receptors
What are the effects of atypical antipsychotic aripiprazole
Partial agonist at the dopamine D2 and D3 receptors. It is thought to reduce dopamine receptor activity in the striatum (nucleus accumbens) but boost it in the prefrontal cortex.
What is a partial agonist?
Drug with very high affinity for a receptor but it activates it less than the normal ligand does.
can act as an agonist in regions of low concentration of normal ligand and as antagonist in regions of high concentrations
What is the autistic spectrum disorder?
Wide range of developmental disorders that are characterized by troubles with social interaction and communication, and by restricted and repetitive behavior.
What are the categories of symptoms that characterize autism
1st: trouble with social interactions and communication (verbal/nonverbal)
2nd: restricted/obsessive and repetitive behavior.
Autism is often a comorbid disorder. Name some common disorders diagnosed with autism
Intellectual disabilities, seizure disorder, sensory processing issues
Name some “typical” behaviors of autistic children
Not caring whether they are held or not; arch their backs when picked up
Call the kid’s name, does not consistently turn to look at you
Does not look in the eyes
What is the cause and heritability of autism?
genetic and environmental factors,
heritability around 70%
Many cases linked to spontaneous rare gene mutations that have severe effects
→ chromosomal abnormalities (ex: deletions, duplications or inversions)
Other cases associated with rare multigene interactions
→ ex: neurons don’t migrate to the right spot, cell types do not have the same numbers, synapses are different in terms of excitatory/inhibitory balance
Some cases linked with viral infections during pregnancy
How are the mild forms of autism called and what are the typical symptoms
deficient or absent social interactions and repetitive and stereotyped behaviors along with obsessional interest in narrow subjects.
don’t understand social cues and do not know what they are doing wrong
Explain the sex differences in autistic disorder
-heterogametic sexes tend to have more variance/variability in different aspects
-2:1 when autism + intellect disability
-7:1when high-functioning
Hypotheses for the cellular and molecular bases of early brain overgrowth include the following
- Altered neuronal migration during early gestation
- Abnormal formation of synapses and dendritic spines
- Overconnectivity in key brain regions
- Unbalanced excitatory–inhibitory neural networks
What do fMRI studies show in the brains of people with autism
marked abnormalities in brain activity, ex: little to no activity in the fusiform face area of autistic adults looking at human faces
How can autism be treated
goals: lessen impacts
- Intensive, sustained special education programs , behavior therapy early in life (self-care, communication, and life skills)
-Medications generally do not address the core symptoms, but often help reduce the irritability, inattention, and repetitive behaviors. comorbidity
examples
anticonvulsants (↑ GABA receptor activity)
antidepressants (↑ serotonin receptor activity)
antipsychotics (↓ dopamine receptor activity)
stimulants (↑ dopamine receptor activity)
Define affect and mood disorder
Affect: feelings/emotions
mood disorder: 1.bipolar 2.major depressive disorder
What is the difference between bipolar and major depressive disorder.
difference in mania
bipolar→ cyclical periods of mania and depression
MDD→ unremitting depression (or periods)..no alternation with mania
environmental factors
What is mania
[Episodes] characterized by sense of euphoria that does not seem to be justified by circumstances→ usually nonstop speech and motor activity
What can we use to treat bipolarity?
Lithium.
Once mania is eliminated, depression usually does not follow.
Unknown mechanism
What are the biological treatments for MDD
- Drugs that increase serotonin and/or norepinephrine signaling by inhibiting their enzymatic breakdown (e.g., monoamine oxidase inhibitors, MAOi) or by blocking their reuptake (e.g., tricyclics and serotonin specific reuptake inhibitors, SSRIs).
- Ketamine (NMDA glutamate receptor blocker)
- Electroconvulsive therapy (ECT)
- Deep brain stimulation
- Transcranial magnetic stimulation
- Vagus nerve stimulation
- Bright-light therapy (phototherapy)
- Sleep deprivation
How do tricyclic antidepressants work ?
Inhibits reuptake of serotonin and norepinephrine but also affects other neurotransmitters
How do SSRI work ?
Inhibit the reuptake of serotonin without affecting the reuptake of other neurotransmitters.
How do SNRI work ?
Specifically inhibits reuptake of norepinephrine and serotonin without affecting reuptake of other neurotransmitters.
What is the monoamine hypothesis?
Idea that depression is caused by insufficient monoamine receptor activity (serotonin, ne, dopamine)
(depression symptoms are generally not relieved by
What is the monoamine hypothesis?
Idea that depression is caused by insufficient monoamine receptor activity (serotonin, ne, dopamine)
(depression symptoms are generally not relieved by strong dopamine agonists–>research focus on ne and serotonin)
What could happen to someone with a low-tryptophan diet?
low-tryptophan diet and then a tryptophan-free amino acid “cocktail” lowers brain tryptophan levels and consequently decreases their synthesis of serotonin (5-HT). This tryptophan/serotonin depletion procedure can elicit a depressive episode in people susceptible to depression
(susceptible people )
What did functional imaging scans tell us about the role of the prefrontal cortex in depression?
One area of the anterior cingulate cortex (the subgenual region known as area 25) becomes less active after successful treatments
DBS
Describe the electroconvulsive therapy (ECT)
Used therapeutically to alleviate severe depression and bipolar disorder.
Seizures are electrically induced by applying brief electrical shocks to the head
In contrast to the delayed therapeutic effects seen with monoamine related treatments, the effects of other treatments (including ECT, lithium, DBS, VNS, and sleep deprivation) are more rapid. The seizures induced by ECT often reduce symptoms within days
What can explain the fact that total sleep deprivation has an antidepressant effect
a chemical builds up during waking hours that has some antidepressant effect, and it gets cleared away during sleep.
REM sleep deprivation also works, although more slowly, over the course of several weeks (similar to SSRIs)
Describe the sleeping habits of a depressed individual
Shallow, fragmented sleep. They tend to awaken frequently, especially toward morning.
In general, they spend more time in stage 1 sleep and less time in deep, slow-wave sleep (stages 3 and 4).
They also enter REM sleep soon after falling asleep, much earlier in the night in comparison to other people
Describe the types of anxiety disorders
General anxiety disorder: excessive anxiety and worry serious enough to cause disruption of their lives
Social anxiety disorder: excessive fear of being exposed to the scrutiny of other people that leads to avoidance of social situations in which person is called on to perform
Panic disorder: episodic periods of severe and unremitting terror. Includes symptoms such as shortness of breath, irregularities in heartbeat, and other autonomic symptoms, accompanied by intense fear
Agoraphobia: Fear of being away from home or other protected places
→ ((((Anticipatory anxiety: Fear of having a panic attack promotes anticipatory anxiety that sometimes leads to the development of agoraphobia)))
Describe anxiety disorder prevalence
12% people…around 2x more in females
What are the causes of anxiety disorders?
genetic + environmental (ex: childhood history) factors.
What parts of the brain are involved in anxiety disorders?
amygdala and prefrontal cortex
ex: Adolescents with generalized anxiety→ +activation amygdala, - activation ventrolateral prefrontal cortex when looking at angry faces
What is used to treat anxiety disorders
-Lifestyle change
- CBT
- Medication →ex: benzodiazepines
What are the 4 main groups of OCD symptoms
symmetry, cleaning, hoarding (every possession is valuable, cant throw things away ), forbidden thoughts (deviant nature, intrusive thoughts)
Compare compulsions vs obsessions
obsessions: recurrent, unwished thoughts
compulsions: behaviors seeking obsession-related anxiety
most adults realize that their behaviors do not make sense
What is the incidence of OCD cases
2%
Higher rates for women, but later diagnostic for them
What are the causes of OCD
genetic (50% of variability) and environmental factors (ex: child abuse, adverse events, even infections)
How is OCD treated
counseling, CBT, exposure-prevention
pharmacology : SSRIs
OCD can appear after brain damage. In what parts,,,ok tu comprends
basal ganglia, cingulate gyrus, prefrontal cortex
What brain activity particularity can we see in OCD patients
+ act frontal lobes and striatum
what is cingulotomy
cutting fiber bundle between PFC and anterior cingulate
What is ADHD
characterized by problems paying attention, hyperactivity, or difficulty controlling (inhibiting) behavior in an age-appropriate manner.
What are ADHD symptoms
reckless and impetuous behavior
act without reflecting
let interfering activities intrude into ongoing tasks
have difficulty withholding a response
How can we treat ADHD
counseling and ++ medication.
often stimulants that raise dopamine levels by blocking or reversing the dopamine reuptake transporter
+ dopamine-→this is important ok focus
What are the 2 branches of stress activation
- sympathetic branch of the ANS
- adrenal glands activation
What are the stress hormones
→→Glucocorticoids
Help to break down and convert proteins into glucose, make fats available for energy, increase blood flow, suppress secretion of sex hormones and stimulate behavioral responsiveness
Glucocorticoids have other physiological effects, too, some of which are not well understood. Almost every cell in the body contains glucocorticoid receptors, which means that few of them are unaffected by these hormones.
→→Cortisol
secretion of glucocorticoids is controlled by the hypothalamus. what are the steps leading to secretion
In response to stress, the hypothalamus starts a chain of events by releasing CRH/CRF (corticotropin-releasing hormone/factor).
CRH stimulates the pituitary to secrete ACTH (adrenocorticotropic hormone).
ACTH stimulates the adrenal gland to produce glucocorticoids.
