Lectures 2 Flashcards
Acetylcholine is one of the main NT where?
In the periphery
Which other NT balances out ACh?
Epinephrine
What is parasympathetic overdrive?
When your parasympathetic system kicks in too strongly and you get negative effects fainting, dizziness)
When you are stressed, what NT goes up to compensate for the rising levels of epinephrine?
ACh
Which NT rises faster: epinephrine or ACh?
Epinephrine
What other major function does ACh do?
plays a role in muscle movement
What drugs block ACh?
Anticholinergic drugs
ACh has been used as war gasses. What are its effects?
Irreversibly increases the concentration of ACh in the body and results in a slow death
What are two main anticholinergic drugs?
Atropine and scopolamine
Which drug is better, atropine of scopolamine? Why?
Atropine
The difference between its LD50 and LD50 are higher so there is more room for error
What is an unintended side effect of atropine?
It greatly reduces inhibitions
What is another word for neurotrophins?
Growth factors
What do growth factors continue to do throughout life?
- Create myelin
- Grow dendrites and synapses
The brain works on a “use it or lose it” principal. What cell prunes unused synapses?
Macrophages (microglia)
What is the main role of BDNF?
Promote growth and synaptic plasticity, and maintaining synapses over time
Learning and levels of BDNF
Need to have BDNF in order to form the new synapses that are the neural basis of learning /memory
BDNF is particularly responsive to what types of events? What does that mean?
Stressful
It makes the events more memorable
Are all memories kept forever? Why?
No
If you had all memories it would be confusing for your mind
What is a disease that is related to not forgetting?
PTSD
In what situations does BDNF crash? What does this mean for making happy memories?
During chronic stress
You have no more BDNF so you will not remember the happy event (will continue to be sad)
FGF 22 is similar to what other molecule?
BDNF
Why do we need both FGF 22 and BDNF?
- Because it makes a redundant system (a back up)
- They work synergistically and symbiotically
- They kick in at different times
Can decreasing the amount of BDNF take away a memory?
No, the memory is already formed
What is EPO (Erythropoietin)
It is a drug that increases oxygen supply in the blood
–> Helps cells grow
Other than a growth factor, what can EPO be used for?
As an antidepressant (it increases BDNF)
- Used in conjunction with other treatments
In really basic terms, what is the role of the immune system?`
To know what is “me” and what is not
70% of the immune system is located where?
In the gut
Antigen:
A foreign particle
Pathogen:
A foreign particle that makes you sick
What is a neutrophil?
One of the first response immune cells
What is a macrophage?
It is the second immune cell that identifies and envelops the pathogen
How do macrophages identify particles?
After enveloping the partile, it send 2 “flags” up to its surface that mark:
- That it is active and has something
- Epitope (signature if the foreign particle)
Epitope:
Part of a particle that gets sent to the surface of a macrophage that identifies it
What types of cells are lymphocytes?
White blood cells
What are the different kinds of lymphocytes?
T-Helper Cells (Th1 & Th2)
B - Cells
Natural Killer Cells
What do Th1 cells do?
They respond to the epitope and get an immune response going is necessary
How does the Th1 cell decide if it needs to initiate an immune response?
It sorts through a “data bank” to see if the epitope is recognizable and/or harmful
What do Th2 cells do?
Stop the immune response
What cell do Th1 cells activate for an immune response?
T-Cytotoxic cells
What do T-cytotoxic cells do?
They will rapidly multiply to build an army against the pathogen
Why doesn’t the immune system kill off pathogens right away?
Because the pathogen is dividing at the same time so it can take time to win the battle
What are B-Cells
They rapidly multiply and attach themselves to the pathogen, disabling it
How do B-cells know what to attach to?
There are antibodies on its surface that recognize everything they encounter
How do B-cells attach to the pathogens?
It binds to the epitope and holds onto it
How do B-cells disable pathogens?
Once it binds, compliment factors will cause destructions
What are the chemical messengers of the immune system?
Chemokines/Cytokines
What do Th-regulatory cells do?
Keep the immune system from becoming over active
What do cytokines do?
They activate immune cells
- can act as growth factors
Macrophages release what kinds of pro-inflammaory cytokines?
IL-1beta
IL-6
Tumor necrosis factor alpha
What does IL-1beta do?
It is the strongest cytokine
- Produces the “sick” feelings (tired, sore muscles)
What does IL-6 do?
It has a much smaller effect
–Effects mood
Collectively, what do the macrophage’s cytokines do?
Will activate the T-helper cells, causing them to multiply
Which cytokines do Th1 cells release? What do they do?
IL-5
IL-18
» Cause t-cytotoxic cells to be released
What anti-inflammatory cytokines do the Th2 cells release?
IL-4
IL-10
What are microglia?
Macrophages in the brain
What do microglia do
- Sense damages cells
- Deal with dead cells and foreign particles
- Synaptic pruning
What can make microglia dysfunctional?
Seizures
Can cytokines cross the BBB?
Not easily
What happens to the BBB during stress?
it increases its permeability
The balance of cytokines
If levels are too high or low it can be neuro-destructive
Stress usually increases cytokines, but huge stressors do not result in toxic levels, why?
During stress cortisol is released and it suppresses the immune system (limits cytokine release)
What can be a danger of too much immunosupresstion when stressed?
It allows for illnesses to proliferate, like cancer
Physiological dose:
The amount of something under normal conditions (like baseline cortisol that limits cytokine release)
Pharmacological dose:
A high dose that alters the resting system (too much cortisol during stress limits immune system too much)
What effect does estrogen have on the immune system?
it can increase the release of cytokines
What diseases are more prevalent in women?
Depression and auto-immune disorders
If a woman has an autoimmune disorder, during what time in her life will the disease be suppressed?
During pregnancy because estrogen levels are lower
What type of immune response is best during an acute stressor, why?
A rapid response
It will be prepared to react quickly if you are injured
Cytokines = ______ stressor
systemic
What happens to the release of cytokines during a chronic stressor?
Originally cytokines go up, but eventually corticoid receptors down-regulate so cortisol can no longer put a cap in cytokines, and there is a damaging increase on cytokines»_space; can lead to disease
When does the immune system build up tolerance?
when it comes in contact with something regularly
Does the immune system always build up tolerance?
No
What 4 things dictate the quality of the immune system?
- How many immune cells there are at baseline/are they circulating
- Are they being released?
- Are they multiplying well?
- Are they good at killing
Why do diseases seem to appear suddenly but there usually it has been a long time coming?
Usually there has been an immune battle with no one winning for a long and then the disease finally takes over
Is there an immune response to a fetus?
Yes, the body does not recognize it as “me”
What hormone protects the baby from the mothers immune system and builds the baby’s immune system
CRH from the mother
Is antibody acquisition random? Why?
No, you get antibodies in a certain sequence
> Do not want to be protecting something that does not need protection
A big player in immunity is IGE. What can happen if it is over active?
It can activate mast cells which release histamine and you get have an allergic reaction or asthma
What can make allergies worse?
Stress
What is the hygiene hypothesis about why there are more allergies now?
We are too clean and are not exposed to as many things so we cannot build antibodies response towards it
What is an autoimmune disorder?
It is a hyperactive immune system that starts to attack the host
How does an autoimmune disorder choose where to attack?
There are different auto-antibodies, so it depends on which ones get activated
How does stress affect autoimmune disorders?
It makes a stronger immune response
Immune Surveillance Hypothesis
The immune system is always on the lookout for mutations and cancer cells
Not all mutations are bad. What is the example of the mutation in the inuit population
There is a polymorphism that all inuits have that protects them from getting heart disease even though they have such a high fat diet
What is the right to try?
when someone is dying, they have the right to try an experimental treatment
What are compliment cells?
They form a complex with B-cells that kill antigens
Which immune cell tries to stop a pathogen from getting onto an organ, and which one fights cells already in organs?
B-cell
T-cell
How do T-cells kill pathogens?
It attaches to the pathogen and pokes a hole in the particle to inject its own material which kills the pathogen
Once the kill switch on the immune system is activated, what bad thing can happen?
The immune system can start attacking the body
If our immune system is go great, why do we get sick?
It can take a few days before it gets fully up and running
|»_space; Some things impair the immune system like a lack of sleep or stress
How was the first small pox vaccine made?
There was a group of women (milk maids) who never got sick and someone figured out it was because they had come into contact with a less harmful cow pox and the women had built up antibodies. So as a vaccine, children were injected with cow puss
How are modern vaccines made
The virus is killed (heat or chemicals) but the outside remains with the epitope
How do vaccines work?
Your body will mount an immune response to the foreign particle and have memory antibodies to be able to quickly respond in the future
What is the secondary immune response?
The T and B cells are activated faster and they are stronger
How long does a normal vs secondary immune response take
Normal = ~4 days Secondary = ~2 days
Sepsis:
Blood infection
Virus vs bacteria replication
Viruses need a host to replicate
Bacteria can replicate outside of a host
How did Alexander Flemming discover penicillin?
By accident. He spilled some chemical on mould and saw that it died
What are unintended effects of penicillin?
People started to be less careful because there was a treatment. It got over used and now the bacteria is evolving
Antibiotic resistant bacteria
Antibiotics only kill 99% of bacteria, so the strongest1% stays alive and multiplies. Now there are new bacteria that are not treatable with antibiotics
Inevitability of a mass super bug pandemic
People live in more dense and more populated areas so disease can spread very quickly
Vaccine resistance
Some viruses have also started to mutate and are now resistant to the vaccines
What are some ways that viruses and cancer cells have started to trick the immune system?
They disguise themselves as body cells so they can go undetected
If you get the flu shot are you guaranteed not to get the flu?
No, there are many different strains and the doctors have to guess which one will be around the most but they do not always get it right
What is the primary activation of the immune system? what is it caused by?
Inflammation
Cytokines
Comorbidity and inflammation
Many diseases have an inflammation component, so they often occur together
Genetics of cancer
You can inherit genes that make you more susceptible to cancer, but you cannot get cancer from someone
What is on the end of DNA to keep it from being degraded during replication? What happens when it gets too short
Telomeres
When they degrade too much they are susceptible to mutations (cancer)
If the programmed death segments of DNA get disrupted, what can happen?
The cell may never die and they can become cancerous
Multi-hit hypothesis in cancer
You can have genes that make you susceptible to cancer, but by themselves they will not result in cancer, there needs to be another trigger to give you cancer
What factors along with genes can give a person cancer?
Other genes Foods bad lifestyle Belly fat No social support
Is it the severity of the hit or the number of hits that plays the most significant roll in your chances of pathology?
The number of hits
> multiple traumas are more impactful than one major trauma
Does stress cause cancer?
No studies have been able to find causality, but it makes cancer worse and it likely plays a role in the development
How does stress make cancer worse? (2 NT)
- Cortisol suppresses the immune system, so the body is less able to fight off the cancer cells
- Norepinephrine can stimulate cancer growth
How does norepinephrine help cancer grow?
It helps angiogenesis (developing small veins to the tumour) to feed it
What is the major limitation (2) in studying the effect that stress had on cancer development/
- Retrospective studies about how stressful life was prior to cancer diagnosis is coloured by current stressors
- Also cancer takes a long time to develop before it is detected, so you cannot know what is “before” cancer
Malignant vs Benign tumor
Malignant = can metastasize and it is harder to remove (no clear margins) Benign = does not metastasize, clear margins
What in terms of your weight makes chemo not work very well?
If you are over weight with lots of belly fat
Health span vs life span
Health span = number of years you were alive in good health
Life span = number of years alive
It is best to have cancer treatments that prolong what two spans?
Health span and life span
That cancer treatment increases health span but not necessarily life span?
CBT
What common notion do chemo and radiation operate on?
That cancer cells are multiplying at a faster rate so they need more food. You can poison the food to kill the cells
What is the main physical drawback from chemo and radiation?
healthy cells are killed alongside the cancer cells
if the cancer has come back do you use the same treatment again?
no, you usually use a more aggressive treatment
what are the 3 typical cancer treatments?
- Surgery
- Chemo
- Radiation
Why can’t chemo be used long term as a cancer treatment?
because the cancer cells develop a tolerance to it
What dose schedule can slow down tolerance?
Smaller doses over a long period of time
What was shown in the experiment with nude mice about cancer?
They did not have an immune system and they did not die from cancer
» but they died from other things so there is no conclusion about to role of the immune system and cancer
What are 2 alternative treatments that have are being used as cancer “treatments”
Managing diet
Mindfulness
What is the effectiveness of immuno-therapy for cancers/
20-30% effective
> many cancers that were not treatable before
Precision medicine
Use genes and bio-markers to target treatments for people
Precision medicine for people with cancers that respond to hormones
They can be treated with 80% success for people with the triple positive gene
Treatments with IL-2 and interferon alpha are really good at treating what?
Good viral and cancer killer
> Used for Hepatitis C and melanoma
If IL-2 and interferon alpha treatment is so effective, why is it not used often?
It makes people very ill
Half of people who use it get severely depressed
Why might IL-2 and interferon alpha cause depression?
Because depression is an inflammatory disorder so a heightened immune response would make it worse
How does injecting a virus into a tumour (viral therapy) help treat a tumour?
It will attract the immune system to the cancer cells and the immune system will try to kill the infected cells
What are immune check points?
There are certain points in a cell cycle where the immune system checks up on developing cells
How do cancer cells use checkpoints to grow?
They mask themselves to look like they are at a different stage in the cell cycle so the immune system does not check up on them
How do check point inhibitors work?
They do not allow the tumour to disguise itself so the immune system can kill the dysregulated cells
What is the success rate of check point inhibition therapy?
20-30%
How does CAR-T cancer therapy work?
- Isolate a person’s T-cells in a bottle
- Add the antigen and the T-cells will multiply
- Inject the T-cells back into the person for a heightened immure response
What is the major problem of CAR-T therapy?
It makes people so sick they want to die
What is the success rate of CAR-T therapy?
20-30%
Is the number of bacteria or diversity of bacteria most important?
Diversity
but number is also important
What is the enteric nervous system
the nervous system in the gut
What is the main NT of the enteric nervous system
Serotonin
Can the serotonin from the gut get into the brain?
No, it cannot cross the BBB
The vagus nerve is activated by what? (3)
Serotonin and bacteria (because they act on serotonin)
>also fungi
Dysbiosis
When there is an unbalance of the gut bacteria
If all illnesses involve the micro biome, what does that tell us
Not much because there is no specificity
Manipulating the microbiota
You can increase or decrease certain bacteria to result in different illnesses
What happens to your bacteria when you are stressed
The bacteria will start to die off
How has the protective nature of the microbiome been shown in mice?
If they are raised in a germ free environment and then exposed to a real environment, they will get sick. If you give them bacteria from a healthy person, the diseases will get better
How has it been shown that microbiome is implicated in “causing disease” in mice?
If you give a healthy mouse a poop transplant from a depressed human, the mouse will develop ulcers (stress)
Prebiotic vs probiotic
Prebiotic = food for bacteria that already exist Probiotic = a substance that contains bacteria to give you more bacteria
Are pre or pro biotics better?
Prebiotics seems to be better
What types of bacteria do antibiotics kill
All bacteria, good and bad
How can antibiotics be bad for an individual?
It kills the good bacteria so then potentially bad bacteria can take its place
What in our diet affects the microbiome?
Everything we eat affects it
Is the bacteria stable?
No it changes throughout the day (like when we eat)
What helps insulin take glucose into the cell when we eat?
IL-1
Bacteria can secrete what? Is it all the same type?
Cytokines
No, different types
How is the microbiome implicated in cancer
Some bacteria will secrete types of cytokines that will inactivate cancer treatments
When is the immune system the most active?
In the morning
> best time to have surgery or get cancer treatment
What is the adaptive nature of depression?
It is a signal to yourself and others that something is wrong
What brain area involved in physical pain is also active during depression?
Anterior cingulate cortex
How can mild depression help you?
Signals that something is not working and that there needs to be a change
What are the 2 main symptoms of depression (need to have one to be diagnosed)
- Sadness
2. Anhedonia
What are the other symptoms that you need to have some of to be diagnosed with depression? (5)
- Eat (more or less)
- Sleep (more or less)
- Lethargic
- Weight (loss or gain)
- Fatigue
What makes symptomology in depression difficult for diagnosis. What does that people for treatment
People can have different symptoms for the same illness but they will often be given the same treatment
What are the 3 main types of depression
- Melancholy
- Typical
- Atypical
What is melancholy depression
The most sever type, both sadness and anhedonia
- less food and sleep, lots of fatigue
> have positive neurovegetative symptoms
What is typical depression?
A less severe form of melancholy
- eat less but still eat some
What is atypical depression?
Sleep more, eat more, don’t show fatigue
> Eat when stressed
In what type of depression is the HPA axis and immune system more affected?
Atypical
People with atypical depression are hyper-responsive to external stimuli, what does that mean for compliments?
They will feel very good about themselves
What is dysthymia
A low grade of depression for at least 2 years that waxes and wanes
What is the ratio of depression in woman and men?
3:1
60% atypical
40% typical
Dysthymia is often associated with a personality disorder so it can be thought of as a ____
trait
People with dysthymia are often aversive, how does this affect their social life?
They lose friends, become more lonely and more depressed
What is double depression
When someone has dysthymia and also gets a major depressive episode
Do people with dysthimia seek treatment?
Often they do not because they have been dealing with it for so long
Cyclothymia
Depression that cycles dramatically
What are the two best predictors of depression?
- Rumination
2. Negative world view
With someone with double depression, what is the outcome of treatment?
They go back to being just dysthymic, that is there new normal
What is thought to be the cause of postpartum depression?
hormones and inflammation
What does Aaron Beck say is the cause of depression
Worked with learned helplessness so he says they have a schema of negativity about the world
How effective is CBT in treating depression?
50-60%
What did the yokes experiments with animals show about helplessness?
When the stressor is uncontrollable, the animal stops trying to do anything about it
What attributional style is most linked to depression?
Internal
Global
Stable
What are the problems of the learned helplessness theory in humans?
- Not everyone who have an uncontrollable stressor becomes depressed
- Does not consider biology
The drug reserpine does what?
it depletes monoamines
What did researchers find when they gave prisoners reserpine?
They got depressed
What was the issue with studying reserpine in a prison population?
Of course prisoners got depressed, they were in jail
What happens when the normal population is given reserpine?
They do not experience depression
What did the reserpine show us about the development of depression
it depends on both neurochemical and environmental factors
Is not having any control the worst thing?
No, having control and losing it is worse
When norepinephrine and ACh were looked at in the blood did they correlate with depression?
No
L-DOPA did not help cure depression, does that mean dopamine is not involved?
No, new drugs have shown that it is involved
Drugs for what NT work the best for treating depression?
Serotonin
What is the issue of monoamine oxidase inhibitors?
They cause a lot of side effects
Are SSRIs all they were stacked up to be?
No, they are not as effective as first thought
How many ineffective treatments does it take for someone to be diagnosed with treatment resistant depression
3
What therapy can work on people with treatment resistant depression?
Electro convulsive shock therapy
What are the results of electro convulsive shock therapy?
it works quickly and there are many changes in NT
What food should you not eat while on MAOs?
blue cheese
What are SNRIs (depression treatment)
Drugs that are broad spectrum re-uptake inhibitors
What was the theory behind SNRIs
If all the monoamines were increased it would have the biggest effect
What is a big problem of SNRIs
Monoamines are involved in lots of different systems so the drugs have many unintended effects
Why can taking anti-depressants be a bad thing?
Because they do not get at the root of the problem, so once you stop taking them you relapse
If antidepressants are not super effective, why take them?
Because not taking them could be worse
WHat are the results of testing antidepressants in animals?
It does not translate well to humans because humans are more complex than lab animals
CBT with antidepressants
It works pretty well. People get better coping skills so there is less rapid relapse
Mindfulness and antidepressants
Only works for people with a certain mindset
What are the 2 notions of mindfulness
- Think in the moment
2. Don’t be judgemental and be more accepting
What is the result of some people being naturally more mindful?
They are less likely to be depressed and they can be treated with mindfulness (combined with drugs)
WHat is the success rate of SNRIs
about 50%
What do the 5HT1A receptors look like in people with depression?
They are down regulated (or less sensitive)
WHat is the pattern of 5HTT in depression?
Disrupted
What are the 2 primary types of serotonin transporters?
Long and short
Short 5HTT
A person has a higher likelihood of becoming depressed
***Must be accompanied by a stressor
If you have the short rather than long 5HTT will you be depressed?
Not necessarily, it just makes you predisposed
|»_space; There is a gene-environment interaction
Often in science, what happens when you find part of the reason for something
You stop looking
If you alter levels of CRH does that affect depression?
No
> it is more related to anxiety
Balance of GABA and glutamate in depression
if either one is too high it can result in depression
Glutamate, immune response, and depression
If you have a pathogen, an immune response will be activated and glutamate will be released. This can cause sick behaviours that resemble depression
The “goldie locks range” of glutamate
The levels of glutamate need to be just right otherwise you get sick
What is ketamine
a drug that is a hallucinogen and gives an anesthetic like feeling
Ketamine blocks what receptors
the 2 glutamate receptors (AMPA and NMDA)
What are the benefits of using ketamine as an antidepressant
it works very quickly and in people who previously could not be treated
How long does ketamine work for?
5-7 days
The fact that ketamine treatment works so quickly, what notion changed about depression?
depression was not thought of as a personality type any more
If ketamine works quickly, why do SSRIs work so slowly
May take longer because it makes a series of chemical changes
» Untimately change glutamate
If you ___ levels of BDNF in mice they get depressed
lower
Is BDNF an effective treatment for depression?
Not very often
When it does work, it effects glutamate
What neurotransmitter initiates an immune response?
Norepinephrine
What are C-reactive proteins (CRP)
Substances that are released from the liver whenever there is an immune response
What do C-reactive proteins do?
Increase inflammation
Associated with a rise in cytokines
Have C-reactive proteins been found to cause depression
No conclusive supporting evidence
Stress & depression and illness susceptability
the more stressed or depressed you are, the more likely you are to get sick
The level of interleukin is related to the severity of what?
Depression
The cancer treatment interferon alpha can make people majorly depressed with what factors?
- history of depression
- short 5HTT allel
- female
- low tryptophan (serotinin)
- if you have a massive cytokine response
If you give what with interferon alpha it can help with the side effects?
Antidepressants
Is anxiety always bad?
No, it can be helpful in small doses
Anticipation of an event can create what?
Anxiety
People with elevated levels of CRH in their amygdala show what?
Anxiety profiles
CRH1 vs CRH2 stimulation in anxiety
CRH1 = when you stimulate you get a clear anxiety response CRH2 = when you stimulate you do not get an anxiety response
CRH1 is ____ symptoms
CRH2 is _____ symptoms
Cognitive
Somatic
Why can you feel anxious for no apparent reason?
when there are unconscious cues
How does the hippocampus cause place specific anxiety
it remembers that something bad happened there before and it lets you know that there could be trouble
Most phobias are ______
learned
What type of therapy gets rid of most fears?
Exposure therapy
|»_space; progressively face fear until it is no longer scary (extinction)
Why is anti-anxitey medication not helpful in exposure therapy?
Because you will not feel anxious during the exposure so you will not get to work through fear
Is there a treatment for generalized anxiety?
Nothing is very effective becuase it is such a complicated disease
The locus coruleus is over active during generalized anxiety, why is this bad?
because it keeps a person constantly vigulant
What happens if there is a dysfunction in the pathway between the PFC and the amygdala
The PFC might not be able to inhibit the amygdala and it will be over active
The microbiome has a large effect on NT, what 2 disorders can it produce?
Depression and anxiety
Anhedonia may be caused by what NT not working, why?
Dopamine
it is involved in the reward pathway
How can you induce depression?
By changing the microbiome
What 3 things can alter the microbiota?
Food
Stress
Antibiotics
What NT in the gut can affect the brain through the vagus nerve
Serotonin
When is IDO present?
When there is an immune response
What NT does IDO decrease, why?
Serotonin
by shunting the precursor tryptophan
IDO is converted into what?
Kyneurin
When there is dysbiosis what NT is most affected and in what brain region
Norepinephrine
Locus coruleus
Benzodiazepines (which affect GABA and Glutamate) are not used to treat generalized anxiety for what reason?
They can be addictive so they are not recommende for long term use
WHich drug is best for generalized anxirty
SSRIs
What is the effect of having one panic attack? Why
You are more likely to get another one
May have epigenetic effect
Why are benzodiazepines not used to treat panic attacks
Would need to take it every day and it is not good for long term use
Pure ____ can induce a panic attack
oxygen
What non-drug treatments are used to treat panic attacks? How effective are they
CBT and mindfulness
~50%
Is treatment for panic disorders better with drugs?
Not really, there is no additive effect
What are the two components of OCD
- Obsession = thinking about something and cannot let it go
- Compulsion = need to do something and cannot let it go
Does there need to be both obsession and compulsion on OCD
No but they often occur together
Obsession creates anxiety so you do what?
Act out the compulsion
What happens when you act out the compulsion?
Anxiety decreases so it is rewarding so you keep doing it
Son vs daughter with mom with OCD
Son: more likely to get Tourette’s
Daughter: more likely to have OCD
Does blocking dopamine and shutting down the reward centre work as an OCD treatment?
Not in humans
What two NT seem to work together to make OCD
GABA and dopamine
Yeda-Sentience =
Always on alert
What state is the brain in in people with OCD
It is always on alert
What do people with OCD need to find or else they go “crazy”
Security and safety
What maladaptive behaviours overlap with OCD
Gambling and addiciton
Is Tourettes learned?
no it is a compulsion
Compulsion/impulsivity is linked with low levels of what NT
Serotonin
ODC is comorbid with what?
Depression
What dose of SSRIs do you need to treat OCD
higher than in depression
All but what disorders can be seen in childhood
panic disorders
Trauma and phobia
A bad experience can lead to a phobia
Phobias are mostly learned but there is also a small ____ component
genetic
What type of therapy gets rid of most fears?
Exposure therapy
Who does exposure therapy work?
Through gradual steps that result in systematic desissitazation
WHat type of phobia cannot be avoided?
Social phobias
WHat fears do social anxiety include?
Fear that everyone is looking at them and that they are being judged
For people with social anxiety, how big is the cortisol increase before public speaking? Why?
300%
Because public speaking exposes you to humiliation and shame q
What are the different patterns of anxiety of experts and novices?
Novice: starts being nervous in the morning and it gets worse as the event nears
Experts: not nervous in the morning, a little right before, and then not at all during
WHat can happen if the social anxiety is bad enough?
A person will just stay in their house
Do drug treatments work for social anxiety ?
No
What is the best treatment for social anxiety?
CBT
But relapse is common
When does social anxiety start?
Usually in childhood, but it can start in childhood
WHat is often reported when adults get social anxiety
They say that they were shy but not overly shy as children
>Social anxiety probably learned
In people with social anxiety, what brain regions get very active in anticipation of a social situation?
Orbital frontal cortex (decision making) and anterior cingulate cortex
What does it take for a person to develop social anxiety?
One really strongly humiliating event can cause it
Example: you are a minority and someone discriminates against you, how do you protect yourself from social anxiety
Not internalizing the event and knowing it is directed at the group, not you personally. Identifying with the group can help you feel stronger
How many people get PTSD during their life?
8-10%
How much more do women get PTSD than men?
2x more
How did PTSD used to be viewed?
it was shameful
especially after the WW1, it was thought that they were weak
Now that trauma is more well understood and accepted, what is the big research question?
Why are some people not affected by the trauma
What use to be a requirement (but no longer is) of PTSD?
That a person encountere an abnormal stressor and that the event had to cause feelings of horror, fear and helplessness
In the DSM5 what is PTSD classified as?
A stress disorder
Now it is understood that PTSD can be induced by:
anything if your reaction is strong enough
Acute stress disorder:
the symptoms that you see right away after a stressor
If the symptoms of acute stress disorder last for more than __ weeks it is considered PTSD`
4
WHat are the 2 main PSTD symptoms?
- Hyper-arousal
2. Flashbacks (from a variety of cues)
What does not occur in people with PTSD?
Normal extinction of the trauma response
Does exposure therapy help treat PTSD?
No, repeated exposure makes it worse
What factors can make revisiting a traumatic memory therapeutic?
If it is done in a completely safe environment
What can memories be modifed?
When they are in short term memory (for the first time or when being remembered)
Why are things in long term memory easier to remember?`
Because there are lots of connections to it
What are 2 ways to disrupt a memory before it is formed?
ECT or give a drug that blocks protein synthesis (propanolol)
What is the goal when modifying traumatic memories
To change the valence of the memory
How is Eye-Movement-Desensitization Therapy proposed to work?
Moving your eyes takes a lot of mental effort so the brain is confused when recalling the memory so you are no longer able to tell if the memory is fearful
WHat are 2 NT involved in PTSD
CRH and epinephrine
Could one drug fix PTSD?
No because it involves so many different brain regions involved in vigilance (locus coereleus) and high arousal
WHat are 3 factors that are shared amongst many disorders/diseases?
- Alteration in synaptic plasticity and development of growth factors
- Inflammation
- Stress (predictive of later illness)
Hypertension:
High blood pressure
Any stress will always do what?
Affect the immune system and cause inflammation
What organ does norepinephrine affect during stress, what does it do?
Spleen
Causes cytokines to be released
What goes up when stressed?
blood pressure
If there is weakness in an artery and your blood pressure goes up as a result of stress, what can happen
you can have an aneurism
What is a brain bleed called? Is it fatal?
Hemorrhagic stroke
>almost always fatal
Hypertension increases your risk of what?
heart attack or stroke
What usually treats hypertension, but what is the issue with it?
Beta blockers (norepinephrine agonist) > Not very effective
What new drugs are more effective at treating hypertension
Ace inhibitors
What are the 2 best ways to prevent hypertension?
Eating right and exercise
What is a danger of using beta blockers?
You are more likely to bleed out during surgery
What are the 2 best predictors for heart disease?
- Depression
2. Inflammation
What is an index of the amount of inflammation in the body?
The amount of C-reactive proteins in the blood
Kyneurin is broken down into what?
A toxic substance
What is highly comorbid with heart disease
Depression
What is LDL
Bad cholesterol
What makes LDL dangerous
it builds up in veins and can cause a blockage
Why does LDL build up
Where there is a tear in a vein, it tries to repair it, but it will attract immune cells, and since LDL is sticky, they will build up in the vein
When do people notice a clogged artery
WHen it is 80% clogged
|»_space;too late
How does nitroglycerine help with clogged arteries?
It opens them up to allow for better blood flow
What surgery treats clogged arteries
Bypass surgery
Why is being overweight bad for heart disease?
Likely have more cholesterol and blood sugar
Why is excise good for you in terms of heart disease? (5)
- increases blood flow
- promotes neurogenesis
- strengthens heart muscles
- affects growth factors in the heart
- decreases inflammation
Chronic stress can result in what for heart disease
Increases blood pressure, which causes tears in veins and causes build up of plaques and choleterol
What can happen is a plaque gets disloged?
It can block an artery to the brain (stroke) or heart (heart attack)
> usually fatal
WHy do rich people live longer?
Because they can afford to live healthier
What makes low level jobs so stressfull
lots of responsibility but lack of control
What job stressor is the hardest on the heart?
Unfairness
Is type A personality related to heart disease?
Not really, only the hostility aspect
What type of hostility is related to heart disease?
Internal (self blame) but not external
Which personality type seems to actually be more predictive of heart disease and why?
Type D
Because they tent to ruminate, are pessimistic, and internalize problems
What are preventatives against heart disease?
- Lots of social support
- Anti-inflammatories (baby aspirin)
WHat is the best drug treatment for heart disease
“Cholesterol busters”
Hemorrhagic vs Ischemic stroke
Hemorrhagic = brain bleed Ischemic = blocked artery
Why is there continued brain damage after the stroke is over
There is a glutamate storm and an excess of cytokines, both of which are toxic
Why do many people get depressed after a stroke
There is lots of inflammation and also a loss of function
What is treatment for stroke?
Rehab
>can use video games
What happens when mice are raised in a germ free environment? How can you fix this?
-Hyper-anxious
-More prone to stress related diseases
»Fix it through a poop transplant from a healthy mouse
Can microbiome treatments work if you already have heart disease?
No because they damage is already done
What are the demographics of type 1 diabetes?
Equal male and female
Usually peaks at 14
Why do autoimmune disorders get worse over time?
There is sensitization
WHat cells, when damaged, no longer produce insulin
Beta cells (type 1)
What happens when there is a lack of insulin?
Glucose is not being takes up into cells and they starve
Why is it bad if there is too much glucose in the blood
it damages cells, especially the kidneys
Which diabetes is most stress reactive?
Type 2
what disease is a precursor to type 2 diabetes? what else is it a precursor for?
Metabolic syndrome
heart disease
What is metabolic syndrome
a build up of cholesterol and the heart cannot function properly
WHat dug is used to treat pre-diabetes?
Metformin
Why can’t cells with type 2 diabetes take in glucose?
Because the insulin receptors are not reactive
Why can’t massive amounts of insulin be given to treat type 2 diabetes
Even though it works, insulin has other affects on growth factors
Why do some women get gestational diabetes?
They are usually already more susceptible and it is caused by hormonal changes
What does gestational diabetes often turn into?
Type 2 diabetes
What makes studying illnesses hard?
Animal models are not perfect and we cannot use humans like lab rats
Innate vs acquired immunity
Innate = immune system that developed as a fetus that you are born with Acquired = immune system that you build over life
What is adaptive immunity
Immunity that is adaptive (can be innate or acquired)
