Emotional Behavior Flashcards
(152 cards)
1
Q
Psychologists generally agree that emotion has components including ________(“this is a dangerous situation”), __________ (“i feel frightened”) ,
____(“run away now”) and _________(increased heart rate and heavy breathing)
A
cognition, feeling, action , physiological changes
2
Q
Sympathetic nervous system
A
stimulates certain organs such as the heart, and inhibits others such as the stomach and intestines: it stimulates organs important for vigorous fight or flight activities, inhibiting vegetative activities that can wait until later
3
Q
Parasympathetic nervous system
A
The parasympathetic nervous system increases digestion and other processes that save energy and prepare for later activities
4
Q
Nausea in terms of nervous system
A
Nausea is associated with sympathetic stimulation of the stomach (decreasing its contractions and secretions) and parasympathetic stimulation of the intestines and salivary glands
5
Q
pure autonomic failure
A
Uncommon condition called pure autonomic failure output from the autonomic nervous system to the body fails, either completely or almost completely; heartbeat and other organ activities continue but the nervous system no longer regulates them
They do not respond to stressful experiences with changes in heart beat, blood pressure, or sweating
They report having the same emotion as everyone else but they do have difficulty identifying what emotions a character in a story would probably experience
They say they feel their emotions much less intensely as before the autonomic failure
The implication is that feeling the body change is important for feeling an emotion
6
Q
Panic disorder
A
characterized by frequent periods of anxiety and occasional attacks of rapid breathing, increased heart rate, sweating and trembling (i.e. extreme arousal of the sympathetic nervous system; important part of the disorder is frequent fear of the next panic attack
more common in women than men and far more common in adolescents and young adults than in older adults
abnormalities in the hypothalamus and not necessarily the amygdala
Panic disorder is associated with decreased activity of the neurotransmitter GABA and increased levels of orexin
7
Q
orexin
A
(associated with wakefulness and activity)
Orexin is also associated with anxiety, drugs that block orexin receptors block panic responses
8
Q
Panic attack
A
when people gasp for breath, worry that they are suffocating and experience great anxiety
9
Q
Although emotional feelings correlate strongly with arousal of the autonomic nervous system, no particular emotion is consistently associated with ………….
A
a distinctive pattern of autonomic activity
10
Q
behavioral activation system (BAS)
A
Activity in the left hemisphere especially its frontal and temporal lobes called behavioral activation system (BAS) marked by low to moderate autonomic arousal and a tendency to approach; characterize happiness or anger
11
Q
behavioral inhibition system (BIS)
A
Activity of the frontal and temporal lobe of the right hemisphere is associated with the behavioral inhibition system (BIS) which increases attention and arousal, inhibits action, and stimulates emotion such as fear and disgust
12
Q
People were quicker and more accurate at identifying happy faces when the information went to the ____hemisphere; and had an advantage in processing sad or frightened information when the information went to the___ hemisphere
A
left, right
13
Q
people with greater activity in the frontal cortex of the __ hemisphere tend to be happier, outgoing and more fun-loving
People with greater__ hemisphere activity tend to be socially withdrawn, less satisfied with life, and prone to unpleasant emotion
A
left, right
14
Q
Seasonal affective disorder (SAD)
A
Depression that occurs during a particular season such as winter, SAD is most prevalent near the poles where winter nights are very long
People with seasonal affective disorder have phase delayed rhythms
Many people with SAD have a mutation in one of the genes responsible for regulating the circadian rhythm
Treat SAD with very bright lights 2500 lux for a couple hours each morning or even brighter lights for a shorter amount of time which resets the circadian rhythm
15
Q
Alcohol and Anxiety
A
Alcohol also reduces anxiety through effects on GABA receptors
Alcohol promotes the flow of chloride ions through the GABAa receptor complex by binding strongly at a special site found on only certain GABA receptors
16
Q
Experimental drug known as Ro15-4513 is particularly effective in blocking the effects of alcohol on GABA receptors
A
Ro15-4513 blocks the effects of alcohol on motor coordination, its depressant action on the brain and its ability to reduce anxiety
17
Q
People with the strongest ______ are the least likely to make the “logical” decision to kill one and save 5 others
A
autonomic arousal
18
Q
_____________ becomes active when they compare the utilitarian and emotional aspects to make a decision
A
ventromedial part of the prefrontal cortex
19
Q
damage to the ventromedial prefrontal cortex
A
more selfish with earnings and trust others less and show little concern for others; symptoms are poor decision making and impulsive behavior
20
Q
Frontotemporal Dementia
A
(frontotemporal lobe degeneration) in which parts of the frontal and temporal lobes of the cerebral cortex gradually degenerate
often damage includes ventromedial prefrontal cortex and orbitofrontal cortex: important for evaluating possible rewards are also important for interpreting and evaluating other people’s emotional expression
People with damage of this type do not recognize or respond to others reactions, including reactions of distress and therefore show little empathy or concern
People with frontotemporal dementia also show little interest in how others perceive them; they neglect personal hygiene and fail to show embarrassment
21
Q
limbic system
A
includes the forebrain areas surrounding the thalamus, Cerebral cortical areas; some are subcortical, some in prefrontal cortex, amygdala
Critical for emotion
22
Q
Amygdala
A
The amygdala is important for learning to fear a particular stimulus
Input from sensory systems including vision and hearing goes to the lateral and basolateral areas of the amygdala, relay information to the central amygdala which combines it with pain and stress information that it received from the thalamus
Learning a fear strengthens synapses at several of the connections along this route
One part of the amygdala controls changes in breathing, another controls avoidance of potentially unsafe places, and another controls learning which particular places are safest
The path from the amygdala responsible for freezing in the presence of danger is separate from the path controlling the changes in heart rate
Amygdala responds most strongly when facial expression is a bit more difficult to interpret
23
Q
bed nucleus of the stria terminalis
A
Long term generalized emotional arousal depends on a brain area called the bed nucleus of the stria terminalis; the stria terminalis is a set of axons that connect the bed nucleus to the amygdala
24
Q
fMRI show that human ______ responds strongly when people look at photos that arouse fear or at photos of faces showing fear or anger
A
amygdala
25
Anxiety depends on _______________ that help people cope with threatening information
amygdala and cortical areas
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reappraisal
an effective way to cope is reappraisal- reinterpreting a situation as less threatening
Reappraisal and similar methods of suppressing anxiety depends on top-down influences from the prefrontal cortex to inhibit activity in the amygdala
People with stronger connections between the prefrontal cortex and the amygdala tend to make more use of appraisal and tend to feel less anxious
27
damage to the amygdala and surrounding areas at least in one hemisphere are impaired in what ways?
can classify photos as pleasant or unpleasant as good as anyone else and have no problem with the cognitive aspect of unpleasant emotions but they lack much of the feeling aspect
28
urbach-wiethe disease
accumulate calcium in the amygdala until it wastes away; extensive damage to the amygdala without much damage to the surrounding structures; impaired at processing emotional information and learning what to fear
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function of amygdala
important for imagining the fear and thing about danger
amygdala is responsible for detecting emotional information and directing attention to it
Eyes are particularly important for recognizing fear. People express happiness with the mouth but they express fear mainly with the eyes
30
state the testing parameters that are very important for aggressive behavior
species/ strain (e.g. mice or rats, different types of rats, etc)
Resident-intruder test
Neutral arena test
Time of day/ photoperiod (short photoperiod- non reproductive winter condition; long photoperiod- reproductive period)
Sex of subjects (males do show more aggression in rats; in hamsters females are more aggressive; generally females are aggressive in defense of pups)
Size of subjects (interaction lasts longer between opponents if they are closer in size)
Size of intruder
Bedding and diet: some bedding have phytoestrogens which alter hormones from plant compounds
Social history
Winner effect, if they won before, more likely to win again
Social defeat; if they lost before, more submissive behavior which can be long-lasting (changes in brain and behavior)
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first attack enhances home hamster’s readiness to attack against any intruder for the next 30minutes or more is due to...
During that period, activity builds up in the corticomedial area of the amygdala; it increases the hamster’s probability of attacking
32
With almost anything in psychology, individual differences in aggressive, violent, or antisocial behavior depend on both _____________
heredity and environment
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aggression and T
Young adult men who have highest T levels, have the highest rate of aggressive behaviors and violent crimes; T, esp a sudden burst on T facilitates aggressive, assertive, dominant behavior
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Hormone________inhibits aggression; adrenal gland secretes cortisol during periods of stress and anxiety and
_____ leads to cautious behavior that conserve energy
cortisol
| Anxiety increases cortisol levels, anger decreases it
35
Studies with both male and females of several ages have found that a combination of __________increases aggressive and risky behaviors
Low _____ mean decreased fear of harmful consequences, whereas ___increases the expected pleasure or gain; opportunity for attack is often seen as rewarding
high T and low cortisol, cortisol, T
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cfos?
transcription factor: regulates transcription of various other genes(cell nucleus)
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aggressive encounters increased activity in the....
amygdala including medial amygdala (dorsal part of the amygdala towards the front of the brain)
Lot more activation in medial amygdala and a lot less activation in the preoptic area
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circuit for aggression includes areas
anterior hypothalamus, periaqueductal gray (PAG) and the orbitofrontal cortex (above eyes- provides inhibition action in the medial amygdala)
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orbitofrontal cortex (OFC)
break on aggression, stress weakens break (disinhibition of aggression under chronic stress) and accelerators
40
what is serotonin turnover
When neurons release serotonin, they reabsorb most of it and synthesize enough to replace the amount that was washed away. The amount present in neurons remains fairly constant, but if we measure the serotonin metabolites in the body fluids, we gauge the turnover, the amount of neurons released and replaced.
Isolating male mice for 4 weeks increased their aggressive behavior and decreased their serotonin turnover (5-HIAA (serotonin metabolite levels)) which increase aggressive behavior
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how do researchers measure amount of serotonin turnover?
concentration 5-hydroxyindoleacetic acid (5-HIAA) serotonin’s main metabolite in the cerebrospinal fluid (CSF); measuring the amount in blood or urine is simpler but less accurate alternative
42
Impulsiveness and aggressive behavior are associated with low _____release
serotonin (5-HT)
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serotonin
monoamine that once released into the synaptic cleft can be metabolizes or reuptake mechanisms
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microdialysis
look at serotonin and its metabolite- to get extracellular fluid for sampling- microdialysis- (dialysis- filter out toxins that kidney would normally do, similar idea; method of filtration; microdialysis DOES NOT filter toxins) microdialysis probe- has tubing that goes through the probe and then we can pump liquid through probe down to brain, opening at end of probe to exchange fluid or enter fluid to collect fluid (microdialysate= liquid pumped in + extracellular fluid) to measure components of the fluid from brain area of interest such as the amygdala to get an idea about compounds in the extracellular fluid such as serotonin and/or metabolites levels in extracellular space in a certain area
45
environmental factors associated with increased violent tendencies:
Witness violence or victim of violence in childhood strong predictor of committing a violent act
Living in a violent neighborhood
Environmental exposures (e.g. lead): more large scale wipe-spread changes in neural development
46
Genetic Factors in Violence
Genes influence violent behavior in many ways, including autonomic arousal and impulsivity
Attempts to find a strong link between aggression and a single have generally failed
47
MAOa (monoamine oxydase A)
degrades/metabolizes monoamines such as serotonin, dopamine, norepinephrine, enzymes in synapse that degrades monoamines (other monoamines are metabolized too; not specific to serotonin): MAO
After a neuron releases serotonin, dopamine, or norepinephrine, most of it returns to the neuron via reuptake; enzyme MAOa breaks down some of it, preventing accumulation of an excessive amount
48
Version of gene (short form) with low MAO on behavior
severe mal-treatment, show much more aggressive behavior; But there may be benefits in the short form of the MAOA gene as it persists in the population
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Version of gene (long form) with high MAO on behavior
severe childhood mal-treatment, still more resilience to aggressive behavior (less aggressive behavior)
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What's the effect of childhood mal-treatment on aggressive behavior in adulthood?
Depends on genetic makeup
51
What’s the effect of MAOA genotype on aggressive behavior?
Depends on early childhood experiences
52
Hormone experiment 1849
| Endocrine experiment
Castrated then grown up into capans (look like hens, no aggressive or sexual behavior)
Early hormones have important effects on behavior and morphology
Switch testes- normal male development
Testes reimplantation- normal male development
The testes grew new vascular but the nerves did not connect
Testosterone from testes regulates male aggression and sexual behavior in bloodstream
53
Male Song sparrow study; how did they reach the conclusion that there was no clear role of the gonad on aggression and that Testosterone is dimmer switch, gradually changes levels of behavior rather than turning it on completely?
Spring is good time to reproduce: high levels of aggression and testosterone
Testes and ovaries enlarge in the spring time while during non-breeding season, they will decrease in size
They are still aggressive during winter even though testosterone levels are low and testes are regressed
No clear role for gonads
in non-breeding season, plasma T and estradiol levels are not detectable (plasma = blood without the cells)
In non breeding season, no effect of castration on territorial/aggressive behavior
Dissociated pattern of aggressive behavior- aggressive behavior is not affected by testosterone
54
which brain regions have lots of aromatase in the non breeding song sparrows?
Bed nucleus of the stria terminalis (BNS), POA (preoptic area), ventromedial hypothalamus (VMH), MCN (more caudal in brain- important for song perception, similar to medial hypothalamus of mammals) contains lots of aromatase
55
_____regulates male aggression in the breeding season of song sparrow
Aromatase
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fadrozole FAD
aromatase inhibitor
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effects of fadrozole on non breeding song sparrow
10 days after treatment:
Reduces number of songs, number of flights around cage: when simulating a cage intruder
Decreases the time they spend in close proximity to the intruder
Giving back estradiol restores all behaviors
Giving back estradiol; good because we have taken away estradiol and by giving it back will restore behavior: the effects from fadrozole is due to the effects of reducing estradiol as restoring estradiol restored behavior
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Androstenedione
turned into estrone (another estrogen) by aromatase
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source of estrogens:
DHEA (steroid that has anti glucocorticoid effects)
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DHEA
(does not have their own receptors) is “inert” and secreted by adrenals & converted into active sex steroids (T and estradiol) within target tissues
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what are the 3 ways that steroids exert effects?
1. Bind to membrane receptors, like neurotransmitters, exerting rapid effects
2. They enter cells and activate certain kinds of proteins in the cytoplasm
3. They bind to receptors that bind to chromosomes where they activate or inactivate certain genes
62
Can brain convert DHEA into T or estradiol in brain:
| To test this:
Take brain tissue and homogenize it in test tube, add radiolabeled DHEA to look at production of radiolabeled androgens and estrogens
63
what is 3 beta - HSD? and how do levels of this enzyme differ in breeding and non-breeding season?
critical enzyme that converts DHEA into androstenedione, which in increased (up-regulated) in non-breeding season and lowest in the breeding season; in the breeding season there is plenty of T and estradiol so not need enzyme
3 beta - HSD up-regulated when local steroid production in brain is need during non-breeding time
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in non breeding season, how do we see T and E2 in the brain but not the blood?
B: adrenal gland secreting DHEA into blood which then goes up to brain then converted into T and estradiol locally so do not see steroids in blood but present in brain
C: adrenal and testes are not involved at all; neurosteroid with lots of cholesterol in the brain which then converts into progesterone to DHEA to T and E2 in specific brain areas
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how is aggression promoted in breeding season?
spring time when breeding the male testes are enlarged that secrete T into blood which reaches the brain and is converted into estradiol by aromatase in specific regions which then promotes aggression
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why might localized T in the brain be helpful?
T has a lot of effects throughout the body, they want to certain effects of T but not others; by not producing in testes and in circulating vasculatory system, effective way to localize effects of T
T is known to suppress immune system, reduce fat store; but in winter, they want fat stores so that they can survive without food for a bit
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Male aggression is ultimately dependent on ______
estrogens
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examples of acute non-specific nocuous agents for testing
exposure to cold, surgical injury, production of spinal shock (transicion of the cord), excessive muscular exercise, or intoxications with sublethal doses of diverse drugs (adrenaline, atropine, morphine, formaldehyde, etc.)
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A syndrome produced by diverse Nocuous agents
Symptoms are independent of the nature of the damaging agent or the pharmacological type of the drug employed, and represent rather a response to damage as such
This syndrome develops in three stages:
during the first stage, 6-48 hours after the initial injury, one observes rapid decrease in size of the thymus, spleen, lymph glands, and liver; disappearance of fat tissue; edema formation, especially in the thymus and loose retroperitoneal connective tissue; accumulation of pleural and peritoneal transudate; loss of muscular tone; fall of body temperature, formation of acute erosions in the digestive tract (ulcers), particularly in the stomach, small intestine, and appendix; loss of cortical lipoids and chromaffin substance from the adrenals
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Hans Selye defined “stress” as
non-specific response of the organism to any demand made upon it
internal perception of the external event, occurring within brain: could contextualize in brain to not become a big stress response
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General adaptations syndrome by stress:
threats (“stressors”) to the body activate a general response to stress
Alarm stage: increased sympathetic nervous system activity (acute)- epinephrine, norepinephrine
Resistance stage: sympathetic response declines; adrenal cortex continues releasing corticosterone/cortisol and other hormones to promote alertness from adrenal gland
Exhaustion stage: occurs after chronic, prolonged stress; individual no longer has energy to sustain responses; individual does not have capacity to cope with stressors
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acute stress for humans and zebras
Acute stressor for zebra: predator attack, storm passing, long drought (chronic stressor with more chronic stress response)- disease can come about from prolonged chronic stress response
Acute stress for humans: exam, giving speech, having spouse or loved one with disease (chronic stressor results in chronic stress response into disease like symptoms)
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startle reflex:
auditory information goes first to the cochlear nucleus in the medulla and front there directly to an area in the pons that commands tensing the muscles esp the neck muscles; tensing the neck muscles is important as the neck is vulnerable to injury
Information reaches the pons within 3-8ms after a loud noise; full startle reflex occurs in less than two-tenths of a second
Current mood or situation modifies tour reaction; your startle reflex is more vigorous if you are already tense
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PTSD and the brain areas important for it
frequent distressing recollections (flashbacks) and nightmares about traumatic events, avoidance of reminders of it, and vigorous reactions to noises and other stimuli
People with post traumatic stress disorder (PTSD) show an enhanced startle reflex
Most victims of PTSD have smaller than average hippocampus
Severe stress can impair function in the hippocampus and sometimes cause shrinkage
People with a smaller hippocampus tend to rate their experience more stressful
Recovery of PTSD did not increase the size of the hippocampus but people with the smallest hippocampus were less likely to recover quickly
Amygdala important for emotional processing is essential for the extreme emotional impact that produces PTSD
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Sympathetic nervous system response to stressors
“Flight” or “fight” responses
Acute, transient stressors - pass quickly
Generally useful and adaptive
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HPA axis response to stressors
Chronic prolonged stress
Qualities around unpredictability, we do not have control: COVID
Acute stressors prolonged could become a chronic stressor
Problematic in the long term
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Acute stress response
“Fight” or “flight”
Increases availability of energy- blood glucose
Increased oxygen intake,
Increased blood flow to muscles; blood vessels going to muscles dilate to transport more glucose and oxygen
Inhibition of digestion, growth and repair, reproduction, pain perception
Altered immune function: immune cells leave blood move towards skin in anticipation of an injury
Enhancement of memory and sensory information
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Adrenal Medulla
Secretes Catecholamines:
- Epinephrine (adrenaline)
- Norepinephrine (noradrenaline)
- dopamine
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Chronic stress response
Chronic stress can have pathological effects (can cause disease):
Energy availability: type 2 diabetes mellitus
Increased in cardiovascular tone: high blood pressure (problem for variety of diseases including stroke)
Inhibition of reproduction: infertility
Inhibition of growth and repair: psychosocial dwarfism (neglected children and they are small in stature which can be restored by change in environment), slower wound healing
Inhibition of function: immunosuppression (relatively strong suppression of thymus, lymph nodes, spleen - all important immune organs), impaired pathogen resistance
Stimulation of the CNS (too much excitation) : neural degeneration - mild excitotoxicity
Accounts, in part, for widespread stress-related illnesses and psychiatric problems (depression, type 2 diabetes, etc)
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Chronic stressors activates the HPA axis
hypothalamus secretes CRH (corticotropin releasing hormones), particularly neurons in paraventricular nucleus of the hypothalamus
CRH is secreted into the portal vasculature (private blood supply) which leads to the anterior pituitary to the cells called corticotrophs which release ACTH into the general circulation
The ACTH reaches the 2 adrenal cortices (adrenal glands on top of the kidneys) and then stimulates the secretion of cortisol- glucocorticoids (corticosterone in rats) and in some species DHEA (androgen precursor) into blood
81
glucocorticoids
profound effect on elevating blood glucose levels; they cause the breakdown of glycogen in the muscles or liver for increased energy in the bloodstream
Glucocorticoids provide some negative feedback in the HPA axis to the hypothalamus and to the anterior pituitary where they inhibit the production of CRH and ACTH
82
Adrenal Cortex (outer part) got three layers:
(outer) Capsule, Zona glomerulosa, Zona fasciculata, Zona reticularis (then adrenal medulla)
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Zona glomerulosa
secretes aldosterone which is a mineralocorticoid that acts on the kidney; important for absorption of salt and where salt goes, water follows and leads to resorption of water from that kidneys that increases your blood pressure; not necessarily a glucocorticoid involved in the stress response.
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Zona fasciculata
mid zone that secretes cortisol generally in humans and corticosterone in rats, mice, birds, lizards. Cortisol and corticosterone are present; not a either or situation but dominant
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Zona reticularis:
only present in certain species, mice and rats don't have it and do not have much DHEA in the bloodstream. Humans do and they secrete DHEA
86
_____ is a precursor to glucocorticoids
Progesterone
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CBG
~90% of glucocorticoids are bound to CBG (binding protein, each protein can bind to one molecule of glucocorticoid) that helps the glucocorticoid circulate.
When it reaches site of inflammation, it can get cut/cleaved and releases the steroid that CBG is carrying
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Cortisone
a metabolite that is inactive that doesn’ t bind to receptor but enzyme can convert it back to cortisol which is reactivated
89
Dehydrocorticosterone
inactive and can get converted back to corticosterone which is active with enzyme 11-𝛃-HSD1 which is present in the brain depending on brain region
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how is Glucocorticoids important in the orchestration of the entire stress response, particularly chronic stressors?
Liver has lots of glycogen; GC will mobilize the glycogen stores for energy
GC inhibit the steroid production in the gonads and gamete maturation and ovaries
Thymus and bone marrow which are part of the immune system and GC over long term will suppress immunity
91
glucocorticoids in the Hippocampus
Negative feedback to HPA axis; tend to restrain activity in the HPA axis
Many glucocorticoid receptors (GR)
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glucocorticoid receptors (GR) vs. mineralocorticoids receptors (MR)
Glucocorticoids can bind to MR which bind to aldosterone with high affinity
In baseline a lot of the GR are unoccupied and only occupied when there a lot of GC during a stressor
A lot of MR are binded by GC and aldosterone
MR and GR are transcriptional regulators; they will turn and off thousands of genes in the brain and other parts of the body
Pretty much no part of the body that doesn't respond to GC
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Chronic stress can lead to
```
Dendritic atrophy (decrease) of pyramidal cells
Cell loss in the hippocampus
```
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Pyramidal neurons
(large projection neuron that leads out into the hippocampus and is relatively easy to do this kind of quantification) in part of the hippocampus called the CA3 region
95
Golgi stain applied to hippocampus in rodent
Golgi stains fills some small percentages of cells completely
Can map out the dendritic arbors and projections
96
dendritic arbors pf Subordinate animals who were under chronic social stress
Dendritic arbors are smaller (atrophy or even cell death) in the subordinate animals
Dendritic arbors gets larger (growth) in the amygdala
The effect of chronic stress on neuroplasticity depends a lot on what brain area we are talking about
97
_________ is important for spatial learning and memory but also for dampening the HPA axis; disinhibition of HPA axis with atrophy, whereas with amygdala may lead to more vigilance or sensitivity to stressors by dendritic growth
Hippocampus
98
Prolonged high cortisol levels make neurons in the hippocampus vulnerable to
to overstimulation and death by glutamate (excitotoxicity); GC weaken neurons in hippocampus
99
_________ acts as break on cortisol levels; _______damage leads to increased cortisol levels- disinhibition of HPA axis
Hippocampus, Hippocampal
100
Studies of people with depression have found a fairly strong relationship between happy mood and increased activity in the___________
left prefrontal cortex
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Relationship between depression and increased activity in the _________ cortex
right prefrontal cortex
102
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Unipolar Depression (Major Depressive Disorder)
Symptoms:
```
Sad & helpless everyday for weeks, not temporary
Loss of interest, energy or appetite: also referred to as loss of motivation (inersia)
Little or no pleasure from eating or sex; anhedonia: loss of pleasure in things that are normally pleasurable
Feels worthless
Contemplation of suicide
Difficulty in concentrating; attention problems
Impaired sense of smell
Cognitive problems; often persist after successful treatment of the mood problems
Restless agitation and sleep disturbances
Poor memory
Absence of happiness is a more reliable symptom than increase sadness
103
how to test for depressive symptoms in rodents
the forced swim test; latency to float, the less motivation. They look at preference in sucrose. Or operant condition for sugar pellet. They induce depression with chronic stress (unpredictable stressors that animals cannot habituate to)
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Unipolar depression; Genetic component:
60% concordance rate for monozygotic twins
20% concordance for dizygotic twins
Not a single gene defect
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Unipolar depression Medication works for __% of case
60
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Electroconvulsive therapy (ECT)
treatment through an electrically induced seizure
ECT originated with the observation that for people with both epilepsy and schizophrenia, when symptoms of one disorder increase, symptoms of the often decrease
therapists use ECT mostly for patients with severe depression who have not responded to antidepressant drugs and it is effective in most cases
It is applied every other day for 2 weeks
Common side effect of ECT is memory impairment but limiting the shocks to the right hemisphere reduces memory loss; memory loss usually only lasts for a few months
Drawback to ECT is the high risk of relapse; ECT generally acts faster but benefits are less likely to persist
ECT increases the proliferation of new neurons in the hippocampus and increases BDNF levels which antidepressant drugs also increase this increase may or may not be related to therapeutic benefits
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risk factors of depression
Stress (major), long-term inflammation (chronic low grade inflammation, general wide spread), part of immune response, Trouble sleeping
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Depression is correlated with ____- dysregulated in people with depression
HPA-axis
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Stress in rodents very rapidly decrease size of
lymphatic organs such as thymus and spleen which are important for immunity
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People with early onset depression (before the age of 30) have a high probability of
relatives with depression as well as relatives with anxiety disorder, neuroticism, attention deficit disorder, alcohol or weed abuse, OCD, bulimia, migraine, headaches, and irritable bowel syndrome
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for depression research concerns the gene that
controls the serotonin transporters, a protein that regulates the ability of axons to reabsorb serotonin after its release; short form by itself did not lead to depression but it magnified the reaction to stressful events
Short form of the serotonin transporter gene increases emotional reactivity of almost any type, good or bad
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Bipolar Disorder
people with bipolar disorder (manic-depressive disorder) alternate between poles: depression and its opposite side , mania
Bipolar disorder usually has its onset in the teenage years or early 20s
Equally common in men and women
Patients with bipolar disorder frequently have poor sleep quality during manic phases, depressed phases, and even when mood is normal
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mania
Mania is characterized by excitement, laughter, excessive self-confidence, rambling speech, and loss of inhibitions; Brains increase in glucose use during mania and its decrease during depression
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bipolar I disorder
Full fledged Manic episodes
| men are more likely to have severe bipolar I cases
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bipolar II disorder
Mild or hypomanic episodes
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bipolar disorder treatments
Lithium salts; lithium stabilizes mood, preventing relapse into either mania ro depression
The does must be regulated carefully as a low dose is ineffective and a high dose is toxic
Sometimes supplement with antidepressants or antipsychotic drugs which are prescribed for schizophrenia
Antidepressant drugs are risky as they sometimes provoke a switch from depression to mania
Antipsychotic drugs can be helpful but also produce unpleasant side effects
Supplementary strategies include diet and sleep
As with major depression, omega 3 fatty acids, seafood, reduce the risk of bipolar disorder
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what are benzodiazepines and how do they work?
Most common anxiolytic (anti-anxiety) drugs are the benzodiazepines such as diazepam (valium), chlordiazepoxide (librium) and alprazolam (Xanax)
Benzodiazepines bind to the GABAs receptor which includes the site that binds GABA as well as sites that modify the sensitivity of the GABA site
At the centre of the GABA receptor is a chloride channel; when open, it permits chloride ions (Cl-) to cross the membrane into the neuron, hyperpolarizing the cell or at least counteracting any sodium entering the cell through excitatory synapses
GABA synapse is inhibitory. Surrounding the chloride channel are 4 units each containing one or more sites sensitive to GABA; benzodiazepines bind to 3 out of the 4 units
When a benzodiazepines molecule attaches, it neither open nor closed the chloride channel but twists the receptor so that the GABA binds more easily; benzodiazepines thus facilitate the effects of GABA
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Benzodiazepines exert their anti-anxiety effects in the ____,____,___, and several other areas
amygdala, hypothalamus, midbrain
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down sides of benzodiazepines
- possible addiction
- extremely chemically stable and pass through the urine inact, passing through the waste treatment plant intact and accumulate in rivers and lakes where they alter eating and social behavior of resident fish
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Iproniazid
first antidepressant drug- was marketed to treat tuberculosis but it relieved depression
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Antidepressants fall into several categories:
tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors and atypical antidepressants
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Tricyclics
(e.g. imipramine aka Tofranil) block the transporter proteins that reabsorb serotonin dopamine and norepinephrine into the presynaptic neuron after their release
Triculic drug locks the transporter into the initial position
The result is to prolong the presence of the neurotransmitters in the synaptic cleft where they continue stimulating the postsynaptic cell
Tricyclics block histamine produces drowsiness
Blocking acetylcholine leads to dry mouth and difficulty urinating
Blocking sodium channels causes heart irregularities among other problems
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Selective serotonin reuptake inhibitors (SSRIs)
similar to tricyclics but specific to neurotransmitter serotonin
They attach to the center of the serotonin transporter protein and lock it into shape that prevents serotonin from binding to tit
Milder side effects than tricyclics; effectiveness is about the same
Common SSRIs include fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), and paroxetine (Paxil or Seroxat)
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Serotonin norepinephrine reuptake inhibitors (SNRIs)
duloxetine (Cymbalta) and venlafaxine (Effexor), block reuptake of both serotonin and norepinephrine
SNRIs improve certain aspects of memory
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Monoamine oxidase inhibitors (MAOIs)
Monoamine oxidase inhibitors (MAOIs) (e.g. phenelzine, trade name Nardil) block the enzyme monoamine oxidase (MAO) a presynaptic enzyme metabolizes catecholamines and serotonin into inactive forms
MAOIs block this enzyme, the presynaptic terminal has more of its transmitter available for release
The MAOIs were the earliest antidepressants but no longer the first choice
People taking MAOIs must avoid foods containing tyramine including cheese raisins, and many others because a combination of tyramine and MAOIs increases blood pressure
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bupropion (Wellbutrin)
Atypical antidepressants-inhibits reuptake of dopamine and to some extent norepinephrine but not serotonin
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Ketamine
antagonizes NMDA-type glutamate receptors but also increases formation of new synapses, produces rapid antidepressant effects in patients who don’t respond to other medications; produces hallucinations and delusions and benefits are not long lasting
Ketamine itself would not be suitable antidepressant but preliminary results suggest that one of ketamine’s metabolites might be potential candidate
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St. John's wort, an herb
antidepressant because it is a nutritional supplement U.S. Food and Drug Administration does not regulate it and its purity varies from bottle to bottle
It's cheaper and available without prescription; people can easily take inappropriate amounts
Its effectiveness appears to be comparable to standard antidepressants
Increases effectiveness of a liver enzyme that breaks down plant toxins and breaks down most medicines
Decreases effectiveness of other drugs someone may be taking
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tryptophan
the precursor to serotonin
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brain-derived neurotrophic factor (BDNF) and levels of it in depressed people
Most people with depression have lower than average levels of a neurotrophin called brain-derived neurotrophic factor (BDNF) which is important for synaptic plasticity learning and proliferation of new neurons in the hippocampus
Antidepressant drugs increase BDNF levels over the course of weeks (consistent with the time course for antidepressants to take effect)
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Results of low BDNF most people with depression have
a smaller than average hippocampus, impaired learning, and reduced production of new hippocampal neurons
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important features of antidepressant effects
Proliferation of new neurons in the hippocampus, associated with new learning is important for antidepressant effects; Importance of new learning may explain why antidepressants don't elevate the mood of people who are not depressed; those who are not burdened with discouraging thoughts that they need to unlearn; drugs also exert essential effects on mature hippocampal neurons
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Cognitive behavioral therapy
and other forms of psychotherapy are often helpful
Antidepressant drugs and psychotherapy are about equally effective for treating all levels of depression from mild to severe
Brain scans show that antidepressants and psychotherapy increase metabolism in the brain in the same areas
Psychotherapy has an advantage because its effects are more likely to last
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Omega 3 fatty acids are important for__________ and vitamin B6,9 and 12; however research is not entirely conclusive
neuron membranes
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Altered sleep patterns
almost everyone with depression has sleep problems
Sleep problems generally precedes the mood changes
someone with depression resembles the sleep of healthy people who have traveled a couple of time zones west; they fall asleep when the clock says to do so but they enter REM sleep sooner than normal and awaken early
Depressed people can stay up all night and feel substantially improved but benefits from sleep deprivation is rapid and brief as depression usually returns after the next night's sleep
Sleep earlier and get a normal amount of sleep with normal timing or REM sleep, usually relieves depression quickly and benefits last for a week or more
But circadian rhythm shifts again but phase advancing the sleep schedule has become a popular therapy
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Deep brain stimulation
a physician implants a battery powered device into the brain to deliver periodic stimulation to certain brain areas (that show increase due to antidepressant drugs)
Patients who fail to respond to all other treatments show gradual improvements over months about half get fully back to normal as long as the stimulation continues
A possible refinement of this procedure is to use optogenetic stimulation which can control individual connections rather than all the axons going around one area to another
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Dexamethasone (DEX)
DEX is an artificial GC which binds to the GR with high affinity and provides negative feedback
DEX can be injected or taken orally
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DEX levels healthy person before and after administration
Normal controls:
Day one is pre DEX day NORMAL : cortisol levels rise early in the morning before waking up and go down, rise again around noon and go down, and rise again before dinner and then go down again
Day 2 post DEX : cortisol levels are very low and stay low throughout the day- dexamethasone suppression
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DEX levels depressed patient before and after administration
The cortisol pattern is irregular compared to normal
With DEX: there is still a rise in cortisol at some points in the day
Person is in hospital being measured
This study suggests and impairment in the negative feedback; something dysregulated in the HPA-axis
Correlational study
Bio marker- blood test with IV regularly to obtain clear profile to identify difference between depressed and normal people
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Immune system
Defends the body against pathogens and infectious agents such as viruses, bacteria, fungi… and cancer, damaged cells, etc.
A fundamental aspect of this involves differentiating “self” from “non-self”
This is accomplished primarily by white blood cells (leukocytes)
Monocytes, lymphocytes, etc.
The nervous system and immune system interact in both directions
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Non-specific (innate) immunity
Rapid, first in line of defense, monocytes, and macrophages
Destroys anything “non-self”
But in the process, can also damage “self” own cells
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Specific (adaptive) immunity: COVID vaccine
Takes time to develop but more specific and less likely damage of own cells
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Cell-mediated immunity
Involves T cells (type of lymphocyte)
| Kills specific pathogens upon re-exposure to a pathogen
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Antibody-mediated (humoral) immunity
B cell growth factor, cytokine, that stimulates division of B cells which then release antibodies that tag virus for destruction
Antibodies are attached to B cells and released into circulation to encounter antigen and bind to it
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Lymphocytes: B cells
Lymphocytes originate/mature in the bone marrow
A lot of different blood cells originate from bone marrow including red blood cells
B cells produce these antibodies (proteins present in nervous system)
Those that mature in the bone marrow are termed B cells and participate in antibody-mediate (humoral) immunity
Antibodies: Y-shaped proteins that attach to particular kinds of antigens- each arm can bind to one arm of antibody
Antigens: proteins on cells, viruses, fungi etc
Antibody-tagged cells are destroyed by macrophages (other immune cells)
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Lymphocytes: T cells
Some lymphocytes migrate from the bone marrow to the thymus
Lymphocytes that mature in the thymus are termed T cells and participate in cell-mediated immunity
Attack pathogens directly (cytotoxic T cells- have marker on it called CB8-CB8 positive cells) and also help other T cells or B cells to multiply or proliferate (helper T cells- have a marker called CB4- called CB4 positive cells)
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Cytokines
Hormone of immune system that tells the brain that there may be an infection
During an infection leukocytes and other cells produce small proteins called cytokines
Immune cells that multiply and combat infection and inform brain
Cytokines stimulate the release of prostaglandins
Produce fever (caused by cytokines acting in the brain to regulate body temperature which helps kills pathogens), sleepiness, withdrawal from social behavior, loss of appetite -> conserves energy
Too much cytokine (over-response of immune system e.g. COVID, can be just as bad as too little response)
In some cases, the cytokine can cross BBB and act on the hypothalamus where BBB is leaky
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Cell mediated Immunity: circle with cytokine is the excitotoxic T cells and T with circles is the cytotoxic T cells proliferating
A macrophage might encounter an infectious agent (e.g.COVID) and then secrete interleukin-1 which is a cytokine that then activates T helper cells which then would secrete another cytokine, interleukin-2, which cause other T cells to proliferate and divide which attacks the infectious agent
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After vaccination, Antibody-mediated immunity
we get memory; memory T cells and memory B cells which prepare you for if you were to see that antigen again
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Immune system secretes various ______ that reach the brain and affect behavior and nervous system function even affect different hormone levels
cytokines
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Lots of __ on T cells and B cells, positioned to respond to __ quite strongly
GR, GC
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______directly innervates (supply other organs with nerves) the spleen, thymus, lymph nodes, etc. mechanism of direct modulation of_________ by the ____________; bidirectional relationship
Nervous system, immune system, nervous system
