GERO 508 Spring 2021Week 2The Mind & Body Connecti

GERO 508 Spring 2021
Week 2
The Mind & Body Connection
Timothy Lu Office Hours: By Appointment Email:
[email protected]
Dr Paul Nash CPsychol, AFBPsS, FHEA
Office: GERO 231E
Office Hours: Thurs 09.00-12.00
(OR AGREED APPOINTMENT)
Email: [email protected]
Gillian Fennell
Questions about assessments?
2

The session in brief
Biological – What is stress?
Biological consequences of stress
Biological models of stress
Measuring biological stress
What does stress look like?
The meaning of sex
Psychological approaches to stress
Environmental approaches to stress
Specific models of stress
Bio-Psycho-Social models of stress
Measuring psychological components of stress
3

What forms can stress take?
4
Stress – The overview
Actual Stress
- See a predator / See a car coming towards you
5
Perceived Stress
- In a situation where something may or may not happen
Which do you think happens with humans? Why?
Humans exhibit the anticipatory stress response, well done us!!
Turn on stress response for psychological reasons
- memory, emotions, thoughts

NOT what stress was designed for which leads to potential for
chronic stress
Essentially the aim of the stress response is to return us to the
homeostatic equilibrium we are in.
Acute or Chronic?
6
The meaning of sex
7
Fight or Flight
Tend and Befriend
Evolutionary
Protection of self and offspring
Nurturing offspring under stressful situation
Protect from harm (tend)
Create / join social groups to maximize resource and
protection (befriend)
Evolutionary
Protection of self
Fight a stressor

Escape a stressor
Short lived
Few mins – Alive or dead
Most research based on males until the tend / befriend
hypothesis produced. Mainly due to different cyclical variation
in hormones and endocrine responses making research with
women less predictable.
Not the whole story and we have biological and psychological
differences later in the course!
Stress – The psychological approach
8
Stress as a response
The ways in which we respond to a stressor
Storm and stress approach
Coping & resilience
Effects of prolonged stress
Stress as a stimulus
Views stress as a significant life event or change that demands
response, adjustment, or adaptation
Sees change as inherently stressful
Stress is dealt with uniformly across populations
Illness outcome thresholds are uniform
Stress as a transaction
Stress is a product of the human – environment transaction
Hardiness, resilience, locus of control and self-efficacy are
important constructs
Duration of transaction (Episodic, Acute, Chronic)

Environmental stressors
9
Suboptimal environmental conditions pose demands that may
exceed an individuals ability to cope
The imbalance between environmental demands and response
capabilities is called…..?
…Stress
Environmental stressors include:
Chronic
Noise when living by a freeway
Acute
Noise when in a tunnel
Which is more impactful?
Chronic is more impactful and more likely as individuals have
less ability to escape from them: Worked example, Airports

Some environmental stressors affecting YOU in LA
10
Noise
Intensity (decibel); Frequency (pitch); Periodicity (continuous
or not); Duration (acute or not)
Noise is more than sound. Characteristics affecting this are:
Intensity
Unpredictability
Uncontrollability
But what can chronic noise actually impact?
Psychological stress (Ising and Kruppa, 2007)
Increased noradrenaline levels and BP in children (Evans et al.,
1998)
Increased BP in high noise work environments (Tomei et al.,
2010) Reduced reading ability in children (Bronzaft, 1981)
Attention and task discrimination (Evans & Hygge, 2007)
Memory (Cohen et al., 1986)
When there was control, the effects were mitigated

Some environmental stressors affecting YOU in LA
Poor neighborhood quality
Quality of municipal & retail services; recreational opportunity;
traffic; transportation links; noise; crowding; community
transience; healthcare; education opportunity
Similar to the others, there is a lifespan effect
But what can a poor environment actually impact?
Greater psychological distress for children in poorer
environments (Gifford & Lacombe, 2006) Similar trends both
longitudinally (Dalgard & Tambs, 1997) and cross-sectionally
(Gary et al., 2007)
Increased physiological stress in adults and children (Hill et al.,
2005; McGrath et al., 2006) Effects of community are
experienced irrespective of household SES (Evans, 2004)
What can be done to improve poorer environments to reduce
stress?
12

General Adaptation Syndrome (GAS)
The Alarm Phase
The alarm reaction stage refers to the initial symptoms the
body experiences when under stress.
The “fight-or-flight” response – the physiological response to
stress. This natural reaction prepares you to either flee or
protect yourself in dangerous situations. Heart rate increases,
Adrenal gland releases cortisol (a stress hormone), and you
receive a boost of adrenaline, which increases energy.
Selye, 1936
13
General Adaption Syndrome (GAS)
The Resistance Stage
After the initial shock of a stressful event and having a fight-or-
flight response, the body begins to repair itself. It releases a
lower amount of cortisol, and your heart rate and blood
pressure begin to normalize. Although your body enters this
recovery phase, it remains on high alert for a while. If you
overcome stress and the situation is no longer an issue, your
body continues to repair itself until your hormone levels, heart
rate, and blood pressure reach a pre-stress state.
Some stressful situations continue for extended periods of time.
If you don’t resolve the stress and your body remains on high
alert, it eventually adapts and learns how to live with a higher
stress level. In this stage, the body goes through changes that

you’re unaware of in an attempt to cope with stress.
Your body continues to secrete the stress hormone and your
blood pressure remains elevated. You may think you’re
managing stress well, but your body’s physical response tells a
different story. If the resistance stage continues for too long of
a period without pauses to offset the effects of stress, this can
lead to the exhaustion stage.
Signs of the resistance stage include: irritability
frustration
poor concentration
14
General Adaption Syndrome (GAS)
The Exhaustion Stage
This stage is the result of prolonged or chronic stress.
Struggling with stress for long periods can drain your physical,
emotional, and mental resources to the point where your body
no longer has strength to fight stress. You may give up or feel
your situation is hopeless. Signs of exhaustion include:
fatigue
burnout
depression
anxiety
decreased stress tolerance
The physical effects of this stage also weaken your immune
system and put you at risk for stress-related

illnesses.
15
Diathesis Stress model
Diathesis
Predisposition (genetic, psych, bio, environmental, situational,
personality type)
Stress
Events resulting in the disruption of the psychological
equilibrium
Nature v Nurture
Disorders linked with this model:
Alcoholism; Schizophrenia; Anxiety; Depression
What do you think are the protective factors?
Social support; Network typology; Environment; Self-esteem
Expanded into the ‘Differential Susceptibility Hypothesis’
(Belsky et al., 2007) – Look it up!!
16
A stage model of stress

‘Events appraised as stressful are viewed as triggering affective
states that in turn engender behavioral and biological responses
having possible downstream implications for disease’
(Cohen, Gianaros & Manuck, 2016)
Combines:
Epidemiology
Defining which circumstances and experiences are deemed
stressful on the basis of consensual agreement that they
constitute threats to social or physical well-being
Psychology
Individuals’ perceptions of the stress presented by life events
on the basis of their appraisals of the threats posed and the
availability of effective coping resources
Biology
Brain-based perturbations of physiological systems that are
otherwise essential for normal homeostatic regulation and
metabolic control
17
A stage model of stress – more detail
Stressors trigger a brain-based perceptual appraisal which in
turn triggers an affective response (stress / anxiety)
Affective responses change the way both HPA( hypothalamic–
pituitary–adrenal system) & SAM (sympatho-adrenal-

medullary mediators) function.
Affective responses also impact emotional responses and
behavioural outcomes / health risk behaviours like drinking and
smoking
Appraisals of stress and their affective sequelae can influence
interpretations of physiological sensations, such as defining
sensations as symptoms and symptom clusters as diseases that
in turn influence health-care seeking, and adherence to medical
regimens
18
A stage model of stress – Keep in mind
Common criticisms include:
Too Sequential
However, although the model is sequential, emphasizing the
proximal predictive nature of each stage, this is demonstrative
of the integration of the Biological, Environmental and
Psychological constructs. Further, the authors repost that other
mechanisms can be at play rendering some stages obsolete in
different situations
Unidirectional Model
Feedback loops (e.g. depression in final stage can feed into
negative appraisals) mean that the model has Omni-
directionality
19

Next time…
20
Week 3
02/04/2021Stress and genetics
(Lu/Nash)SEE BBWeek 2 Discussion
Week 2
Biological Aspects of Stress
Timothy Lu
Office: Virtual
Office Hours: By Appointment
Office: GERO 231E
Office Hours: Weds 09.00-12.00
Gillian Fennell

Biological Aspects of Stress
22
What are the main biological components involved in stress?
How does the brain react?
How the brain triggers the body to respond
How does acute stress differ from chronic stress?
What diseases may manifest from chronic stress? (which we’ll
talk more about in future lectures)
First, a disclaimer:
23
The stress response itself is not harmful
Stress response (in general) is adaptive
It allows us to respond to threats accordingly!
Why then, does stress become an issue with us humans?
What is stress?
24
Stress is the body’s method of reacting to a condition perceived
as dangerous and/or harmful, including threats, challenges and
physical or psychological barriers
The body reacts to stress via the fight-or-flight response: a
psychophysiological reaction in response to a perceived harmful
event, attack or threat to survival
This response is regulated by the autonomic nervous system, a
division of the peripheral nervous system which acts largely

unconsciously to regulate bodily functions
The agents of stress are stressors, which may be internal or
external. Key to stress is some amount of (perceived) loss of
control over physical or psychological safety.
Physical triggers
25
Animate triggers from other species: predators, infectious
agents
Inanimate triggers: floods, earthquakes, fires, avalanches,
storms, hurricanes, riptides, other natural calamities
Humans and many other species can also experience stress
induced by interactions with members of their own communities
Psychological/social triggers
26
Concerns about one’s place in the universe
Providing for the necessities of life
Security (physical, social, psychological)
Social achievement
Social hierarchy advancement
Relationship with peers
Concerns about the environment
Conditions which threaten homeostasis

Crisis & unrest
Many stress triggers observed in animal societies have parallels
in human society
Neurons – Components of the Brain
27
Dendrites receive signals.
As neuron gets activated by incoming signals, the “summed
signals” from many inputs goes to cell body.
Cell body integrates and makes decision on the importance of
the signal (s).
If signals are important enough the cell body/hillock discharges
and the receiving cell sends its own signal out the axon to next
neuron in the sequence.
In the cell body we have the nucleus. Activity on the neuron
will influence the nucleus to make proteins based on the needs
of the nerve cells (using DNA expression and RNA recipes).
Neuronal Communication
28
The connection between two neurons is a space known as a
synapse
Generally, this connection is chemical (although sometimes it is
electrical)
Important this signal is uninterrupted

We have excitatory/inhibitory signals
What might happen if this connection is interrupted?
What is the importance of inhibitory signals?
28
Important Brain Anatomy to Know
29
Frontal Lobe – executive functions
Parietal Lobe – processing of somatosensory information
Occipital Lobe – processing of visual information
Temporal Lobe – processing of auditory information
The frontal lobe is going to be the primary decision maker –
this lobe is responsible for your entire existence (from your
speech decisions, motor movements, and other life choices
you’ve made) and as such is a critical part of the stress response
in terms of ASSESSING stressors or even being a part of them!
Frontal Brain Importance
30
Impaired function: Clinical depression, ADHD, anxiety,
overactive stress response, addiction, etc;

Important Brain Anatomy for Stress Modulation
31
Amygdala – primary stress response
Basal nuclei – movement
Hippocampus – memories
Hypothalamus – bodily integration
Thalamus – sensory information gateway
Pituitary glands – hormonal release
The amygdala is the primary structure involved in the stress
response. It triggers the activation of the hypothalamus to
communicate with the pituitary gland and send out hormones
that are important to the stress response. The hippocampus
stores memories that can relate to the stress response and
trigger it (such as in PTSD)
Hormones and their function
32
A hormone is any member of a class of signaling molecules
produced by endocrine glands and transported by the circulatory
system to target organs, where they modulate physiology and
behavior

A corticosteroid is a type of hormone secreted by the adrenal
glands
Adrenaline (epinephrine) increases blood flow and blood sugar
levels
An important class of corticosteroids are the glucocorticoids,
which regulate glucose (blood sugar) and modulate the stress
response, immunity, inflammation and behavior
Cortisol increases blood glucose and suppresses immunity and
inflammation
The adrenal glands – Stress hormone releaser
33
The adrenal glands are located above the kidneys and secrete
two very important hormones: adrenaline and cortisol
An adrenal gland consists of two distinct anatomic divisions:
the cortex and the medulla
The cortex produces steroid hormones like glucocorticoids
(cortisol is only one example)
The medulla produces adrenaline
https://www.youtube.com/watch?v=06jbq3bxKE0
Memory and Emotions
34
Amygdala closely related to hippocampus – strong relation to

memory centers
This means stressful/fear-inducing events become greatly
attached to our memory
Alzheimer’s is an age-related disease that leads to the
degradation of memory centers
Chronic stress can induce damage to these memory areas
Emotional events in general tend to be deeply ingrained in our
memory!
What do you think could occur with stress induced memory
loss?
Why do you think emotions are so important to our memory?
34
What can the brain do to impact the body?
35
Brain to body interaction for stress
36
Sympathetic Nervous system (Fast)
Slow response (hormonal):
1. Second wave of energy
2. Shut off unnecessary physiology

3. Shut off stress response via negative feedback
Brain to body interaction for stress
37
Under conditions when a subject feels alert, safe and interested,
phasic release of catecholamines (adrenaline and dopamine)
strengthens the higher cognitive functioning of the PFC, thus
allowing top-down regulation of thought, action and emotion. In
primates, the PFC is topographically organized, with the dorsal
and lateral surfaces mediating attention, thought and action
while the ventral and medial aspects mediate emotion (tells the
amygdala to SHUT UP – it inhibits the amygdala).
During stress exposure, high levels of catecholamines
(adrenaline) take the PFC 'off-line' while strengthening the
functions of more primitive circuits—for example, the
conditioned emotional responses of the amygdala and the
habitual actions of the basal ganglia. The amygdala activates
brainstem stress systems, which in turn activate the sympathetic
nervous system.
Stress weakens prefrontal networks: molecular insults to higher
cognition
http://www.nature.com/neuro/journal/v18/n10/full/nn.4087.html
?WT.ec_id=NEURO-
201510&spMailingID=49632583&spUserID=ODkwMTM2NjI1O
AS2&spJobID=763426042&spReportId=NzYzNDI2MDQyS0

Focus on the SYMPATHETIC (stress) response
38
How does this all work together?
39
HPA Axis and the feedback loop
The hypothalamic-pituitary-adrenal (HPA) axis is the loop of
our stress response.
The hypothalamus sends corticotropin releasing hormone (CRH)
to the pituitary gland. The pituitary releases adrenocorticotropic
hormone (ACTH) to the kidneys, specifically the adrenal glands
on top of the kidneys. The adrenal glands then release cortisol
(shown as corticosterone for rats) which affects the body. This
cortisol creates a negative feedback loop which shuts itself off.
What we will learn is that this is not always the case in chronic
stress. We will talk more about the effects of cortisol on the
body.
39

Stress, socioeconomic status and ethnicity
40
Low social rank is associated with more stress across human
societies
Studies indicate that this is the case even when accounting for
factors like financial security, access to healthcare, education
and other factors
Because more stress is associated with higher inflammation, this
suggests that individuals who are members of disadvantaged
social groups can be at higher risk for cardiovascular disease,
neurodegenerative disorders, anxiety and depression
Members of social groups who are at higher risk for
discrimination can be more likely to experience prolonged
stress and its consequences
These considerations are not yet properly understood
scientifically but there are substantial efforts now underway to
clarify and alleviate socioeconomic and ethnic disparities in
stress-related morbidity and mortality
https://www.youtube.com/watch?v=bEcdGK4DQSg
Biological Measures of Stress
41
Measuring stress biologically comes in many forms, what do
each of these tell us?
We can look at stress hormones: cortisol
We can look at other biomarkers that come from the stress
response:
blood urates – byproduct of protein degradation (neuronal)
Lysozymes – antibacterial enzyme (decreases)
CRP – elevated marker of inflammation/stress
miRNAs – influence biological systems
heat shock proteins – induced by short-term stress (anti-

inflammatory)
Measured in the blood and saliva
https://www.frontiersin.org/articles/10.3389/fmolb.2019.00091/
full
41
Stress effects upon neural cells and brain structure
42
The hippocampus is a brain structure which plays a central role
in memory formation
In stressed mice, neurons have fewer dendrites and the
hippocampus is smaller
Chronic stress changes brain circuits such that we slowly lose
the ability to remember things
This is the hallmark of Alzheimer’s disease
Stress effects upon brain circuitry
43
Stress/glucocorticoid excess have been linked to
Decreases in the connectivity of the hippocampus and frontal
cortex

Increases in the connectivity of the amygdala, a structure
involved in the processing of emotions and affect
Brain networks can be very susceptible to hormonal imbalances,
such that abnormal levels of inter-connectivity between regions
can be linked to anxiety and depression
Connections between the limbic system and prefrontal cortex
are often affected substantially
Stress effects upon neurotransmission
44
Behavior and affect are intimately linked to the chemistry of the
brain
When a neurotransmitter called dopamine is released at the
synapse, it binds to receptors signaling pleasure in anticipation
of a reward
Dopamine is released not when the reward arrives, but when it
is anticipated: “Success is a journey, not a destination”
Positron emission tomography (PET) is an imaging technique
which can be used to investigate dopamine receptor binding
PET can also be used to investigate the concentration of glucose
in the brain and to study how the metabolic needs of neurons
are correlated with stress
https://www.youtube.com/watch?v=NxHNxmJv2bQ
https://www.youtube.com/watch?v=GHLBcCv4rqk

Impact of stress on the brain and body
45
Increased stress leads to decreased response to dopamine
This decrease in dopamine leads to a decreased feeling of
reward
Increased stress also affects metabolism which may lead to
obesity
During the semester we will explore the impact of stress on
different bodily systems
More on exercise in a later lecture
45
Stress and the heart
46
https://www.youtube.com/watch?v=1djrTfY74yg
Stress and atherosclerosis
47
Because stress and the resulting flood of hormones increase
blood pressure, the cardiovascular system is subjected to
mechanical stress associated with higher blood pressure and
pulse rate

High blood pressure damages artery walls
Damaged artery walls become repositories for plaque
Plaque restricts blood flow and increases the risk of heart attack
Atherosclerosis is a condition where the interior of arteries
becomes narrower because of plaque
https://www.youtube.com/watch?v=1rv7GbUPXC4
Other Diseases Caused by Stress
48
Stress can greatly impact the body and lead to various diseases
such as…
Diabetes
Atherosclerosis
Cardiovascular issues
Weakened immune response
Obesity
General Adaptation Syndrome (GAS) - RECAP
Selye, 1936
49

Diathesis Stress model – Recap
Diathesis
personality type)
Stress
equilibrium
Nature v Nurture
Disorders linked with this model:
Alcoholism; Schizophrenia; Anxiety; Depression
What do you think are the protective factors?
Social support; Network typology; Environment; Self-esteem
Expanded into the ‘Differential Susceptibility Hypothesis’
(Belsky et al., 2007) – Look it up!!
50
A stage model of stress – Recap
51
‘Events appraised as stressful are viewed as triggering affective
states that in turn engender behavioral and biological responses
having possible downstream implications for disease’
(Cohen, Gianaros & Manuck, 2016)
Combines:

Epidemiology
Defining which circumstances and experiences are deemed
stressful on the basis of consensual agreement that they
constitute threats to social or physical well-being
Psychology
Individuals’ perceptions of the stress presented by life events
on the basis of their appraisals of the threats posed and the
availability of effective coping resources
Biology
Brain-based perturbations of physiological systems that are
otherwise essential for normal homeostatic regulation and
metabolic control
Bio-Psycho-Social Model
52
Back to your roots
Fight or flight today – Same as evolution indented?
Some bosses may be predators but essentially, no. But we have
similar physiological if not behavioural responses
Something to consider:
What do you think the impact of social hierarchy is?
Primates, as with humans, who are higher up the social
hierarchy have fewer stress hormones

Less stress
Less sickness
53
Take a lifecourse perspective
- People who are susceptible to high stress often have a
background being bullied or abused
Back to the monkeys:
Primates have 1 alpha per pack but impossible to have a global
alpha so much postulating and social domineering esp in
workplaces
Removing the alphas reduces status play, harassment and
increased socialization.
Can this be done with humans?
Reduce fiscal inequality; reduce vertical management hierarchy
and increase autonomy in decision making; increase individual
control

54
Which is better, the whole pizza of just the base?
Easier to allow a dominator hierarchy to form (pizza base)
which controls and suppresses other aspects of personality and
responses
‘Core Transformation’ suggests embracing all aspects of self,
integrating not repressing
Similar principles to adjusting primate behaviour
Why do we ‘pizza base’?
Ease / laziness; Social norms; Dislike of aspects of personality;
Self-presentational bias; Maintaining social standing
Just how well do you fair?
55
Holmes Social Readjustment Rating Scale
Take a pen and paper
Write down the values for each event that is relevant to you
(within last 12 months)

Total your score
Reflect
Life EventPoint ValueDeath of spouse100Divorce73Marital
separation65Jail term63Death of close family
member63Personal injury or illness53Marriage50
56
Fired from job47Marital reconciliation45Retirement45Change
in health of family member44Pregnancy40Sex
difficulties39Gain of new family member39Business
readjustment39
57

Change in financial state38Death of a close friend37Change to
different line of work36Change in number of arguments with
spouse35Mortgage over $10,00031Foreclosure of mortgage or
loan30Change in responsibilities at work29Son or daughter
leaving home29Trouble with in-laws29
58
Nearly there…
59
Outstanding personal achievement28Spouse begins or stops
work26Begin or end school26Change in living
conditions25Revision of personal habits24Trouble with
boss23Change in work hours or conditions20Change in
residence20Change in schools20
Change in recreation19Change in church activities19Change in
social activities18Mortgage or loan less than $10,00017Change
in sleeping habits16Change in number of family get-
togethers15Change in eating
habits15Vacation13Christmas12Minor Violations of the law 11

60
Totting it up
61
150 points and below: It implies you are less likely to
experience a health breakdown.
151-300 points: It implies you have a 50% chance of a major
health-breakdown in the next two years.
301 points and above: It implies you have an 80% chance of a
major health breakdown in the next two years.
Is it that straight forward?
62
Issues with the HSRR:

Assumes that all events have same stress value for everyone
Assumes that the anchoring is accurate
Not age-rated (all stresses have the same values at all points in
the life span)
Some stress is positive
Thoughts?!?
Additional Reading
63
Social vs environmental stress
https://www.sciencedirect.com/science/article/pii/S0924977X12
001459
Animal models of social stress
https://www.tandfonline.com/doi/full/10.1080/10253890.2018.1
462327?scrol l=top&needAccess=true
Social stress models
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901160/

Week 3
[email protected]
Office: GERO 231E
Gillian Fennell
65
Nature v nurture?
Influences factors for genetic predisposition
Influence of personality types
Coping mechanisms
Appraisal models
Integrated approach to genetic predisposition

Nature vs Nurture?
66
https://www.khanacademy.org/test-
prep/mcat/behavior/behavior-and- genetics/v/gene-environment-
interaction
Revisiting the Diathesis Stress model
67
Diathesis
personality type)
Stress
equilibrium
Nature via Nurture
Factors that affect the genetic predisposition
20

What are the factors that can influence genetic predisposition?
Culture: Food Tradition Expectation Religion Others?
Intrapersonal / Interpersonal:
Internal concerns
(health, money, future etc) Communication with others
Social Network: Friends
Family
Civic engagement Confidant?
Gender:
Roles
Expectation / opportunity
Modern Life: Work hours Tech reliance
24 / 7 immersion Unhealthy lifestyle Drink / substances
Factors that affect the genetic predisposition
21
S.E.S.:
Income Education
Access to services Type of work
Leisure time / activity
Built Environment: Neighborhood type Housing stock
Green spaces / urban planning Urban vs rural
Transportation Visible incivilities Crime

Personality types: State / Trait Attitude
Locus of Control
Type A or Type B
A
High-achievers, great at multi-tasking unrelated duties and
jobs, usually perform beyond par.
Constantly in a race to achieve higher goals. When goals are
attained, they set much loftier aspirations.
Difficult to accept failure. It is never one of their realities. For
them, others fail, they don’t.
Time is an opponent that they have to beat every day. They will
work to exhaustion.
Severe sense of urgency makes them edgy. Relaxation is
difficult
Highly competitive. If there is no obvious competition, they
create one.
Highly self-driven. Their stress levels are generally high.
22
Friedman & Rosenman (1976)
B
Know their abilities and work steadily for their goals. They
enjoy their achievements.
Not too stressed out to excel. They can be disappointed when
they fall short of their goals, but they are not devastated. They
are more accepting of failures.
Enjoy games and competitions, not for the sole objective of
winning but for the love of the game.
Reflective and innovative. They allow themselves to explore

and fail, if necessary.
Sometimes they are too relaxed and laid-back that they lack the
drive to reach the uppermost of their careers.
Even-tempered.
They typically live less stressful lives.
It takes 2…… or 3
71
People with Type B personality tend to be more tolerant of
others, are more relaxed than Type A individuals, more
reflective, experience lower levels of anxiety and display a
higher level of imagination and creativity.
The Type C personality has difficulty expressing emotion and
tends to suppress emotions, particularly negative ones such as
anger. This means such individual also display 'pathological
niceness,' conflict avoidance, high social desirability, over
compliance and patience.
Coping Mechnisms: Problem focussed coping
72
Basic Principles:
undoing repairing preventing

Examples:
get information
make changes (do what is needed: ask for the raise)
escape from the situation (eg a bad relationship)
make a plan of action and follow it
Coping Mechanisms: Emotion focussed coping
25
Basic Principles:
Changing the meaning of the transaction Regulating its
expression
The coping actions are focused on dealing with the emotions not
the situation.
Examples:
Wishful thinking: I wish the situation would just go away or
somehow be over with.
Distancing: I try to forget the whole thing.
Emphasizing the positive: I try to look at the bright side of
things.
Self-blame: I realize I brought the problem on myself
Tension-reduction: I try to make myself feel better by
eating, drinking, smoking, or using drugs or medications.
self-isolation: I keep others from knowing how bad things are
seeking social support: I talk to someone to find out more about
the situation.
Prayer, reading Scripture

Comparing the two
74
One or the other?
75
Do you think that these coping strategies are situation driven?
Individual driven? Contextual? Or enduring personality traits?
In difficult situations, there is a mix of problem focused efforts
to do something to change the situation for the better and
emotion focused efforts to sustain morale and feel better about
the situation.
Examples: disability, pain management
Applied to older adults
76
Costa & McCrae
older people have more negative stresses (health problems,

death, etc) but cope as well as younger ones do
no age differences in coping
Young (age 35-45): finances, work, taking care of household,
dealing with family and friends More sense of control, equal
balance of problem and emotion focused coping.
Old (65-74): health, difficulties with ADL’s.
Greater reliance on emotion focused coping.
HOWEVER….. Is it specifically age related….
Is it just about ageing?
77
Are these specifically developmental or related to life situation?
People learn to reorganize life to cope with disability,
regardless of age
Aging may teach us the lessons of how to cope--despite more
limited resources, it may be the experiences of loss over a
lifetime that gives us the best resources to handle problems.
Key points…
78

Next time…
Week 4
02/11/2021Clinical depression and stress
responses (Lu/Nash)SEE BBWeek 3 Discussion
31
Week 3
Genetic Aspects of Stress
Timothy Lu
Office: Virtual
Office Hours: By Appointment
Office: GERO 231E
Office Hours: Weds 09.00-12.00
Gillian Fennell

Genetic Overview
81
DNA is the fundamental building block of our cells
Everything that we have comes from somewhere within our
DNA
DNA is not constant! It can change and mutate over our lives
naturally as well as stimulated to change
These changes can be carried down across generation
(epigenetics)
Stress impacts our DNA
DNA Overview
82
DNA is a molecule consisting of a double helix carrying genetic
instructions used in the growth, development, functioning and
reproduction of all life forms
Chromosomes are DNA molecules containing an organism’s
genetic code
Nucleosomes are formed by DNA winding around core particles
and are connected by linker DNA
Nucleosomes fold into looped chromatin coils
Humans have 46 chromosomes; two of them determine and
contain information pertaining to sex

Genetic Variation
83
Genes are DNA sequences which code for functional molecules
called proteins
Proteins are complex molecules which have specific functions
within the cell
Genetic variation is the variability of biological systems
(individuals and populations)
Genetic variation is partly made possible by alleles, which are
variant forms of a certain gene
Example: the APOE gene encodes the APOE protein, which has
a role in how fats are processed and has three major alleles (ε2,
ε3, ε4)
We each have two APOE alleles, one from each parent
The ε4 allele increases the risk for Alzheimer’s disease; the ε2
allele is protective; ε3 is neutral
DNA to proteins
84
Transcription
Genes are copied from DNA to RNA in the nucleus of the cell
Translation
RNA is transported out of the nucleus to the cytoplasm
The ribosome (a cell organelle) assembles protein chains based
on instructions contained in RNA
Protein synthesis (production)
Protein chains break off from the ribosome and then undergo

changes in shape and structure to form proteins
DNA Replication
85
DNA is made up of four core nucleic acids: adenosine,
guanosine, cytosine, and thymidine
Adenosine pairs with Thymidine
Guanosine pairs with Cytosine
We replicate DNA when we are making new cells
To do this, we unravel the DNA strands and open them up with
a protein called helicase
A protein called DNA-polymerase duplicates this DNA by
matching these
There are other proteins that doubles
DNA Replication
86
They are paired like a zipper
placing matching nucleic acids

There are other proteins that double as “spellcheckers” and
makes sure that the proper nucleic acid is matched up with its
pair
DNA Replication
87
matching these
There are other proteins that doubles
Mutations
88
Mutations are alterations in the genetic code of a cell; their
study is central to the discipline of genetics
Mutations at certain locations in the genome may affect the
organism’s resilience to stress, which can itself lead to
mutations
Mutations are random and often occur during replication they

can also happen during the process of reproductive inheritance
(production of a zygote)
Inheritance
89
Heredity is the passing-on of traits from parents to their
offspring via reproduction
Through heredity, variations between individuals can
accumulate and cause species to evolve by natural selection
Heredity plays an important role in stress vulnerability
This is the foundation of epigenetics: DNA from the parents can
be passed through to the offspring
The DNA passed is based on the parent’s CURRENT DNA
makeup (i.e. mutations and methylation)
Epigenetics
90
The genotype is the part of the genetic makeup of a cell (e.g.
genes) which determines the phenotype (e.g. proteins)
The phenotype of an organism is the composite of its observable
characteristics (traits), including its physical form, its
developmental processes and behavior
Epigenetics is the study of heritable phenotype changes which
do not involve DNA sequence alterations
Epigenetic changes often affect gene activity and expression as

a result of environmental factors, e.g. stress and aging
Types of epigenetic changes include DNA methylation and
histone modification
https://www.youtube.com/watch?v=d2ZhdT0n-8A
How DNA is read (and why it matters)
91
Not all your DNA is “readable”
Some of it is locked up away in what is known as a “histone”
These histones must be opened so that the genes may be read
and make the appropriate protein
The opening/closing of your DNA is mediated by methylation
and acetylation
That means the available genes for your body are based on this
methylation/acetylation and can be modified through epigenetic
experiences
DNA Methylation
92
A methyl group is a type of molecule containing the
–CH3 group of atoms
DNA methylation is a process whereby methyl groups are added
to DNA, thus changing DNA segment activity without changing
the actual DNA sequence
DNA methylation is a powerful suppressor of gene transcription
(the process whereby DNA is transcribed into RNA), which is

the first step of protein synthesis
Abnormal levels of DNA methylation have been implicated in
cardiovascular diseases (CVDs) like atherosclerosis, and there
is hope that DNA methylation measures could be used as early
CVD biomarkers
There is a global loss of methylation in aging, and twin studies
indicate that methylation rates diverge as a result of
environmental factors
Histone Modification and Stress
93
Histone modification refers to changes in the DNA histone
structure which will either methylate (turn off) genes or
demethylate (turn on) genes
Environmental factors play into this histone modification
Primarily, these are known as stressors (starvation, drug/alcohol
abuse, extreme temperatures, etc;)
This is a genetic “memory” of this stressor which leads to
modification of the histone aiming for “adaptation”
This “memory” is passed down to the future generation
(epigenetics) and leads to greater adaptation
Optional Reading:
Histone Methylation and Memory of Environmental
Stress(Fabrizio et. al, 2019)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523599/

We’ll see why ‘adaptation’ is in quotes
93
Stress Impact on Telomeres
94
Telomeres are cap-like structures at the ends of chromosomes
which protect them when cells divide; over time, due to ongoing
cell division, telomeres shorten
Telomere length is an indication of age and general health
Enzymes are molecules which act as catalysts to accelerate
biochemical reactions
Telomerase is an enzyme which lengthens telomeres
Stress accelerates telomere shortening; fetuses exposed to high
maternal stress have higher disease risk
Responding to stress adaptively rather than maladaptively is
crucial to a long, rewarding life
Stress, genetics, and HPA regulation
95
Prenatal stress influences HPA regulation and causes it to be
hyperactive, which leads to a greater vulnerability to abnormal
circadian rhythms, insomnia and chronic fatigue syndrome in
adulthood
Maternal stress during gestation is related to intellectual
impairment of the fetus, speech problems, attention deficits, and
disorders like autism, ADHD, depression and anxiety in
offspring
Exposure to high stress early in life increases vulnerability to
stress throughout adulthood
There is a critical period during childhood when HPA axis

calibration occurs, and if stress interferes with this then the
individual may suffer the consequences throughout her/his
entire life, including accelerated epigenetic aging
Maternal grooming affects HPA axis calibration and
epigenetically prepares the offspring to withstand stress
How genetics impacts stress response
96
Your genetics may also impact your ability to respond to stress
We have stated fetuses exposed to high levels of stress tend to
be poorly adapted to stress in life
Example: Children birthed during starvation periods are more
likely to have “thrift phenotype” which becomes a maladaptive
stress response leading to obesity, hypertension, and metabolic
syndrome (Billack et. al, 2012)
Meaning there is actual changes happening to your DNA
phenotype as a fetus due to high levels of maternal stress
impacting you as an adult
TED TALK: Ancestral Ghosts in your Genome (20:18)
PTSD Lingers in next generation (6:16)
Epigenetic Drift
97

Epigenetic drift refers to the phenomenon where the
accumulation of epigenetic changes is directly proportional to
the age of the individual
Epigenetic drift contributes to differences between
chronological age and biological age
Epigenetic drift has been found to be dependent upon lifestyle,
but lifestyle is partly predicated upon susceptibility to stress an
upon maternal stress
In genomic imprinting, both the mother and father contribute to
the epigenetic patterns at various locations in the genomes of
their germ cells
In developed countries, parental age at procreation has been
increasing steadily, and so have the incidence rates for autism,
ADHD, clinical depression, anxiety, obesity and certain cancers
Stress research suggests that these phenomena may not be
entirely coincidental
Reversibility of stress-related epigenetic aging
98
Exercise is associated with epigenetic changes which benefit
health and can assist the recalibration of the HPA axis
A healthy diet can reduce the rate of DNA methylation
Foods high in antioxidants (e.g. fruits, vegetables) contribute to
good health and can reduce the rate of epigenetic changes
Berries contain large concentrations of antioxidants and studies
have found that a berry-rich diet is beneficial to good health
Some teas (white tea, green tea, chamomile, herbal teas) but not
all (black tea) contain anti-oxidants
Chamomile tea contains several serotonin precursors which may
alleviate anxiety and improve sleep in addition to having anti -

bacterial, anti-viral and anti-inflammatory properties
Foods which are high in saturated and poly-saturated fats (e.g.
processed foods) should be avoided as they increase oxidative
stress
How to best prepare for epigenetics
99
Maternal care can contribute to the appropriate calibration of
the HPA axis to reduce offspring’s susceptibility to depression,
anxiety and accelerated aging later in life
Epigenetic biomarkers of disease risk will likely be developed
in the coming decades to assist with monitoring and reversing
deleterious health trends in the population
Epigenetic age acceleration is highly heritable in newborns but
shows markedly decreased heritability later in life, which
suggests that positive interventions can rectify the trajectory of
stress-related effects upon the offspring
Building a foundation of healthy stress responses may lead to
less histone modification
Example: instead of just “coping/dealing” with stressors seeking
stress relief through therapy, counseling, social activity,
hobbies, meditation, and exercise may be beneficial

Appraisal model of gene and environment
1
Basic Principles:
Giant feedback loop
Starts and ends with environmental disequilibrium /
accommodation
Cognition and appraisal
Coping strategies
Responses
Potential storm / stress/ accommodation equilibrium
Lazarus & Folkman (1984)
Primary Appraisals
Beliefs and commitments form the basis of appraisal
4 component attitude model
Links to personality type, LOC etc
Appraisal of benign if belief congruent
Threats require action (bio and/or psych) to eliminate
B&C explains individual difference
101

Secondary Appraisals
Adaptive responses to limit / avoid hard
Indiv. Coping strategies / behaviours
Overt coping (put sweater on)
Covert coping (adjustments related to problem and the
emotional impact – increase education about dementia)
Responses include:
Cognitive approach
Behavioural adjustments
Realignment of goals / commitments
Psychological approaches (denial etc)
Coping can be problem focused or emotion focused
102
Dynamic processes
Emotion focused – Initially less energy; long term draining on
coping recourse and minimal impact on the problem event
Problem focused – costly in energy & initial time commitment;
lower the stressor value if effective
Emotion focused (eg denial) – stress reducing with serious and
terminal illness; problem focused can be more anxiety
provoking (Kreitler, 1999)
Both strategies aim to reduce nervous system activation;
negative affect and physiological activation
When strategy used, can enter into evaluation process again
Beliefs and commitments are updated

Overall cog. Regulation over emotion and state of distress
103
An integrated approach
Basic Principles
Giant feedback loop
Incorporation of individual sensory interpretation (beliefs and
experience)
Emotional triggers for biological and psychological pathways
System appraisal of biological input on sensory intake
Biological outcomes and mediation from emotional appraisal
Starts and ends with disequilibrium / accommodation
Coping strategies reflect lifecourse & genetics
104
Week 4

[email protected]
Office: GERO 231E
Email: pnash@usc.edu
Gillian Fennell
What were the key points from last time?
106
Nature v nurture?
Influences factors for genetic predisposition
Influence of personality types
Coping mechanisms
Appraisal models
Integrated approach to genetic predisposition
107
What does depression look like
The DSM

Unipolar depression
Gender differences
Types and incidence rates
Treatment
Depression in later life
Substance misuse
What is depression?
108
What do you understand by depression?
Depression, otherwise known as major depressive disorder or
clinical depression, is a common and serious mood disorder.
Those who suffer from depression experience persistent
feelings of sadness and hopelessness and lose interest in
activities they once enjoyed. Aside from the emotional
problems caused by depression, individuals can also present
with a physical symptom such as chronic pain or digestive
issues.
DSM V
109

Five or more symptoms during the same 2-week period and at
least one of the symptoms should be either (1) depressed mood
or (2) loss of interest or pleasure.
Depressed mood most of the day, nearly every day.
Markedly diminished interest or pleasure in all, or almost all,
activities most of the day, nearly every day.
Significant weight loss when not dieting or weight gain, or
decrease or increase in appetite nearly every day.
A slowing down of thought and a reduction of physical
movement (observable by others, not merely subjective feelings
of restlessness or being slowed down).
Fatigue or loss of energy nearly every day.
Feelings of worthlessness or excessive or inappropriate guilt
nearly every day.
Diminished ability to think or concentrate, or indecisiveness,
nearly every day.
Recurrent thoughts of death, recurrent suicidal ideation without
a specific plan, or a suicide attempt or a specific plan for
committing suicide.
To receive a diagnosis of depression, these symptoms must
cause the individual clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
The symptoms must also not be a result of substance abuse or
another medical condition.
Isn't depression just being sad?
110

The difference doesn’t lie in the extent to which a person feels
down, but rather in a combination of factors relating to the
duration of these negative feelings, other symptoms, bodily
impact, and the effect upon the individual’s ability to function
in daily life.
Sadness is a normal emotion that everyone will experience at
some point in his or her life. Be it the loss of a job, the end of a
relationship etc. sadness is usually caused by a specific
situation, person, or event
A person suffering from depression feels sad or hopeless about
everything. This person may have every reason in the world to
be happy and yet they lose the ability to experience joy or
pleasure
With sadness, you might feel down in the dumps for a day or
two, but you’re still able to enjoy simple things like your
favorite TV show, food, or spending time with friends. This
isn’t the case when someone is dealing with depression. Even
activities that they once enjoyed are no longer interesting or
pleasurable.
self-harm and suicidal inclinations don’t arise from non-
depressive sadness.
Those struggling with severe depression may have thoughts of
self-harm, death, or suicide, or have a suicide plan
Major Depression (Unipolar)
111
Characterized by a persistent feeling of sadness or a lack of
interest in outside stimuli

Unipolar depression is solely focused on the ”lows,” or the
negative emotions and symptoms that you may have experienced
Major depression is well understood in the medical community
and is often easily treatable through a combination of
medication and talk therapy….. Not so with others…
How big of an issue is it…?
Even in children, according to analysis of the 2005 census, a
significant proportion are experiencing MDE’s Why? Worse
now?
…But that’s not the sum…
Gender differences
112
The lifetime incidence of depression in the United States is
more than 20-26% for women and 8-12% for men
The median age for the onset of major depression is age 32
About 7 percent of the adult U.S. population has this
debilitating mental health condition at any given time
Woman and men differ, but why?
The most commonly cited physiological reason for women
experiencing major depression more than men is due to
fluctuating hormones and genetic predisposition, particularity
around the times of puberty, childbirth, and menopause

Depression tends to co-occur with other illnesses and mental
conditions incl. pregnancy
25% of cancer patients, one third of HIV patients, and one third
of heart attack survivors suffer from major depression
Approximately 80% of patients who seek treatment for major
depression show improvement within four to six weeks
If left untreated, can have fatal results Why do people not seek
treatment?
Depression in the US
113
Types of depression
15
Postpartum depression is much more serious than the “baby
blues” (relatively mild depressive and anxiety symptoms that
typically clear within two weeks after delivery) that many
women experience after giving birth. Women with postpartum
depression experience full-blown major depression during
pregnancy or after delivery (postpartum depression). The
feelings of extreme sadness, anxiety, and exhaustion that

accompany postpartum depression may make it difficult for
these new mothers to complete daily care activities for
themselves and/or for their babies.
16% of women experience this
Persistent depressive disorder (also called dysthymia) is a
depressed mood that lasts for at least two years. A person
diagnosed with persistent depressive disorder may have
episodes of major depression along with periods of less severe
symptoms, but symptoms must last for two years to be
considered persistent depressive disorder.
About 2 % of the American population have a depression type
that's less severe than major depression, but is still very real
Types of depression
16
Psychotic depression occurs when a person has severe
depression plus some form of psychosis, such as having
disturbing false fixed beliefs (delusions) or hearing or seeing
upsetting things that others cannot hear or see (hallucinations).
The psychotic symptoms typically have a depressive “theme,”
such as delusions of guilt, poverty, or illness. Up to 20% of
people with depression experience psychosis
Seasonal affective disorder is characterized by the onset of
depression during the winter months, when there is less natural
sunlight. This depression generally lifts during spring and
summer. Winter depression, typically accompanied by social
withdrawal, increased sleep, and weight gain, predictably
returns every year in seasonal affective disorder. 4-6% of US

citizens
Bipolar disorder is different from depression, but it is included
in this list is because someone with bipolar disorder
experiences episodes of extremely low moods that meet the
criteria for major depression (called “bipolar depression”). But
a person with bipolar disorder also experiences extreme high –
euphoric or irritable – moods called “mania” or a less severe
form called “hypomania.” 2-3% population and highest risk of
suicide
Depression and health
Depression alters biological systems
Endocrine
Immune
Cardiovascular
Metabolic
Neurocognitive
Depression promotes inflammation
High inflammation associated with:
cardiovascular disease, diabetes, metabolic syndrome,
rheumatoid arthritis, asthma, multiple sclerosis, chronic pain,
psoriasis. These diseases pose an elevated risk of depression
116

Depression cycles
117
Depression can sensitize the inflammatory process
Depression and stress increase risks of infection, prolonged
infections and delayed wound healing
Difficulties with ADLs increase risk of depression
Depression predicts frailty and frailty predicts depression
Sleep cycles and depression
Distress increases risk for depression; depression affects sleep;
sleep loss stimulates production of proinflammatory cytokines,
increasing depression risk
Depression and CV Disease
118
Major depressive disorders projected to become the leading
cause of worldwide disability by 2030
Mostly due to association with diseases for reasons other than
inflammation:
Symptom burden
Psychological stress
Financial hardship
Functional limitations

Cardiovascular disorders may cause depression but depression
is also a risk factor for cardiovascular disorders in healthy
populations and predicts adverse cardiovascular outcomes
among populations with preexisting cardiovascular disorders
Whooley & Wong (2013)
Mechanisms for CV disease and depression interaction
20
Depression higher in those with cardiovascular disease than
cancer, diabetes, hypertension, arthritis, or chronic lung
disease, even 8 years after diagnosis
Physical activity accounts for most of the risk of
cardiovascular mortality due to depressive symptoms (32%)
Medication non-adherence accounts for some of the risk due to
depression (5%)
Smoking may be a form of self-medication & smoking may
cause neurologic changes in the systems that can lead to
depressed mood. It accounts for 10% of the risk of
cardiovascular mortality due to depression.
Treating Depression - Psychotherapies

21
Interpersonal therapy is relatively short in duration. Sessions
are highly structured. It's based on the idea that your
relationships are at the forefront of depression. The goal of
treatment is to help patients improve skills, such as
communication skills and conflict- resolution skills.
Social skills therapy teaches patients how to establish healthy
relationships. The goal is for patients to improve
communication and learn how to build a strong social network
with individuals based on honesty and respect.
Cognitive behavioral therapy focuses on helping people
identify and replace cognitive distortions and behavioral
patterns that reinforce depressive feelings. It is usually short-
term and it focuses on present problems and skills teaching.
Psychodynamic therapy is often featured in movies or pop
culture. It involves helping patients explore their unconscious
and unhealed emotional wounds from the past.
The goal is to help people learn how their depression is related
to past experiences and unresolved conflicts. The therapist
helps patients address those issues so they can move forward
in a productive manner.
Treating Depression - Psychotherapies
22
Supportive counseling is unstructured and focuses on listening
to the patient. Patients are invited to address whatever issues
they want to talk about and the therapist uses empathy to
provide understanding and support

Behavioral activation raises awareness of pleasant activities.
The therapist seeks to increase positive interactions between
the patient and the environment. By getting active and
engaging in more pleasurable activities, symptoms of
depression may be reduced
Problem-solving therapy aims to define a patient's problems.
Then, multiple solutions are offered. The therapist helps the
patient evaluate options and choose a solution
Treating Depression – Pharmaceutical
23
There are many different medications that can help reduce the
symptoms of depression. Most studies have found medication is
most effective when it is used in conjunction with therapy
Tricyclic antidepressants (TCAs) — were among the first
developed antidepressants. They have more side effects than
newer antidepressants but can be more effective
for certain patients. These include Elavil (amitriptyline),
Tofranil (imipramine) and Pamelor (nortriptyline)
Monoamine oxidase inhibitors (MAOIs) — are another older
type of antidepressant. If you are taking an MAOI, you will
have to follow certain dietary restrictions to prevent a reaction
that can cause high blood pressure. You will also have to be
careful about interactions with certain other medications. Like
tricyclics, these are not generally used first line, but can
sometimes be helpful for more difficult to treat depressions.
MAOIs include Marplan (isocarboxazid), Nardil (phenelzine)
and Parnate (tranylcypromine)

Selective serotonin reuptake inhibitors (SSRIs) — are the most
commonly prescribed medication for depression today. Prozac
(fluoxetine), Paxil (paroxetine), Zoloft (sertraline) Celexa
(citalopram) and Luvox (fluvoxamine) are commonly
prescribed brand names. Compared to other antidepressant
types, SSRIs tend to have fewer side effects. SSRIs should not
be prescribed in conjunction with the older MAOIs due to the
potential for a dangerously high level of serotonin to build up,
which can cause serotonin syndrome.
Treating Depression – Pharmaceutical
123
Norepinephrine and dopamine reuptake inhibitors (NDRIs) —
Wellbutrin (bupropion) is in a class all by itself. Wellbutrin is
less likely to have the sexual side effects that are common in
the other antidepressants.
Serotonin and norepinephrine reuptake inhibitors (SNRIs) —
are a newer type of antidepressant that works similarly to
SSRIs only they also block the reuptake of norepinephrine
along with serotonin. Common medications in this class are
Effexor (venlafaxine), Cymbalta (duloxetine) and Pristiq
(deslavenfaxine).

Something a little different…
124
https://www.washingtonpost.com/national/health-science/a-one-
time-party-drug-is-helping-people-with-deep-
depression/2016/02/01/d3e73862-b490-11e5-a76a-
0b5145e8679a_story.html?noredirect=on&utm_term=.09a40627
d095
Ketamine works differently from traditional antidepressants,
which target the brain’s serotonin and noradrenalin systems. It
blocks N-methyl-D-aspartate (NMDA), a receptor in the brain
that is activated by glutamate, a neurotransmitter.
“Ketamine almost certainly modifies the function of synapses
and circuits, turning certain circuits on and off,” explains
Carlos Zarate Jr., NIMH’s chief of neurobiology and treatment
of mood disorders, who has led the research on ketamine. “The
result is a rapid antidepressant effect.”
A study published in the journal Science in 2010 suggested that
ketamine restores brain function through a process called
synaptogenesis. Scientists at Yale University found that
ketamine not only improved depression-like behavior in rats
but also promoted the growth of new synaptic connections

between neurons in the brain.
This drug is 75 percent effective
Depression in later life
125
Major depression - less common than at any other stage of life
However… isolated symptoms are much more frequent
PROJ592 Project Proposal Sample
Course Project Part 1
Instructions: After completing the assignment below, post a
document with the required information using this filename
convention:
PROJ592_Week1_ProjectProposal_yourlastname.docx.
For detailed grading information, refer to the Course Project
area in the Introduction and Resources module.

Project Concept
Instructions:
After selecting your project topic, provide a description of your
project. For instance: “The goal of this project is to produce a
blockbuster movie based on the life of Buckminster Fuller, the
famous architect, author, designer, theorist, and inventor.”
Proposed Timeline
Instructions:
Using MS Project, create a first-level work breakdown,
including major deliverable milestones and preliminary resource
inputs. Then, insert the timeline into the Word document.
Budget
Instructions:
This section should include a preliminary estimate of the budget
for the movie. For instance, if you were making a movie, you
would need to have an idea of staff costs (director, actors, grips,
etc.) as well as productions costs (location costs, set
construction, film). Put your preliminary resources into MS
Project and then insert the resource report into your proposal
document.
Benefits
Instructions:
This section should discuss the benefits from the project. In
other words, why you are proposing the project. For instance,
how much money do you expect to make? What is the expected
return on investment? What is the social impact? The benefits
will depend on the type of project proposed.
Action Request
Instructions:
What is it that you are asking for? In this case, it is the
professor’s approval.

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