This document provides information about depression, stress, and anxiety. It discusses the criteria for diagnosing major depression according to the DSM-IV-TR. It notes that depression can be caused by genetic and environmental factors, and describes research showing that early life stress and trauma can influence gene expression and increase the risk of depression through adulthood. The document also discusses the effectiveness of antidepressant medication and the brain mechanisms by which stress gets "under the skin" to impact long-term health.

1. Slide 1
Working on the Inside
Stress, Depression, and Anxiety
HEA 325
Slide 2
Remember what stresses us out!
Slide 3
A Circle of Influence
NOTE THAT THESE THREE REALLY CAN’T BE SEPARATED
Slide 4
Depression
• What is depression?
• How is it identified?
• What appears to cause it?
• What is the relationship between stress
and depression?
• What are some techniques to manage it?
• What are the relationships between
depression and anxiety?
Slide 5
DSM-IV-TR Criteria
• Major depression is present when the
patient has had at least 5 of the 9 following
persistent symptoms for a minimum of two
weeks. One of the symptoms must be
either:
• 1. Depressed mood (most of the day, nearly
every day) or
• 2. Markedly Diminished Interest or
Pleasure (anhedonia) (in almost all activities)
Slide 6
• 3. Significant change in weight or appetite
• 4. Insomnia or hypersomnia
• 5. Psychomotor agitation or retardation
• 6. Fatigue or loss of energy
• 7. Feelings of worthlessness or guilt
• 8. Impaired concentration or ability to
make decisions
• 9. Thoughts of suicide or self-harm
Slide 7
Types of Depression
• Major Depression: the most severe and frequent type of depression.
• You do not need to feel suicidal to have a major depression.
• There is no official diagnosis of "moderate depression“ or “mild depression.”
• Dysthymic Disorder: a low to moderate level of depression that persists for at least
• two years. The symptoms are not as severe as a major depression, though are more
• resistant to treatment
• Unspecified Depression:
• people with a serious depression, but not quite severe enough to have a diagnosis of
• a major depression
• people with chronic, moderate depression, which has not been present long enough
• for a diagnosis of a Dysthymic disorder
• Adjustment Disorder with Depression: This category describes depression that
• occurs in response to a major life stressor or crisis
• Bipolar Depression: This type includes both high and low mood swings, as well as a
• variety of other significant symptoms not present in other depressions

2. Slide 8
Bipolar Disorders
• History of at least 1 MD Episode
• Presence of 1 manic or hypomanic episode (3
or more)
– Abnormally elevated mood
– Grandiosity
– Decreased need for sleep
– Talkativeness/ Flight of ideas
– Distractibility
– Psychomotor agitation
– Excessive involvement in pleasurable activities
Slide 9
Statistics
• Spending on antidepressants jumped 150% from 1997 to
2004;
• Depression affects approximately 18.8 American adults
(9.5% of the adult population);
• 15% of the population of most developed countries
suffers severe depression;
• 15% of depressed people will commit suicide;
• The World Health Organization forecasts depression will
be the second largest killer after heart disease by 2020;
• Nearly two-thirds of depressed people do not get proper
treatment.
Slide 10
Prevalence of Mental Illness
reported10-19-09
Slide 11
Famous People with Depression
• Woody Allen (film director)
• • Ingmar Bergman (film director)
• • Albert Camus (writer)
• • Jim Carrey (actor)
• • Sheryl Crow (musician)
• • Fyodor Dostoevsky (writer)
• • Vincent Van Gogh (painter)
• • Ernest Hemingway (writer)
• • Abraham Lincoln (16th President of US)
• • Martin Luther (priest and theologian)
• • Michelangelo (painter and sculptor)
• • Isaac Newton (physicist)
• • Friedrich Nietzsche (philosopher)
• • Mark Twain (writer)
Slide 12
Famous People with Anxiety
• • Anthony Hopkins (actor)
• • Barbra Streisand (singer)
• • Abraham Lincoln (president)
• • David Bowie (singer)
• • Edvard Munch (artist)
• • Eric Clapton (musician)
• • Johnny Depp (actor)
• • Nicholas Cage (actor)
• • Nicole Kidman (actress)
• • Oprah Winfrey (host)
• • Sigmund Freud (psychiatrist)
• • Sir Isaac Newton (scientist)
Slide 13
A disorder with a high rate of
relapse.
50% of Individuals who have had an episode
of major depressive disorder will have
another episode.
Of those who have had two episodes,
75% will have a third.
Slide 14 Same pattern in samples from France, Germany, and Canada. US sites included white and non-white groups.
AGE

3. Slide 15
Gender Differences
Slide 16
Seasonal Affective Disorder
Slide 17
Is Depression “in your genes”?
NOT EXACTLY….
Slide 18
Genetic heritability for depression
is substantial…
(This means that our genes do make some
contribution to depression, but….)
Genes don’t do this alone!
Slide 19
Two Buckets v. Mud Pie View
NATURE
Versus
NURTURE
Slide 20
Slide 21
Epigenetic Modification
• This means a change in gene expression
that is caused by
something other than a change in the
underlying DNA sequence

4. Slide 22
HOW GENES WORK
Transcription Translation Folding
DNA mRNA Polypeptides Proteins
Impact of transacting
factors, Influenced by other
enhancers and genes and cell
silencers (all made up environments
of DNA)
}
Genetic influences Environmental influences and
chance effects
Gene Expression
Slide 23
• Genes just don’t operate by themselves –
they get activated (turned-on) or de-
activated (silenced) by environmental
influences!
Slide 24
What’s the process?
• Most well-studied epigenetic mechanism =
methylation of cytosine on the DNA;
• If methylation occurs in an active stretch of
DNA, especially a promoter region, gene
expression will likely change.
Slide 25
Slide 26
Slide 27
This phenomenon is called:
• Epigenetics
• Gene - Environment interaction
• GXE
What’s new about this?
– It does not only occur during basic fetal
development, when cells are
specializing……it can continue after birth and
be influenced by the broader environment!
Slide 28
What’s the news?
Nature Versus Nurture Nature X Nurture
Gene-Environment
Genes versus Environment
Interaction

5. Slide 29
Relation to Early Experience
Meaney et al
• Low Maternal Care
– Higher and more prolonged
CORT responses in
adulthood
– Higher CRF activity
– Higher brain NE activity
– Less Brain production of
stress modulators: e.g
natural opiates
– More fearful/anxious
behavior
– Poorer memory; effects on
learning/memory systems
Maternal Care in Adult Outcomes of
Rodents Poor Maternal Care
Slide 30
Maternal behaviour, methylation
and pup behavior
• Some rat pups inherit a gene variant for cortisol that
can make them anxious. At birth it is unmethylated.
• If the rat pup is licked a lot in the first six days, a
single methyl group (CH3) becomes attached at one
specific location on the DNA in brain cells.
• This makes it impossible for the gene to be
transcribed. The gene is silenced by the mother rats
behaviour and the rat pup is placid.
• Remove the methyl group (can be done chemically)
and the rat pup reverts to being anxious, consistent
with its genotype.
Slide 31
Licking and stress response
• The pups with the gene predisposing them
for a more anxious response but who are
nursed in this way are less fearful.
• They produce less stress hormones when
provoked.
• Their heart rate doesn't go up as much.
• The licking/arch back nursing had to have
occurred in the first six days of life.
This is now known to be an example of
epigenetics
Slide 32 GENE-ENVIRONMENT INTERACTION IN
LIABILITY TO ANTISOCIAL BEHAVIOR
(From Cadoret, Cain & Crowe, 1983)
5 5
4 4
Average
number of
3 3
antisocial
behaviors
2 2
1 1
0 0
GENETIC FACTOR: Absent Absent Present Present
ENVIRONMENTAL: Absent Present Absent Present
FACTOR
Slide 33
Gene-Environment Interaction:
SCHIZOPHRENIA SPECTRUM DISORDER:
with CANNABIS USE (Caspi et al., 2005)
20 COMT genotype
Met/Met
%schizophreniform disorder
Met/Val
15 Val/Val
10
5
0
No adolescent use Adolescent use
Slide 34
What gene is important to stress
and depression?
5-HTT Serotonin Transporter
Slide 35
Important Neurotransmitter
Systems
Movement
Ideation
Pleasure

6. Slide 36
Slide 37
The Long and Short of It
Combinations:
Long-Long (BEST)
Long-Short
Short-Short (WORST)
Slide 38 Gene-Environment Interaction:
EFFECT OF LIFE STRESS ON DEPRESSION
MODERATED BY 5-HTT GENE (from Caspi et al., 2003)
.50
s/s = short allele homozygous
s/s
l/l = long allele homozygous
.40
s/l = heterozygous
Probability of major
depression episode
.30 s/l
.20
l/l
.10
.00
0 1 2 3 4+
Number of stressful life events
Slide 39 GxE: Interaction of HTTLPR and stress in depression
Caspi et al, Science 2003
Slide 40 The Interaction Between Genetics and
Experience: The case of early abuse
Depression
Risk
.70
SS
S = short allele
L = long allele
.50
SL
.30 LL
No Abuse Moderate Abuse Severe Abuse
Early Childhood Experience
Source: Caspi (2003)
Slide 41 Predictors of depression
Kaufman J et al. PNAS 2004;101:17316-17321
©2004 by National Academy of Sciences
Slide 42
Early Childhood Adversity Can Influence
a Range of Lifelong Outcomes
Research on the biology of stress helps
explain some of the underlying causal
mechanisms for differences in learning,
behavior, and physical and mental health.

7. Slide 43
The Adverse Childhood Experiences (ACE) Study:
• Recurrent physical abuse
• Recurrent emotional abuse
• Contact sexual abuse
• An alcohol and/or drug abuser in the
household
• An incarcerated household member
• Someone who is chronically depressed,
mentally ill, institutionalized, or suicidal
• Mother is treated violently
• One or no parents
• Emotional or physical neglect
Slide 44
Risk Factors for Adult Depression are
Embedded in Adverse Childhood Experiences
5
4
Odds Ratio
3
2
1
0 1 2 3 4 5+
ACEs Source: Chapman et al, 2004
Slide 45
Risk Factors for Adult Heart Disease are
Embedded in Adverse Childhood Experiences
3.5
3
Odds Ratio
2.5
2
1.5
1
0.5
0 1 2 3 4 5,6 7,8
ACEs Source: Dong et al, 2004
Slide 46
How does early life stress “get under the
skin” to affect life-long health?
Slide 47
The Stress System
CORTISOL feedback
to the
Brain
Slide 48
Influence of Cortisol
• Steroid hormone goes through the cell wall into
the cytoplasm where it binds to receptor. Then
these complexes go into the nucleus, attach to
DNA and tell DNA to increase or decrease the
gene expression.
• Gene for cortisol receptor gets TURNED DOWN
(Thermostat is off, and it doesn’t give the signal
to the body that there is too much cortisol.)
• Inflammatory processes stay high.
Slide 49
Influence of Cortisol
• Cortisol actually damages the hippocampus
causing cell death.
• Hippocampus is smaller in depressed people
(average is 10-18% smaller than in non-
depressed people)
• When you start losing hippocampal cells, you
have less regulation of the HPA axis.
• The hippocampus is actually like a “brake” on
the system. Loss of cells is like your car’s brakes
getting worn down.
• The HPA axis is more reactive.

8. Slide 50 This figure shows data reported by Bunney et al (1969)
who found very high cortisol levels in depressed patients
who subsequently committed suicide.
Slide 51
Institutionalization and Neglect of Young
Children Disrupts Their Body Chemistry
35%
Percent of
Children 30%
with
Abnormal 25%
Stress
Hormone 20%
Levels
15%
10%
5%
Middle Class US Toddlers Neglected/Maltreated Toddlers
in Birth Families Arriving from Orphanages Overseas
Source: Gunnar & Fisher (2006)
Slide 52
Stress gets under your skin
• Stressors trigger the first few episodes.
• Subsequently, depression can occur
regardless of the presence of stressors.
• Called “stress-sensitization” or “kindling-
sensitization.”
Slide 53
Example of Seizure Study with
Animals
• Animals – initially given a drug that could
cause a seizure – have no seizure;
• But if you keep giving the low dose,
eventually the brain get “sensitized”;
• There is a seizure;
• This is a MODEL FOR DRUG
SENSITIZATION
Slide 54
The depressed brain
Kindling-Sensitization Theory
With each episode of depression, the neurotransmitter
systems become more easily dysregulated.
FIRST
STRONG STRESSOR EPISODE
MILDER SUBSEQUENT
STRESSORS EPISODES
Slide 55
Antidepressant Info
• Normally it takes 14-30 days for the patient to
benefit from the drug, called “Therapeutic lag”.
• During this time, risk of suicide is high.
• All drugs have side effects.
• Effectiveness differs for severe v. moderate
cases
– Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria
A, Moore TJ, et al. (2008) Initial Severity and
Antidepressant Benefits: A Meta-Analysis of Data
Submitted to the Food and Drug Administration. PLoS
Med 5(2): e45 doi:10.1371/journal.pmed.0050045
Slide 56
How effective is medication?
• Protect the hippocampus against further
cell damage.
• Relieves moderate/severe depression for
some people.
Prozac, Serzone, Wellbutrin, Zoloft, Remeron, Celexa, Effexor, Lovox, Paxil

9. Slide 57
How effective is medication?
According to testimony given in the fall of 2004
to the Congressional Energy and Commerce
Committee, about half of all studies of anti-
depressants have not shown in adults that the
SSRI drugs are significantly more effective than
a placebo alone. Even worse, insignificant
results were found in two thirds of the studies in
which children were given anti-depressants and
compared to children given a placebo.
Slide 58
How effective is medication?
On September 10, 2004, testimony was
given at a congressional meeting that two
internal FDA analyses showed that anti-
depressants, given to children and
teens, were associated with increased
suicidal thoughts, actual self-harm, and
hostile behavior.
Slide 59
Some conclusions
• The chemical imbalance theory of depression
has not been proven. The “cause” of depression
is unknown.
• Stress is clearly related to depression.
• Medication can change the brain, but so can
thinking and acting.
• Antidepressant medication is ineffective for 40 to
50% of people.
• Therapies and cognitive-behavioral changes
have been shown to be more effective with
moderate to mild cases. In severe cases,
medication plus therapy is most effective.
Slide 60
Views of Depression and
Treatments for Depression and
Depressogenic Thinking
• Cognitive Approaches (Target the
thinking)
• Mindfulness Approaches (Letting go)
• Exercise (Reducing the stress response)
• Diet (Reducing inflammatory processes)
• Social Support
Slide 61
Anxiety
Negative HPA axis
Thinking
Chronic
Stress Helplessness
Response Sad Mood Cytokine
Activation
OVERLOAD
Hopelessness
Lowered
Motivation
Sickness
Cortisol
Behavior
Goes Up
Sleeping/
Eating
Problems
Slide 62
What am I
doing
to deserve Why can’t
this? I handle
Why do
things
I always
better?
react this way?
Why do I have What else is
problems other
going on in
people don’t have?
my life?
Slide 63
Learned Helplessness
A theory of depression that states that
people become depressed when they
perceive that they
1) no longer have control over the
rewards and punishments in their life
2)they are responsible for this helpless
state.

10. Slide 64
Learned Helplessness:
Martin Seligman
Slide 65
Beck’s Negative Cognitive Triad
SL
EF
H ow
Dpre d
e sse
Individuals
Think
about …
W RD
OL F TU E
U R
Slide 66 Rumination Triggers the Brain’s
Network of Associations
Unloved
Uncaring
Hopeless
Mean
Cold Sadness
Unattractive
Worthless
Awkward Failure
Clumsy Stupid
Slide 67
What to Avoid: Cognitive
Distortions
• Thought (or pattern of thoughts) that
contributes to our unhappiness and
undermines mental health;
• Thought (or pattern of thoughts) that
colors perceptions of what happens to us
in our life;
• Thought (or pattern of thoughts) that
affects our moods and behaviors;
Slide 68
Albert Ellis Aaron Beck
Rational-Emotive Cognitive Therapy
Therapy (RET) (CT)
Slide 69 Aaron Beck’s Model of
Emotional Disturbance
OR – HOW THOUGHTS MAKE US SICK!
Activating Automatic Emotional
Event Thought Consequence
Slide 70
My date I bore
yawns Sad
Everybody!
A B C

11. Slide 71
Different Interpretation, Different
Feeling!
Slight
My date she doesn’t
yawns sympathy
sleep well
for date
Slide 72
Another Example-
Let’s Include Behavior
Turned
down I’m a freak;
I’ll die single Despondent
for date
Sleeps all
weekend
Slide 73
A healthier interpretation
Turned down that’s the
Slightly
for date dating world
disappointed
for you
I’ll try
Match.com!
Slide 74 Some Types of Automatic
Thoughts: Cognitive
Distortions
• All-or-nothing thinking
• Overgeneralization
• Mental Filter
• Disqualifying the Positives
• Mind Reading
• Catastrophizing
• Magnification or Minimization
• Emotional reasoning
• “Should” statements
• Labeling/Mislabeling
• Personalization
• Maladaptive Thoughts
• Compensatory Misconceptions
Slide 75
Identify the distortions
• Michelle is upset that Richard is late. Her
thoughts are:
• “What a jerk! He’s never on time. If he
cared about me, he wouldn’t be so late.
He should be home by now.”
Slide 76
Identify the distortions 2
• Brenda has been trying to diet. This
weekend, she’s been nervous and,
because she doesn’t have anything to do,
has been nibbling. After her 3rd candy bar,
she thinks “I just can’t control myself. My
dieting has gone down the drain. I must
look like a balloon after what I’ve done! I
can’t stand this. I’m just going to pig out all
weekend.”
Slide 77
Identify the distortions 3
• Jennifer, a depressed student trying to
study for finals, thinks:
• “What’s the use in trying to study? My
mind will just wander like yesterday. I
can’t remember anything I read. I can’t
possibly read 200 pages this week, so
what’s the point?”

12. Slide 78
Daily Thought Record
Automatic Distortions Rational
Thoughts: Response
My mind will
just wander like
yesterday.
I can’t
remember
anything I read.
I can’t possibly
read 200 pages
this week…
Slide 79
Really
getting to the bottom
• Understanding
and identifying
core beliefs.
Slide 80
Self-Schema
• The cognitive structure that is
hypothesized to contain a person’s
knowledge about himself or herself
• Your own personal collection of core
beliefs
Slide 81
Core
Belief
Activating Automatic Emotional
Event Thought Consequence
Slide 82
I’m
Incompetent
( Core Belief )
Difficulty
I’ll never Feeling
Understanding
get this! Miserable
Math Text
( Activating ( Automatic ( Emotional
Event ) Thought ) Consequence )
Slide 83
Helpless Core Beliefs
• I am powerless • I am inadequate
• I am weak • I am incompetent
• I am trapped • I am a failure
Slide 84
Unlovable Core Beliefs
• I am unwanted • I am unworthy
• I am bad • I am different
• I am undesirable • I’ll be abandoned

13. Slide 85
Kyle: What is his core belief?
• Situation 1: Talking to other students
about advanced courses
– Automatic Thought: “They’re all smarter than
me.”
• Situation 2: Thinking about required
research paper for a course
– Automatic Thought: “I won’t be able to do it.”
• Situation 3: Reflecting on the difficulty of a
math text
– Automatic Thought: “I’ll flunk this course.”
Slide 86
Beth: What is her core belief?
• Situation 1: Thinking of suggesting group
trip to the beach
– Automatic Thought: “No one ever likes my
ideas.”
• Situation 2: With friends who are ordering
another pitcher of beer
– Automatic Thought: “They’ll all be annoyed if
I say I don’t want another beer.”
• Situation 3: Declining invitation to dance
– Automatic Thought: “Everyone here can
dance. I’m such a loser.”
Slide 87
Low Frustration Tolerance
• Rational belief: “I don’t like existing conditions.”
• Irrational belief: “Existing conditions must
change to give me what I like, otherwise I can’t
stand it and I can’t be happy at all!”
• Rational belief: “I would like immediate
gratification.”
• Irrational belief: “I must have immediate
gratification, or else my life is awful!”
• Rational Belief: “I find frustrations and hassles
inconvenient.”
• Irrational Belief: “I can’t stand hassles!”
Slide 88 Some Ways to Working with
Irrational Beliefs & Cognitive
Distortions
• Examine the Evidence for Plausibility
• Reattribution
• Challenging Absolutes (Disputation)
• Semantic Method
• Labeling Distortions
• Self-Monitoring Techniques
Slide 89
Another DTR Form
Situation Emotion Automatic Core Rational Outcome
Thought Belief Thought/
Response
Slide 90
Different perspectives
• Cognitive Therapy • Mindfulness
Intervention Intervention
Slide 91 Challenging the
Challenging
Specific Thoughts Nature of
thought
AWARENESS
In service of Degree of belief
changing is not
the degree something to
of Belief worry about

14. Slide 92
“It’s not about changing the degree
of belief... Not saying that if you
change the degree of belief in a
thought it will no longer be a
problem. To the extent that you
can see your thoughts as objects
that arise in a context dependent
on moods and events, you can hold
them in a different way than if you
were tied into propositions.”
Z. Segal
Slide 93
Slide 94
Allow you r thou ghts to be like w riting on
w ater.