Mood Disorders
Mood Disorders
 Two key emotions on a continuum:
Depression
Mania
• Depression
• Low, sad state in which life seems dark and
overwhelming
• Mania
• State of breathless euphoria and frenzied energy
Slide 2
Mood Disorders
 Most people with a mood disorder experience only
depression
• This pattern is called unipolar depression
• Person has no history of mania
• Mood returns to normal when depression lifts
 Some people experience periods of depression that
alternate with periods of mania
• This pattern is called bipolar disorder
Slide 3
Mood Disorders
 These disorders have always captured
people’s interest
• Millions of people have mood disorders
• Economic costs of mood disorders amount to
more than $40 billion each year
Slide 4
Unipolar Depression
 The term “depression” is often used to
describe general sadness or unhappiness
• This usage confuses a normal mood swing with a
clinical syndrome
 Clinical depression can bring severe and long-
lasting psychological pain that may intensify
over time
Slide 5
How Common Is Unipolar
Depression?
 5 to 10% of the U.S. population experiences
severe unipolar depression each year
• An additional 3 to 5% experience mild depression
 ~17% of the world population experiences
unipolar depression at some time in their lives
• Rates have been steadily increasing since 1915
Slide 6
How Common Is Unipolar
Depression?
 In almost all countries, women are twice as likely as
men to experience severe unipolar depression
• Lifetime prevalence: 26% of women vs. 12% of men
 These rates hold true across socioeconomic classes
and ethnic groups
 ~50% recover within six weeks, some without
treatment
• Most will experience another episode at some point
Slide 7
What Are the Symptoms of
Depression?
 Symptoms may differ dramatically from person to
person
 Five main areas of functioning may be affected:
• Emotional symptoms
• feeling “miserable,” “empty,” “humiliated”
• Motivational symptoms
• lack drive, initiative, spontaneity
• 6 to 15% of those with severe depression commit suicide
Slide 8
What Are the Symptoms of Unipolar
Depression?
 Five main areas of functioning may be
affected:
• Behavioral symptoms
• less active, less productive
• Cognitive symptoms
• hold negative opinion of themselves
• blame themselves for unfortunate events
• Physical symptoms
• headaches, dizzy spells, general pain
Slide 9
Diagnosing Unipolar Depression
 Criteria 1: Major depressive episode
• Marked by five or more symptoms lasting two or
more weeks
• In extreme cases, symptoms are psychotic, including
• Hallucinations
• Delusions
 Criteria 2: No history of mania
Slide 10
Diagnosing Unipolar Depression
 Two diagnoses to consider:
• Major depressive disorder
• Criteria 1 and 2 are met
• Dysthymic disorder
• Symptoms are “mild but chronic”
• Experience longer-lasting but less disabling depression
• Consistent symptoms for at least two years
• When dysthymic disorder leads to major depressive
disorder, the sequence is called “double depression”
Slide 11
What Causes Unipolar Depression?
The Biological View
 Biochemical factors
• NTs: serotonin and norepinephrine
• In the 1950s, medications for high blood pressure were
found to increase depression
• Some lowered serotonin, others lowered norepinephrine
• Led to “discovery” of effective antidepressant medications
• It is likely not just one NT or the other – a complex
interaction is at work
Slide 12
What Causes Unipolar Depression?
The Biological View
 Biochemical factors
• Endocrine system hormone release
• People with depression have been found to have
abnormal levels of cortisol
• Released by the adrenal glands during times of stress
• People with depression have been found to have
abnormal melatonin secretion
• “Dracula hormone”
Slide 13
Cognitive Deficits in Depression
 Deficits in explicit verbal and visual memory,
but not implicit memory
• Could be related to hippocampal volume
 Impairment in executive tasks
• Verbal fluency
• Set shifting
• Motor speed
Slide 14
Cognitive Deficits in Depression
It may be that depressed patients have more
difficulty with “effortful” as compared to
“automatic” tasks
Motivational factors, particularly lack of reward
sensitivity, may play a role
Some cognitive deficits improve when there is
inter-episode recovery, but there are still some
“cognitive” scars (executive functioning, some
types of memory)
Slide 15
Cognitive Deficits in DepressionLimitations
“Localising” neuropsychological tests may actually
involve a number of brain regions
Medication history
Hx of symptoms
Slide 16
Endophenotypes
Children with a first-degree relative with mood
disorder
Verbal learning and suspectibility to interference
Contradictory
EF demands
Social reasoning?
Interaction with other biological factors (e.g.,
thyroid dysfunction)
Slide 17
Tissue volume loss
Hippocampus: results are contradictory
* Age
* Medication history
* Number of episodes
* Genetic factors
* Levels of circulating cortisol
Slide 18
Tissue volume loss
Orbitofrontal cortex and amygdala
* very preliminary
* affective processing
Dorsolateral prefrontal cortex
* also preliminary
* cognitive processing
Drug effects
Cortisol
Slide 19
Mayberg model of depression
Slide 20
Goldapple et al. (2004)
 2 groups: 18 unmedicated, unipolar
depressed outpatients and 13 patients
treated with drug (anti-depressant SSRI)
 CBT
 Drug
 Both approaches equally effective: 50 percent
success rate
Slide 21
Goldapple et al. (2004)
 Cognitive behavior therapy is thought of
as a top-down approach because it focuses
on using thinking functions to modulate
abnormal mood states, modify attention
and memory functions, change affective bias,
and correct maladaptive information
processing
Slide 22
Goldapple et al. (2004)
 CBT: successful treatment increases in
cognitive processing regions (e.g.,
hippocampus) and decreases in emotional
processing areas (e.g., ventral medial cortex)
Slide 23
Goldapple et al. (2004)
 Drug therapy is seen as a bottom-up
approach because it first changes the
chemistry in the brainstem, limbic, and
subcortical sites system.
 It then produces secondary cortical changes
with chronic treatment, altering more basic
emotional and circadian behaviors and
eventually causing “upstream” changes
in depressive thinking.
Slide 24
Goldapple et al. (2004)
 With drug therapy, metabolism (blood flow)
decreases in the limbic area and increases in
the cortical area.
 With CBT, limbic increases (in the
hippocampus, dorsal mid cingulate) and
cortical decreases (in the dorsolateral,
ventrolateral, and medial orbital frontal;
inferior temporal and parietal).
Slide 25
Goldapple et al. (2004)
 As CBT patients learn to turn off the thinking
paradigm that leads them to dwell on negative
thoughts and attitudes, activity in certain
areas in the cortical (thinking, attention)
region are decreasing as well.
 Drug leads to increases in cognitive oversight
and decreases in ruminative, negative mood
states
Slide 26
Goldapple et al. (2004)
2 types of depressed patients
Differ at baseline
Slide 27
Lobotomy’s back!
Slide 28
Anterior cingulotomy
 Advances in neurosurgical equipment and
techniques allow for new approaches to
treating psychiatric problems
 Researchers have demonstrated that
psychosurgery has helped a considerable
number of treatment-resistant patients (low
n)
Slide 29
Counterpoint
 Withholding psychosurgery becomes
ethically questionable for severely ill,
treatment resistant patients
 A theoretical justification is not required for
the ethical use of psychosurgery, only
adequate demonstrations of safety and
efficacy (effectiveness) ???
Slide 30
Bipolar Disorders
 People with a bipolar disorder experience
both the lows of depression and the highs of
mania
• They describe their life as an emotional roller
coaster
Slide 31
What Are the Symptoms of Mania?
 Unlike those experiencing depression, people in a
state of mania typically experience dramatic and
inappropriate rises in mood
 Five main areas of functioning may be affected:
1. Emotional symptoms
• active, powerful emotions in search of outlet
2. Motivational symptoms
• need for constant excitement, involvement, companionship
Slide 32
What Are the Symptoms of Mania?
 Five main areas of functioning may be affected:
• Behavioral symptoms
• very active – move quickly; talk loudly or rapidly
• Key word: flamboyance!
• Cognitive symptoms
• show poor judgement or planning
• Especially prone to poor (or no) planning
• Physical symptoms
• high energy level – often in the presence of little or no rest
Slide 33
Diagnosing Bipolar Disorders
 Criteria 1: Manic episode
• Three or more symptoms of mania lasting one
week or more
• In extreme cases, symptoms are psychotic
• Criteria 2: History of mania
• If currently experiencing hypomania or depression
Slide 34
Diagnosing Bipolar Disorders
 Two kinds of bipolar disorder:
• Bipolar I disorder
• Full manic and major depressive episodes
• Most sufferers experience an alternation of
episodes
• Some experience mixed episodes
• Bipolar II disorder
• Hypomanic episodes and major depressive episodes
Slide 35
Diagnosing Bipolar Disorders
 Without treatment, the mood episodes tend to
recur for people with either type of bipolar
disorder
• If people experience four or more episodes within
a one-year period, their disorder is further
classified as rapid cycling
• If their episodes vary with the seasons, their
disorder is further classified as seasonal
Slide 36
Diagnosing Bipolar Disorders
 Between 1 and 1.5% of adults in the world
suffer from a bipolar disorder at any given
time
 The disorders are equally common in women
and men
• Women may experience more depressive and
fewer manic episodes than men
• Rapid cycling is more common in women
Slide 37
What Causes Bipolar Disorders?
 Neurotransmitters (NTs)
• After finding a relationship between low
norepinephrine and unipolar depression, early
researchers expected to find a link between high
norepinephrine and mania
• This theory is supported by some research studies;
bipolar disorders may be related to overactivity of
norepinephrine
Slide 38
What Causes Bipolar Disorders?
 Neurotransmitters (NTs)
• Because serotonin activity often parallels
norepinephrine activity in unipolar depression,
theorists expected that mania would also be
related to high serotonin activity
• While no relationship with HIGH serotonin has been
found, bipolar disorder may be linked to LOW
serotonin activity, which seems contradictory…
Slide 39
What Causes Bipolar Disorders?
 Neurotransmitters (NTs)
• This apparent contradiction is addressed by the
“permissive theory” about mood disorders:
• Low serotonin may “open the door” to a mood
disorder and permit norepinephrine activity to define
the particular form the disorder will take:
• Low serotonin + Low norepinephrine = Depression
• Low serotonin + High norepinephrine = Mania
Slide 40
What Causes Bipolar Disorders?
 Ion activity
• Ions, which are needed to send incoming
messages to nerve endings, may be improperly
transported through the cells
• This improper transport may cause neurons to fire
too easily (mania) or to resist firing (depression)
• There is some research support for this theory
Slide 41
Hippocampal volume INCREASES
 We have reported increases in hippocampal volume
in BD patients both cross-sectionally
and prospectively
 Lithium
 Other antipsychotics
 No drug
 Control
Slide 42
Dx: PTSD
 A. The person has been exposed to a traumatic
event in which both of the following have been
present:
 (1) the person experienced, witnessed, or was
confronted with an event or events that involved
actual or threatened death or serious injury,
or a threat to the physical integrity of self or others
Slide 43
Dx: PTSD
 A. The person has been exposed to a traumatic
event in which both of the following have been
present:
 (2) the person's response involved intense fear,
helplessness, or horror.
Note: In children, this may be expressed instead
by disorganized or agitated behavior.
Slide 44
Dx: PTSD
 B. The traumatic event is persistently reexperienced
in one (or more) of the following ways:
 (1) recurrent and intrusive distressing recollections
of the event, including images, thoughts, or
perceptions. Note: In young children, repetitive
play may occur in which themes or aspects of the
trauma are expressed.
Slide 45
Dx: PTSD
B. The traumatic event is persistently
reexperienced in one (or more) of the following
ways:
 (2) recurrent distressing dreams of the event.
Note: In children, there may be frightening dreams
without recognizable content.
Slide 46
Dx: PTSD
 B. The traumatic event is persistently reexperienced
in one (or more) of the following ways:
 (3) acting or feeling as if the traumatic event were
recurring (includes a sense of reliving the
experience,
illusions, hallucinations, and dissociative flashback
episodes, including those that occur upon
awakening or when intoxicated). Note: In young
children,
trauma-specific reenactment may occur.
Slide 47
Dx: PTSD
B. The traumatic event is persistently
reexperienced in one (or more) of the following
ways:
 (4) intense psychological distress at exposure to
internal or external cues that symbolize or resemble
an aspect of the traumatic event.
 (5) physiological reactivity on exposure to internal
or external cues that symbolize or resemble an
aspect of the traumatic event.
Slide 48
Dx: PTSD
 C. Persistent avoidance of stimuli associated with
the trauma and numbing of general responsiveness
(not present before the trauma), as indicated by
three (or more) of the following:
 (1) efforts to avoid thoughts, feelings, or
conversations associated with the trauma
 (2) efforts to avoid activities, places, or people that
arouse recollections of the trauma
 (3) inability to recall an important aspect of the
trauma *****
Slide 49
Dx: PTSD
 C. Persistent avoidance of stimuli associated with
the trauma and numbing of general responsiveness
(not present before the trauma), as indicated by
three (or more) of the following:
 (4) markedly diminished interest or participation
in significant activities
 (5) feeling of detachment or estrangement
from others
Slide 50
Dx: PTSD
 C. Persistent avoidance of stimuli associated with
the trauma and numbing of general responsiveness
(not present before the trauma), as indicated by
three (or more) of the following:
 (6) restricted range of affect (e.g., unable to have
loving feelings)
 (7) sense of a foreshortened future (e.g., does not
expect to have a career, marriage, children, or
a normal life span)
Slide 51
Dx: PTSD
 D. Persistent symptoms of increased arousal (not
present
before the trauma), as indicated by two (or more) of
the following:
 (1) difficulty falling or staying asleep
 (2) irritability or outbursts of anger
 (3) difficulty concentrating
 (4) hypervigilance
 (5) exaggerated startle response
Slide 52
Dx: PTSD
E. Duration of the disturbance (symptoms in
Criteria
B, C, and D) is more than one month.
 F. The disturbance causes clinically significant
distress or impairment in social, occupational,
or other important areas of functioning.
Slide 53
Dx: PTSD
 Specify if:
 Acute: if duration of symptoms is less than 3
months
 Chronic: if duration of symptoms is 3 months or
more
 Specify if:
 With Delayed Onset: if onset of symptoms is at
least 6 months after
the stressor
Slide 54
Post-Traumatic Stress Disorder
Survivor guilt

Phobic avoidance : interpersonal
relationships; lead to marital
conflict, divorce, or loss of job.
Slide 55
Post-Traumatic Stress Disorder
The following associated constellation of symptoms
may occur and are more commonly seen in
association with an interpersonal stressor :
feelings of ineffectiveness, shame, despair, or
hopelessness; feeling permanently damaged;
a loss of previously sustained beliefs, hostility;
social withdrawal; feeling constantly threatened;
impaired relationships with others; or a change
of the individual's previous personality
characteristics.
Slide 56
Hyper and hypoactivation
 Cognitive processing regions
• Dorsolateral PFC
• Hippocampus
• Emotional processing regions
• Oribitofrontal
• Medial frontal
Slide 57
Hippocampal volume loss
 Appears consistent across number of studies
• Drug effects
• Elevated cortisol over time
• Twin study (Gilbertson et al., 2002)
Slide 58
Air Transat Flight 236
Slide 59
September 11th, 2001
Slide 60
Emotion and memory
 Emotion enhances memory and attention
(e.g., word lists, images
flashbulb memories)
Slide 61
Emotion and memory
 Alters the neural activity involved in
recollection (including AM)
Non-emotional
Emotional
Svoboda, McKinnon, Levine, submitted
Slide 62
Traumatic AM
 Traumatic AM seldom studied for real-life,
personal events
• Laboratory studies (Loftus, 1975; Christianson, 1992)
• weapons effect
• Flashbulb memory (witnessed events; Brown & Kulik,
1977;
Weaver, 1993)
Slide 63
Traumatic AM
 Personal trauma
• Alterations in memory following trauma
(in PTSD)
• Overgeneralized memory for events not
related to trauma
• similar to other disorders that involve alterations in
frontal function (depression, schizophrenia,
borderline personalitydisorder)
Slide 64
Traumatic AM
• Vulnerable to the encoding of false memories;
source monitoring
deficit (Clancy, Schacter, McNally, & Pitman,
2000)
Slide 65
Traumatic AM
 Few studies have examined memory
for trauma itself
• traumatic memories characterized as
impoverished and fragmented (van der Kolk &
Fisher, 1995;
Tromp et al., 1995)
• early childhood abuse as high as 60 % (Terr,
1991); period of
childhood amnesia
Slide 66
Traumatic AM
 Few studies have examined memory
for trauma itself
• Other studies high rate of memory accuracy,
particularly for
non-PTSD (Yuille, 1986; Schelach &
Nachson, 2001)
• differ widely in arousal, retention interval, event
characteristics
• unclear whether survey episodic or semantic AM
Slide 67
Traumatic AM
 Apparent paradox in DSM-IV-TR
where PTSD is thought to involve an:
“inability to recall an important aspect of
the trauma”
 Avoidance symptoms (suggests voluntary
control?)
 Contrasts with flashbacks (involuntary)
also described
Slide 68
Our study
AT Flight 236 passengers
PTSD versus non-PTSD
Matched controls
Slide 69
Our study
Autobiographical memory
interview
• Episodic and semantic recall
• Qualitative (e.g., perceptual versus
emotional)
• Difficult-to-retrieve memories
(Steinvorth, Levine
& Corkin, 2005)
Slide 70
Method
3 events:
• AT (Controls: highly negative
memory)
• September 11th, 2001 (witnessed;
flashbulb)
• Everyday event from same time
period
Slide 71
Int-event
Int-event
The next thing I remember is the captain coming on and confirming they
Int-event
were going to ditch. Something to the effect of they would have to make
Th/Em
an emergency landing in the ocean and I guess at that point that was
Th/Em
confirmation of the worst to come and I realized that there was no way
Int-event
we were going to survive a landing in the ocean. Taylor got worse at that
Int-event
Int-event
Th/Em
point. I prayed a lot but not too loud. I thought please don’t let us die
Th/Em
and if Taylor dies, please let me die too because I don’t think I’d survive if
Int - event
she didn’t. And I recall that there were these countdowns where the
Int-event
Int-event
captain kept saying 15 minutes to impact, 12 minutes to impact and it
Int-event
Percep
would be this wave of hysteria but then at times it just seemed quiet and
Percep
Semantic
you could hear a pin drop. Taylor was only 8 at the time.
Slide 72
Hypotheses
 AT passengers will show enhanced recollection of the
AT disaster
relative to other emotional and non-emotional events.
 Relative to passengers without PTSD, passengers with
PTSD will
show both enhanced recollection of the AT disaster and
impoverished
recollection of non-emotional autobiographical events.
 These effects will be specific to episodic (rather than
semantic)
information.
Slide 73
Results
Episodic
Mean number of details
120
100
**
80
60
40
20
0
AT psgr
Ctrl
AT psgr
Traumatic event
Ctrl
Sept 11
AT psgr
Ctrl
Neutral
Semantic
Mean number of details
10
8
*
6
4
2
0
AT psgr
Ctrl
Traumatic
AT psgr
Ctrl
Sept 11
AT psgr
Ctrl
Neutral
Figure 3. Mean number of episodic and semantic
details generated by AT passengers and controls
across three events. ** = significantly different
from controls, p < .005. * = p < .05.
Slide 74
Results
R
z = -15
z = -4
Figure 7. Amygdalar and visual cortex activation in AT passengers vs. controls (N = 2
per group) in response to viewing video recreation of the AT disaster. Between group
differences significant at t > 4.31, p < 0.05; minimum cluster size = 500 uL.
Slide 75