Download Bill Sari Mood slides 01 - University of Illinois Archives

Mood Disorders
“I did not experience depression until I had pretty much solved my
problems. I had come to terms with my mother’s death three years
earlier, was publishing my first novel, was getting along with my family,
had emerged intact from a powerful two-year relationship, had bought a
beautiful new house, was writing well. It was when life finally was in
order that depression came slinking in and spoiled everything. I’d felt
acutely that there was no excuse for it under the circumstances,
despite perennial existential crises, the forgotten sorrows of a distant
childhood, slight wrongs done to people now dead, the truth that I am
not Tolstoy, the absence in this world of perfect love, and those
impulses of greed and uncharitableness which lie too close to the
heart- that sort of thing. But now, as I ran through this inventory, I
believed that my depression was not only a rational state but also an
incurable one. I kept redating the beginning of the depression: since
my breakup with my girlfriend, the past October; since my mother’s
death; since the beginning of her two year illness; since puberty; since
birth. Soon I couldn’t remember what pleasurable moods had been like.
I was not surprised later when I came across research showing that the
particular kind of depression I had undergone (major depression)has a
higher morbidity rate than heart disease or any cancer.”
Andrew Solomon from Anatomy of Melancholy
Diagnosis of Mood Disorders
Diagnosis of Mood Disorders requires assessment of the
patient’s present state and a setting of the present into the
context of past history. The patient may suffer from an episode
of major depression, mania, hypomania, or a mixed manicdepressive state in the present. The patient’s past history may
include episodes of these states. The patient’s past baseline
symptoms and functioning must be described, and may show
evidence of return to baseline functioning or not. Present
episodes, past episodes, and baseline symptoms/function are
put together in a time line to arrive at the specific Mood
Disorder Diagnosis. Major Depressive Disorder may be single
episode or recurrent (the most common type). Bipolar Illness
requires only 1 Manic Episode for initial diagnosis. Patients
often have past episodes of hypomania, depression and mixed
states.
Major Depressive Episode
(Note that this is not a diagnosis- it is a building block)
The core feature of a depressive episode is either depressed
mood or loss of interest or pleasure that has lasted for at least
two weeks. Patients feel depressed most of the time or have
periods when they feel better; experience markedly less
interest or pleasure in all or almost all daily activities; lose or
gain weight; have trouble sleeping or sleep too much nearly
every day; feel agitated or slowed down nearly every day; feel
fatigued; have feelings of worthlessness or excessive guilt;
note a decreased ability to concentrate or indecisiveness; and
have recurrent thoughts of death. The symptoms represent a
change in functioning, and functioning is impaired.
DSM-IV Criteria for Major Depressive
Disorder (adapted)
•Presence of an episode of Major Depression (if
only 1 episode, the disorder is classified as
Single Episode).
•The Major Depressive Episode is not better
accounted for by Schizoaffective Disorder and
not superimposed on Schizophrenia,
Schizophreniform Disorder, Delusional Disorder,
or Psychotic Disorder NOS.
•There has never been a Manic Episode, Mixed
Episode, or Hypomanic Episode.
Epidemiology of Major Depression (1)
• National Comorbidity Study
– lifetime prevalence of depressive disorders in
women is 21-24%; and men is 12-15%
– in any one year, 13% women and 8% men depressed
• From 50-70% of patients who have one episode of major
depression will have at least one subsequent episode of
depression and about 12% will have subsequent manic
episodes. Risk of relapse is greatest shortly after
remission of depressive symptoms.
• A minimum of 20 weeks of medication treatment is
considered necessary to decrease the chance of relapse.
Epidemiology of Major Depression (2)
• The longer a patient has remained well, the lower the
risk of relapse. Increased risk is associated with
chronic depression lasting two years duration and a
history of at least three previous affective episodes.
• Major depression occurs in all socioeconomic
groups and ages.
• Relatives of depressed patients (unipolar) have 2-5X
risk of major depression compared to controls. No
increase in risk of bipolar illness.
Depression Case (1)
Lauren is a 27 year old divorced white female graduate student who
came for psychiatric evaluation because, “I think there is something
wrong with me”. She had a 6 month history of problems including:
difficulty falling asleep, trouble staying asleep, early morning
awakening, a feeling of no energy, decreased concentration, crying
spells, irritability, social withdrawal, and occasional feelings of
hopeless but no thoughts of wanting to die. She felt badly about
herself, ashamed of her “weakness” . She was caught up in beliefs
that she was a failure and “not worth anyone’s time”. Things had been
going well in her Ph.D. program in Molecular Biology until a few
months ago when her inability to concentrate became severe. At that
time, she found that she could not read for more than 15 minutes, she
forgot what she read, she couldn’t concentrate on analyzing her data
without getting frustrated and giving up, and she couldn’t writesomething she had previously felt came easily to her. She began to
stay home more, which worried her friends. One of them told her that
he was worried about her as she didn’t seem “like herself”. Lauren
appreciated his concern, but was very embarrassed about seeming to
be inadequate.
Depression Case (2)
Lauren married her high school sweetheart when she was 21. She
decided to end the relationship after 5 years because of his
increasingly significant use of alcohol and total unwillingness to
address his problem. Lauren decided to start psychotherapy at age 24
when her husband’s denigration of her became severe and
emotionally painful, yet she felt “stuck”. She did not feel as bad then
as she does now, but did have notable trouble with sleep, energy level,
concentration, crying, and irritability. She believes her psychotherapy
was very helpful in allowing her to see her situation more clearly and
figure out why she had so much difficulty doing what was best for
herself. Prior to this bad period, she had 2 other times in her life when
she felt depressed, at ages 16 and 18. These periods were brief, lasting
no more than a month or two and consisted mainly of feeling sad and
tired. She described herself as, “I have always felt insecure around
other people. I don’t really think I measure up”.
Depression Case (3)
After finishing high school, Lauren attended an excellent state
university and graduated with Honors. She decided to continue on
in a graduate program because she enjoyed molecular biology and
thought a Ph.D. would give her many job options. She had three
close friends and described herself as someone who had always
valued her relationships with others. Her relationship with her
parents and 2 younger siblings was warm and supportive. Lauren
had called her parents and talked with them prior to making the
psychiatric appointment. They were interested, concerned, and
wanted to do whatever they could to help her. There were 3 family
members on her mother’s side of the family who had been
depressed, including her aunt. Her father’s father drank too much
when he was in his 20s and 30s, but stopped after he almost lost
his job. Lauren has been healthy and has no history of head injury,
seizure disorder, or toxic exposure. She has no other medical
complaints.
Mental Status Evaluation
Lauren was dressed in blue jeans and a casual shirt. She looked
tired and apprehensive, but made good eye contact with the
examiner. She sat quietly in the chair throughout the interview. Her
speech was soft and occasionally halting, but fluent. Lauren
described her mood as “down” and “blah”. Her affect was sad,
although she did not cry during the interview. She had a preserved
sense of humor. She denied having significant anxiety, except when
she worried about not being able to continue in her graduate
program. Her thinking was goal-directed, and did show negativity in
thoughts about herself. She felt like a failure and was ashamed that
she could not just “snap out of this”. There was no evidence of
hallucinations or delusions. She was oriented to person, place and
time. Her cognitive functions were intact grossly, although she
complained of having difficulty concentrating. Further cognitive
testing was not done as the patient did well in the interview. She
evidenced excellent judgement, and had some insight into her
problem, stating, “I think I am depressed, but even if this is
something else, I need to get some help.”
Questions and Discussion Points (1)
•
•
What psychiatric problem is Lauren experiencing?
• Present episode of Major Depression
• DSM-IV Diagnosis: Major depression, Mild-moderate, Recurrent.
What symptoms is Lauren experiencing?
• 6 month history of problems
• difficulty falling asleep
• trouble staying asleep
• early morning awakening
• a feeling of no energy
• decreased concentration
• crying spells, irritability
• low self-esteem and self-denigration
• shame
• social withdrawal
• occasional feelings of hopelessness but no thoughts of wanting to
die.
Questions and Discussion Points (2)
• What is Lauren’s past history?
• Past episode of depression at age 24, probably Minor
Depressive Episode, treated with psychotherapy
• Brief periods of depressive symptoms during adolescence.
• Baseline insecurity, initial poor choice of mate probably
secondary to low self-esteem and expectation of denigration
from self and others.
• Good interpersonal and work-related functioning.
• Family support.
• What is Lauren’s Family History?
• Many maternal family members with depression.
• Paternal history of alcohol dependence. (One type of family
history pattern for patients with depressive disorders is
depression in female relatives and alcohol and drug
problems in male relatives.)
Treatment
Lauren was treated with nortriptyline (a tricyclic
antidepressant- this was prior to the introduction of
fluoxetine, the first selective serotonin reuptake inhibitor)
and monthly psychotherapy. She had a full remission of
biological symptoms within 3 months on 100 mg of
nortriptyline at bedtime. Lauren was able to discuss shame,
issues of low self-esteem, and uncomfortable feelings about
her sexuality that she had been unable to talk about
previously. Therapy focused on understanding and altering
her perceptions about herself and her relationships, her
interpersonal inhibitions, and new ways of looking at herself
and relationships. She started dating within 6 months and
had a very satisfying and happy relationship for the first time
in years. At 2 years after initiation of treatment, she was
stable, free of depressive symptoms, had finished her Ph.D.,
and was engaged to be married.
Proposed Brain Mechanisms Underlying Mood
Disorders (1)
* While traumatic or stressful events can lead to symptoms of
mood disorder, this is typically treated as a separate, usually
transient “adjustment disorder with depressed mood.”
* There are theories that some (or much) depression may
arise in situations with poor social support, chronic stress,
negative personal or occupational situations, etc.
* As with schizophrenia, theories of the brain mechanisms
underlying mood disorders have been driven by the
mechanisms of action of effective drugs.
Proposed Brain Mechanisms Underlying Mood
Disorders (2)
*Post-mortem studies of subjects with major depressive disorder
(MDD) by Rajkowska and colleagues (1999, 2000) have found a
decrease in neuron density and neuronal atrophy in the
dorsolateral prefrontal cortex. This was accompanied by a
decrease in glial density.
*Imaging studies (Drevets and Raichle, 1998; Drevets, 2000) have
found decreases in cerebral blood flow and metabolism in this
cortical area in depressed patients.
*The abnormalities in blood flow and metabolism appear to be
state dependent, reversing during symptom remission (Bench et
al., 1995; Mayberg et al., 1999), and in some but not all studies
reversing with antidepressant therapy (Baxter et al., 1999;
Drevets et al., 1999).
Proposed Brain Mechanisms Underlying
Mood Disorders (3)
• Postmortem studies of brains from subjects with MDD
have also found decreases in neuronal number in the
orbital prefrontal cortex (Rajkowska et al., 1999;
Rajkowska, 2000).
• Imaging studies indicate an increase in blood flow and
cerebral metabolism in the orbital prefrontal cortex in
MDD and anxiety disorders (Baxter et al., 1987; Biver
et al., 1994; Cohen et al., 1992; Drevets et al., 1992,
1995; Ebert et al., 1991), and this is reversed with
antidepressant therapy (Drevets et al., 1992; Nobler et
al., 1994; Brody et al., 1999, Drevets 1999; Mayberg et
al., 1999).
Proposed Brain Mechanisms Underlying Mood Disorders
*One of the most common biological abnormalities in
patients with major depression is hyperactivity of the
hypothalamic-pituitary-adrenal axis, the stress response
system.
*Dexamethasone, a synthetic adrenal corticosteroid,
normally suppresses pituitary adrenocorticotropic
hormone (ACTH) release for 24 hours.
*In depressed patients this suppression is often less
pronounced or less prolonged.
*There is also evidence for elevated levels of thyrotropinreleasing hormone (TRH) and other thyroid abnormalities
in depression.
Proposed Hormonal Mechanisms
Underlying Mood Disorders
• One of the most common biological abnormalities in patients
with major depression is hyperactivity of the hypothalamicpituitary-adrenal axis, the stress response system.
• Dexamethasone, a synthetic adrenal corticosteroid, normally
suppresses pituitary adrenocorticotropic hormone (ACTH)
release for 24 hours.
• In depressed patients this suppression is often less pronounced
or less prolonged.
• There is also evidence for elevated levels of thyrotropinreleasing hormone (TRH) and other thyroid abnormalities in
depression.
Drug-based Theories of Mood Disorders I
* The initial treatments that were effective in treating
many cases of depression had in common raising the
levels of catecholamines (norepinephrine and dopamine)
at the synapse (MAO inhibitors, reuptake blockers-“tricyclic antidepressants).
* These led to the Norepinephrine and Catecholamine
(includes Dopamine) hypotheses of mood disorders.
Reduced catecholamine availability at the synapse caused
depressive disorders
* These pharmacological phenomena take effect almost
immediately, yet treatment may last 2 weeks or more
before significant symptom remission occurs.
Drug-based Theories of Mood Disorders II
* More recently, serotonin has been implicated in mood
disorders.
* Brain serotonin is low in many depressed patients and
reduced levels of the serotonin metabolic breakdown
product (5-HIAA) are common in cerebrospinal fluid.
This is common among suicidal depressives.
* Selective serotonin reuptake inhibitors (?????) are
effective in restoring mood.
Drug-based Theories of Mood Disorders II
* More recently, serotonin has been implicated in mood
disorders.
* Brain serotonin is low in many depressed patients and
reduced levels of the serotonin metabolic breakdown
product (5-HIAA) are common in cerebrospinal fluid.
This is common among suicidal depressives.
* Selective serotonin reuptake inhibitors (Prozac) are
effective in restoring mood.
* But why do SSRIs take so long to work?
Adaptive plastic change in receptors?
Questions and Discussion Points
• What kinds of medications are used in the
treatment of depression?
•Antidepressant medications.
•Mood stabilizing medications (for patients
with bipolar depression and unipolar
depression that does not fully respond to
antidepressants alone).
•Antipsychotic medications (for patients with
depression and psychosis).
Questions and Discussion Points
•
What are the features of a medication that would help with these problems?
•
•
•
•
Improve sleep architecture.
Improve mood.
Diminish anxiety
Decrease the biological component of psychological symptoms such
as low self-esteem, self-denigration, negative thinking, and shame.
• Increase available serotonin and norepinephrine
– SSRIs use reuptake inhibition
– TCAs use reuptake inhibition
– MAOIs inhibit degradation
– Mirtazepine uses 2 interesting mechanisms
» autoreceptor blockade increasing adrenergic outflow from the
presynaptic neuron
» heteroceptor antagonism (an inhibitory serotonin receptor that
resides on an adrenergic nerve terminal) leading to increased
serotonin output
Questions and Discussion Points
• What are the side effects of antidepressants?
•5-HT2 : anxiety, insomnia, sexual dysfunction
•5-HT3 (brainstem and gut): nausea, GI distress
•H1 antagonism: sedation, weight gain,
potentiation of CNS depressants
•Muscarinic (cholinergic) antagonism: dry
mouth, constipation, urinary retention, blurry
vision, tachycardia, cognitive impairment
•alpha-1-adrenergic receptor antagonism:
orthostatic hypotension, dizziness, reflex
tachycardia, impaired ejaculation, priapism.
Questions and Discussion Points
• What are some of the problems that patients face when deciding to
take medication?
• Lack of acceptance of mental disorders as diseases- the
perception that mental illness is willful and psychologically
driven. In the case of mood disorders, the states of mind
seem very “normal” the patient.
• Inability to face the illness or a desire to run away and
pretend that the illness will go away on its own.
• Lack of support from important others like family or mate.
• Realistic problems like job loss and social rejection.
• General fear of mind-altering medications (which may be
quite irrational as the individual may not fear the use of
alcohol, cigarettes, marijuana, or cocaine).
• Unhappiness with side effects of medication.
• Discomfort with the physician or other members of the
treatment team.
Questions and Discussion Points
• How can these problems be minimized?
• Education of the patient about his/her disease; the probable
course and risks if untreated, and the probable course and
benefits/risks if medication is used.
• Develop an understanding of the patient’s point of view
about his/her disease, symptoms, hopes for the future,
fears.
• Identify the patient’s strengths and help the patient mobilize
all his/her individual and social resources. Involve the
family when this is helpful.
• Acknowledge the possible risks of medication treatment
and assure the patient that he/she will be followed carefully.
• Encourage open communication between patient and
physician.
End