Download anxiety disorder

Exam: December 14, 12:00-3:00, Wood 2
• The exam is worth 25% of your final grade.
• The exam will be scored out of 75 points.
• In addition to questions associated with the lecture slides,
the exam will include questions related to chapters 7, 8, 9,
10, and 16 of the textbook. Note that chapter 11 will not
be tested on the exam.
• The exam will include 40 multiple choice questions (1
point each), 5 definitions (2 points each), and several
short answer questions (2-10 points each).
• Please bring a pencil, eraser, pen, and your student ID
to the exam.
• All electronic devices must be put away before the start
of the exam.
• All backpacks/bags should be placed at the front, back,
or sides of the examination room.
• Hats (e.g., baseball caps) should not be worn during
the exam.
Office Hours
• Prior to the exam, I will have additional office hours. If
you require assistance, please feel free to see me at
any of the following times:
Monday, December 7, 12:00-1:30.
Thursday, December 10, 9:00-10:30.
Friday, December 11, 2:30-4:30.
Outline
• Affective disorders
• Depression
• Causes
• The
monoamine
hypothesis
• Treatments
•
•
Monoamine oxidase
inhibitors
• Serotonin reuptake inhibitors
• Tricyclic antidepressants
• Other
Problems with the
monoamine hypothesis
• The diathesis stress
model
• Bipolar disorder
•
•
Treatments
• Lithium
Anxiety disorders
• Causes
• Treatments
• Hypothesis
Affective Disorders
• Affective fluctuations are felt by all of us
• What classifies it as a disorder are the
extremes that are felt and the duration.
• These extremes are so intense that
they disturb the daily functioning of the
individual affected.
• Affective disorders
Depressive episodes according to DSM
IV
• 2 weeks, at least • Severity
5:
• Mild
• Depressed mood
•
•
•
•
•
•
•
•
Few interests
Eating, weight
Sleep
Motor activity
Fatigue
Self-worth
Concentration
Thoughts of death
•
•
Moderate
Severe with/without
psychotic features
•
Partial remission
•
Full remission
•
Unspecified
• Affective disorders
Manic episodes according to DSM IV
• 1 weeks, at least
•
•
•
•
•
•
3:Grandiosity,
exaggerated selfesteem
Reduced need for
sleep
Increased
talkativeness
Flight of ideas, racing
thoughts
Psychomotor
agitation
Poor judgement
• Causes at least
1 of
•
Material distress
•
Psychotic features
•
Requires
hospitalization
•
Impairs functioning
• Severity, same
as depression
Depression
•
•
•
•
Seasonal affective disorder
Postpartum depression
Dysthymia
Bipolar disorder
Depression: Cause
• Twice as many women as men.
•
•
Menopause
Postpartum depression
• There seems to be a genetic
contributor.
•
•
Twin studies (40-50%)
Adoption studies also provide support for the role
of genetics.
• Failure to identify the locus of any
specific relevant gene.
Depression: Cause
• PET shows increased activation in the
amygdala (fear and emotion center)
and the prefrontal cortex (higher order
cognition).
• Antidepressants attenuate this increase in the
amygdala.
• However, alleviation of the depressive symptoms
through time alone does not.
Monoamine theory of
depression
• Schildkraut and Kety, 1967: hypothesized
that depression is caused by the
decreased in activity of the monoamine
transmitter synapses, namely
norepinephrine and serotonin.
• Lower concentrations of serotonin and its
metabolite (5-HIAA) in suicide attempters
who take their life.
• Variant version of the gene 5HT receptor
2A
more common in suicide victims than
Treatment:
Monoamine oxidase inhibitors
• The first kind of antidepressant to ever be used
was a monoamine oxidase inhibitor: Ipronia
• First developed to treat tuberculosis
• Ineffective for what it was intended towards; but
left patients with tuberculosis less depressed
about their disorder.
•
Monoamine agonist: increases synaptic levels of
monoamines (serotonin and norepinephrine) by
inhibiting monoamine oxidase, an enzyme that
breaks down monoamines neurotransmitters in
the cytoplasme.
Iproniazi
d
Treatment:
Selective serotonin reuptake inhibitor
• Selective serotonin reuptake
inhibitor(SSRIs)
• Fluoxetine (Prozac).
Treatments:
Tricyclic antidepressants
• Tricyclic Antidepressants
•
Names this way because their chemical structure
includes 3 rings.
• Safer alternative to MOA inhibitors
Imipramine
• Block re-uptake of both serotonin and
norepinephrine
Treatment:
Other
• Electroconvulsive therapy (ECT),
• Transcranial magnetic stimulation, and
Vagal nerve stimulation
Support for the monoamine
hypothesis
• One effective form of antidepressants
inhibit MOA (MOA inhibitors), other
increase their concentration at the synaptic
cleft (re-uptake inhibitors)
• Alleviation of depressive symptoms after
increased monoamine concentration at
synapses suggests that the affected
population lacks sufficient stimulation at
these synapses.
Problems with the monoamine
hypothesis
• Not everyone gets an alleviation of the
symptoms with the available treatments.
• Comparing the efficacy of the various
pharmacological treatments:
•
No difference in the efficacy of the different types of
treatment
•
Only 50% of people see an improvement of their
symptoms.
•
25% of control group also showed an improvement
(Placebo effect)
Diathesis stress model
• Cushing’s syndrome: characterized by high
levels of circulating glucocorticoids:
•
•
•
Consequence of pituitary tumors, producing an excess of
adrenocorticotropic hormone
Tumors of adrenal, hypersecretion of cortisol
Therapeutic treatments with synthetic glucocorticoids.
• Expression of depression occurs early.
• Role of Hypothalamic pituitary adrenal (HPA)
axis in depression?
HPA axis
STRESS!!
Hypothalamus
(CRH)
Anterior
pituitary
(ACTH)
excitatory
inhibitory
Adrenal
cortex
(Cortisol)
Diathesis-stress model
• Inherited diathesis (genetic
susceptibility) which is incapable of
initiating the onset of depression by
itself.
• The theory suggests that if the
susceptible individuals are exposed to
stress early on in life, they are then
likely to overreact to mild stressors due
to sensitization.
Diathesis-stress model
• Support for this theory comes from the
finding that patients with depression:
•
synthesize more hypothalamic Corticotropin
releasing hormone,
•
release more adrenocorticotropic hormone form
the anterior pituitary
•
and release more glucocorticoids from the
Adrenal cortex.
•
The administration of dexamethasone, a synthetic
glucocorticoid, do not reduce the release of
endogenous glucocorticoid.
•
Hospitalized depression patients and suicide
victims show high levels of cortisol.
Bipolar Disorder
• Fluctuations in mood between
depression and mania.
• The onset is earlier than unipolar
depression
• The duration and fluctuation of each
episode varies among individuals.
Bipolar Disorder
• No difference between the gender of
those affected by the disease
• Genetic analysis has shown that there
are at least genes on at least 6
chromosomes are important
• Age of onset is also heritable
• While people with family history of
bipolar disorder are at risk for
depression, the reverse is not true.
Treatments
• Antidepressant medication
• Antipsychotic medication
• Transcranial magnetic stimulation
and ECT
• Other medication (Hormones, herbs,
etc)
• Mood stabilizing medication (e.g:
Lithium)
Treatment: Lithium
• 2nd century A.D.: Seranus Ephisios recommended
the administration of water from alkaline springs to
patients suffering from mania.
• John Cade (1940s). Injected the lithium diluted in the
urine of manic patients in guinea pigs. As a control,
injected only lithium in another group of animals.
•
Both uric acid and control lithium solutions had a calming
effect on the guinea pigs
•
Because the control lithium solution had the same calming
effect, Cade concluded that the effect was due to the lithium
and not the uric acid.
Treatment: Lithium
• In the 1950’s, Morgan Schou was convinced that
lithium could be used to treat bipolar disorder
• Not only was he convinced of lithium’s ability to
prevent episodes of mania, but he also wanted to
show that lithium could prevent further
recurrence of episodes.
• With his colleague, Christian Baalstrup
performed a double-blind lithium discontinuation
study: Lithium or Placebo
• Lithium administered patients: NONE relapsed
Anxiety disorders
• Anxiety: Chronic fear that persists in the
absence of any direct threat.
• When no adaptation occurs and it
disrupts normal functioning, it is
referred to as anxiety disorder.
• Most prevalent of all psychiatric
disorders: 17% of people are effected.
Anxiety disorders
• Five classes of anxiety disorders:
•
Generalized anxiety disorder
•
Phobic anxiety disorder
•
Panic disorder
•
Obsessive compulsive disorder
•
Posttraumatic stress disorder
Anxiety disorders: Causes
• Heritability
•
A range of 30-50%
•
Higher concordance rate in identical twins than in
fraternal twins
•
However, the timing and focus of the anxiety is
shaped by the experience and the environment of
each person.
Treatment
• GABA agonists
•
Facilitation of inhibition
• Serotonin agonists
•
Does NOT work as an SSRI
•
preferred over GABA agonist
• Antidepressant drugs.
•
Comorbidity between depression and anxiety
disorder
• Cognitive behavioral therapy
Hypothesis
• Difficult to interpret results of imaging
studies: anxiety related influence on the
respiration rate. The change in the
oxygenation of cerebral blood in brain
activity can mask the effect of anxiety in
the brain.
• No structural damage found in the
amygdalas or the prefrontal cortex.
• Focus on possible role of GABA and
serotonin in anxiety disorders.
Hypothesis
• Non competitive GABA agonists alleviate
the symptoms
•
Benzodiazepine and other anxiolytics
• Functional Imaging research show that
serotonin 5HT1A receptor density
abnormality
•
Selective serotonin re-uptake inhibitors (Paxil and
Prozac), and 5HT1A receptor agonist (Buspar).
H.M.’s brain
Sliced live in San Diego
•
http://thebrainobservatory.ucsd.edu/hm_live.php
Outline
• Affective disorders
• Depression
• Causes
• The
monoamine
hypothesis
• Treatments
•
•
Monoamine oxidase
inhibitors
• Serotonin reuptake inhibitors
• Tricyclic antidepressants
• Other
Problems with the
monoamine hypothesis
• The diathesis stress
model
• Bipolar disorder
•
•
Treatments
• Lithium
Anxiety disorders
• Causes
• Treatments
• Hypothesis