Ansiedad y Estres Flashcards
QUESTION ONE
A 35-year-old female presents to your office and begins to divulge
her frequent worries: ever since she was young, she was worried
someone close to her would die in a freak accident. As she grew
older, this worry was exacerbated by the fear that she would pass
away without telling her friends and family how important they are
to her. Additionally, once she had children, she became so worried
for their safety that she rarely lets them leave the house. Furthermore,
she has constant worries about how things will work out for
her in the future, and recently experienced a panic attack. Based
only on what you know here, how might you currently diagnose
this patient?
A. Posttraumatic stress disorder (PTSD)
B. Panic disorder
C. Social anxiety disorder
D. Generalized anxiety disorder
A – Incorrect. PTSD generally originates after a traumatic event; it
does not appear that this patient has ever actually experienced
a traumatic death experience. She just appears to have excessive
worry.
B – Incorrect. Panic disorder is characterized by the presence of spontaneous
panic attacks, which this patient does not report having.
C – Incorrect. Worry in social anxiety disorder is most often tied to
fear of scrutiny by others, or embarrassing oneself, in certain social
situations, whereas this patient’s worry is related to a fear of dying.
D – Correct. This patient is displaying core symptoms of generalized
anxiety disorder via generalized anxiety and worry. Although she
did have a panic attack, a single panic attack is insufficient for a
diagnosis of either panic disorder or social anxiety disorder.
QUESTION TWO
What neurocircuitry is involved in the major core symptom of
worry, which occurs across the spectrum of anxiety disorders?
A. Reciprocal connections between the amygdala and anterior
cingulate cortex (ACC)
B. Reciprocal connections between the amygdala and the periaqueductal
gray area (PAG)
C. Cortico-striato-thalamo-cortical (CSTC) loop
D. Reciprocal connections between the amygdala and orbitofrontal
cortex (OFC)
A – Incorrect. Feelings of fear, another core symptom of anxiety disorders,
are regulated by reciprocal connections between the amygdala
and the ACC. Reciprocal connections between the amygdala
and the OFC are also involved. Overactivation of these circuits
could produce feelings of fear.
B – Incorrect. Feelings of fear may be expressed through behaviors
such as avoidance, which is partly regulated by reciprocal connections
between the amygdala and the PAG. Avoidance is characterized
by a motor response and may be analogous to freezing under
threat. Other motor responses are to fight or run away (flight) in
order to survive threats from the environment.
C – Correct. Worry is regulated by a CSTC loop.
D – Incorrect. Feelings of fear are regulated by the reciprocal connections
between the amygdala and the OFC. Reciprocal connections
between the amygdala and the ACC are also involved. Overactivation
of these circuits could produce feelings of fear.
QUESTION THREE
A 46-year-old female patient has been experiencing several
anxiety-
based symptoms for many years and was previously diagnosed
with generalized anxiety disorder. She describes difficulty
concentrating in addition to difficulty falling asleep. Her family has
recently told her that she seems to be displaying heightened anger
responses toward them over minor details. Oftentimes she will cry
for extended periods of time and become irritable and distant.
Based on the above patient’s revelations, if she were to continue to
experience these stressful reactions to stimuli (i.e., excessive crying,
fatigue, problems concentrating, tension, irritability), what could
potentially occur?
A. Increased hippocampal volume
B. Reduced brain-derived neurotrophic factor (BDNF) production
C. Reduced reactivity to stress
D. Decreased hippocampal volume
E. B and D
F. A and C
A and C – Incorrect. Hippocampal volume in chronic stress is actually
theorized to decrease, not increase. Reduced reactivity to
stress may occur in patients who experience mild stressors
while growing up, which may result in an improved adaptability
when dealing with adult stressors. However, severe or
persistent stress, such as this adult is experiencing, does not
lead to reduced reactivity to stress.
B and D – Correct. Reduced BDNF production can occur in patients
who experience chronic stress, leading to a decreased ability
to create and maintain neurons and neuronal connections.
Decreased hippocampal volume, perhaps related
to decreased expression of BDNF, has been reported in
some chronic stress conditions, such as major depression,
and certain anxiety disorders. A major treatment strategy
for stress-related disorders is the use of selective serotonin
reuptake inhibitors (SSRIs), which can increase BDNF levels
because serotonin initiates signal transduction cascades
that lead to BDNF release.
E – Correct; as both B and D are correct answers.
F – Incorrect; as both A and C are incorrect answers.
QUESTION FOUR
A 51-year-old male veteran with chronic PTSD has agreed to
begin pharmacotherapy for his debilitating symptoms of arousal
and anxiety associated with his experiences in Iraq 2 years ago.
Which of the following would be appropriate as first-line treatment?
A. Paroxetine
B. Paroxetine or lorazepam
C. Paroxetine, lorazepam, or d-cycloserine
D. Paroxetine, lorazepam, d-cycloserine, or quetiapine
A – Correct. Paroxetine, a selective serotonin reuptake inhibitor
(SSRI), is approved for use in PTSD. The SSRI sertraline is also
approved for PTSD.
B – Incorrect. Lorazepam is a benzodiazepine. Benzodiazepines do not
have evidence of efficacy in PTSD and are not generally recommended
for first-line use in PTSD.
C – Incorrect. d-cycloserine, an N-methyl-d-aspartate (NMDA)
agonist, has been theorized to be useful in facilitating fear extinction,
and may be useful in conjunction with exposure therapy.
However, it is not a first-line choice.
D – Incorrect. Quetiapine, an atypical antipsychotic, is not approved as
first-line treatment for PTSD but may be useful in selected cases as
a third-line treatment, specifically for sleep and possible reduction
of nightmares.
QUESTION FIVE
A 38-year-old male combat veteran with chronic PTSD has agreed
to begin pharmacotherapy for his debilitating symptoms of arousal
and anxiety associated with his experiences in Iraq several years
ago. He is the sole survivor of his battalion in a convoy attack. He
was given the maximum doses of two different selective serotonin
reuptake inhibitors (SSRIs), approved by the US Food and Drug
Administration (FDA) for PTSD treatment, but neither alleviated
his symptoms. He has wanted to try exposure therapy, but reliving
the event is too much for him, and so he has avoided this therapy.
He may be an excellent candidate for the use of 3,4-methylenedioxymethamphetamine
(MDMA)-assisted
psychotherapy. MDMA
is a psychoactive substance that promotes release of serotonin,
norepinephrine,
and dopamine by reversing membrane-bound
transporter proteins and inhibiting reuptake in the mesolimbocortical
circuitry, and by stimulation of neurohormonal signaling of
oxytocin, cortisol, prolactin, and vasopressin. The underlying mechanism
for this type of treatment is based on:
A. Enhanced dopamine may underlie the destabilization of memory
reactivation during reconsolidation processing
B. Enhanced gamma-aminobutyric acid (GABA) may make it
easy to forget traumatic memories
C. Enhanced serotonin may allow for positive affective states and
prosocial effects that present a safe environment for reconsolidation
to occur
D. A and C
E. B and C
A – Partially correct.
B – Incorrect. MDMA is a psychoactive substance that promotes
release of serotonin, norepinephrine, and dopamine by reversing
membrane-bound transporter proteins and inhibiting reuptake in
the mesolimbocortical circuitry, and by stimulation of neurohormonal
signaling of oxytocin, cortisol, prolactin, and vasopressin. It
does not act on the GABAergic system.
C – Partially correct.
D – Correct. Dopamine signaling via ventral tegmental area (VTA)
projections to the amygdala is associated with destabilization of a
memory but is not involved in modification or restabilization of
the trace. Once a memory becomes destabilized and labile during
a therapy session, MDMA may influence activity in neurocircuitry
necessary for learning and memory. Through enhanced serotonin
release, MDMA can induce positive affective states and prosocial
effects that signal a safe and supportive setting. Prior reconsolidation
research during affective psychotherapy suggests feelings of safety
are necessary for traumatic memories to be amended with less fear.
E – Incorrect.
QUESTION SIX
A 34-year-old woman with PTSD has been treated with exposure
therapy, with partial success. Her clinician is considering an adjunct
medication. The agent d-cycloserine could be efficacious for reducing
symptoms in anxiety disorders because it has been shown to:
A. Modulate glutamate neurotransmission during fear conditioning
B. Modulate glutamate neurotransmission during fear extinction
A – Incorrect. When an individual encounters a stressful or fearful
experience, the sensory input is relayed to the amygdala, where it
is integrated with input from the ventromedial prefrontal cortex
(VMPFC) and hippocampus, so that a fear response can be either
generated or suppressed. The amygdala may “remember” stimuli
associated with that experience by increasing the efficiency of glutamate
neurotransmission, so that on future exposure to stimuli,
a fear response is more efficiently triggered. If this is not countered
by input from the VMPFC to suppress the fear response, fear
conditioning proceeds. Because d-cycloserine, as an NMDA co-agonist,
may strengthen the efficiency of glutamate neurotransmission,
it would theoretically increase rather than decrease the
likelihood
of fear conditioning.
B – Correct. Fear conditioning is not readily reversed, but it can be
inhibited through new learning. This new learning is termed fear
extinction and is the progressive reduction of the response to a
feared stimulus that is repeatedly presented without adverse consequences.
Thus, the VMPFC and hippocampus learn a new context
for the feared stimulus and send input to the amygdala to
suppress the fear response. The “memory” of the conditioned fear
is still present, however. Strengthening of synapses involved in fear
extinction could help enhance the development of fear extinction
learning in the amygdala and reduce symptoms of anxiety disorders.
Administration of the d-cycloserine while an individual is
receiving exposure therapy could increase the efficiency of glutamate
neurotransmission at synapses involved in fear extinction
QUESTION SEVEN
A 26-year-old patient with panic disorder is ready to begin
pharmacotherapy. Which of the following would be appropriate
treatment options?
A. Benzodiazepine
B. Selective serotonin reuptake inhibitor (SSRI)
C. A and B
D. Neither A nor B
A – Partially correct. For panic disorder, benzodiazepines are an appropriate
treatment option, although many clinicians prefer not to use
them as the first-line option. Benzodiazepines are also appropriate
treatment options for generalized anxiety disorder or social anxiety
disorder, although again may not be the first-line choice. They
do not have evidence of efficacy for PTSD. Most patients with
anxiety or stress-related disorders may benefit most from combined
treatment with both nonpharmacological options, such as
cognitive behavioral therapy, and pharmacological options.
B – Partially correct. SSRIs are appropriate first-line treatment options
for panic disorder as well as for generalized anxiety disorder,
social anxiety disorder, and PTSD. Most patients with anxiety or
stress-related disorders may benefit most from combined treatment
with both nonpharmacological options, such as cognitive behavioral
therapy, and pharmacological options.
C – Correct. Both benzodiazepines and SSRIs can be used to treat panic
disorder, generalized anxiety disorder, and social anxiety disorder.
D – Incorrect.
QUESTION EIGHT
A 4-year-old girl has just been removed from her home by social
services due to suspicions of abuse and neglect. Severe early life
stress can cause changes in functioning of the hypothalamic–pituitary–
adrenal (HPA) axis, which in turn can increase risk for the
development of future stress-related disorders. Research suggests
that modulation at what level may be necessary in order to prevent
the changes in HPA functioning that occur with early stress?
A. Corticotropin-releasing hormone (CRH) gene expression/CRH
activity
B. Adrenocorticotropic hormone (ACTH) gene expression/ACTH
activity
C. Cortisol gene expression/cortisol activity
A – Correct. Changes in HPA axis functioning that can occur with
severe early life stress may begin with the CRH gene. That is,
changes in CRH gene expression precede the other changes that
are seen with early mild or severe stress. Thus, in cases of mild stress,
it seems that reduced expression of CRH promotes less peptide
release in response to stress, and therefore less glucocorticoid release,
which ultimately causes upregulation of glucocorticoid receptors.
In addition, studies with non-handled rats show that blocking CRH
from binding to its type 1 receptor can lead to the same changes
and corresponding enhancements in cognitive function. Similarly,
blocking CRH1 receptors soon after exposure to early-life chronic
stress can normalize hippocampal function in adulthood.
The results of these studies suggest that some of the mechanisms
behind the risk for stress-related disorders may be set in motion at
a very young age. Accordingly, treatment may need to be administered
not after symptoms develop, but rather immediately after –
or during – exposure to early life stress, in order to prevent the
changes in gene expression that may confer greater risk later in
life. This may explain why CRH1 antagonists in major depressive
disorder in adults – long after possible exposure to early life stressors
– have been mostly ineffective.
B and C – Incorrect
QUESTION NINE
A 33-year-old female has had severe symptoms of PTSD, from an
assault that occurred 2 years ago. She still experiences flashbacks,
nightmares, and an overactive startle response when she is in a context
or situation that is similar to where she was when the assault
occurred. She may be a candidate for a more novel treatment
that combines psychotherapy and pharmacological application of
agents (e.g., beta-blockers) to disrupt reconsolidation of her fear
memories. This treatment works potentially by:
A. Reactivating the fear memories, making them labile
B. Avoiding or discounting the original fear memories
C. Using a pharmacological agent that blocks protein synthesis
associated with the original fear memories
D. Creating new memories to replace the original fear memories
E. A and C
While traumatic memories were once thought to be permanent, recent
animal experiments have shown that emotional memories can be weakened
or even erased at the time they are re-experienced. The theory of
reconsolidation proposes that by re-experiencing a traumatic memory
through psychotherapies such as exposure therapy, the memory is reactivated,
and can become a labile memory trace. In this labile state, the
original fear memory requires protein synthesis for restabilization of
the original memory. This offers a window of opportunity to target
fear memories with amnestic agents that block protein synthesis. Many
animal and human studies have demonstrated that administration of a
beta-blocker (e.g., propranolol) prior to or after memory reactivation
effectively erased the affective component from the fear memory, without
altering the actual recollection of the traumatic event.
A – Partially correct. Reactivating the memory allows it to become
destabilized, or labile. This is the first phase of the reconsolidation
treatment approach. The erasing of the affective component of the
fear memory that has been reported in reconsolidation experiments
does not occur if the original fear memory was not first
reactivated.
B – Incorrect. The purpose of this treatment approach is to reactivate
the original fear memory trace, to allow it to become labile, where
protein synthesis can be disrupted.
C – Partially correct. The second component of this treatment
approach is to combine the use of a pharmacological agent (e.g.,
beta-blocker) that has been shown to disrupt protein synthesis for memory consolidation. The noradrenergic beta-blocker propranolol
disrupts protein synthesis via the downstream beta-adrenergic
receptors/PKA/CREB signaling pathway: one of the molecular
cascades that regulate gene transcription required for the consolidation
and reconsolidation of memory. The reconsolidation disrupting
effects of propranolol were originally demonstrated in
animals and later in humans.
D – Incorrect. This treatment approach does not ignore the original
fear memory and seek to create new ones about the traumatic
event. This approach utilizes exposure to the original traumatic
memory, reactivating it and then preventing reconsolidation by
blocking protein synthesis, allowing the affective component to be
erased.
E – A and C. Correct. Reconsolidation is a two-phase process in which
retrieval of a memory initiates a transient period of destabilization,
followed by a protein-synthesis-dependent restabilization phase.
By reactivating the original memory, and disrupting protein synthesis
required for reconsolidation, the affective component can
effectively be weakened, or erased.
QUESTION TEN
Sarah is a 24-year-old patient with generalized anxiety disorder.
She is taking a benzodiazepine and has been complaining of
sleepiness associated with taking the medication. Which GABA-A
alpha subunit has been most associated with sedation properties of
benzodiazepines?
A. GABA-A receptors containing alpha-1 subunits
B. GABA-A receptors containing alpha-2 subunits
C. GABA-A receptors containing alpha-3 subunits
D. GABA-A receptors containing alpha-4 subunits
Currently available benzodiazepines are nonselective for GABA-A
receptors with different alpha subunits. Benzodiazepines bind to
GABA-A alpha subunits: alpha 1, alpha 2, alpha 3, and alpha 5. Each
of these subunits is associated with different effects, and thus benzodiazepines
not only cause sedation but are also anxiolytic, cause muscle
relaxation, and have alcohol potentiating actions.
A – Correct. Benzodiazepine-sensitive GABA-A receptors with
alpha-1 subunits may be most important for regulating sleep and
are the presumed targets of numerous sedative-hypnotic agents.
B and C – Incorrect. Benzodiazepine-sensitive GABA-A receptors
with alpha-2 subunits and alpha-3 subunits may be most
important for regulating anxiety and are the presumed targets
of anxiolytic benzodiazepines.
D – Incorrect. GABA-A receptors containing alpha-4 subunits are
benzodiazepine-insensitive, are located extrasynaptically, and regulate
tonic inhibition.
QUESTION ELEVEN
A man who was severely bitten by a dog as a child is beginning
cognitive restructuring therapy to treat his PTSD. He identifies
walking down the sidewalk past a person with their dog on a
leash as a highly distressing situation, rating his fear during such an
encounter as 80/100. He states that he strongly believes any dog is
likely to escape its leash and attack him. The next step in cognitive
restructuring would be for him to:
A. Put himself in a situation in which he encounters a dog on a
leash
B. Identify evidence for and against the thought that the dog
would escape and attack him
C. Practice techniques such as breathing exercises while thinking
about encountering a dog on a leash
A – Incorrect. Putting himself in a situation in which he encounters
his fear (i.e., a dog) would be part of exposure therapy, but is not
part of cognitive restructuring.
B – Correct. Cognitive restructuring is a process by which patients
learn to evaluate and modify inaccurate and unhelpful thoughts
(e.g., “All dogs are vicious”). There are six main steps of cognitive
restructuring: (1) identify a distressing event/thought, (2) identify
and rate (0–100) emotions related to the event/thought, (3)
identify automatic thoughts associated with the emotions, rate the
degree to which one believes them, and select one to challenge, (4)
identify evidence in support of and against the thought, (5) generate
a response to the thought using the evidence for/against (even
though <evidence>, in fact <evidence>) and rate the
degree of belief in the response, and (6) rerate emotion related to
the event/thought.</evidence></evidence>
C – Incorrect. Breathing exercises are not part of cognitive restructuring.
QUESTION TWELVE
A 39-year-old veteran presents with comorbid PTSD and substance
abuse. Her care provider recommends addressing her PTSD
and substance use disorder (SUD) simultaneously. Which of the following
statements is true regarding managing co-occurring PTSD
and SUD?
A. Individualized trauma-focused PTSD treatment, such as Prolonged
Exposure, alongside SUD intervention can reduce
PTSD severity and drug/alcohol use
B. Non-trauma-focused PTSD therapies, such as Seeking Safety,
are more effective than treatment as usual for reducing PTSD
symptoms in patients with PTSD and SUD
C. The presence of an SUD should prevent concurrent treatment
and SUD must be stabilized prior to treating the PTSD
A – Correct. Individual trauma-focused PTSD therapies that have a
primary component of exposure and/or cognitive restructuring,
such as Prolonged Exposure, when delivered together with SUD
interventions, were more likely than SUD treatment alone or
treatment as usual to improve PTSD symptoms in individuals with
co-occurring PTSD and SUD. Patients with PTSD and SUD can
tolerate and benefit from evidence-based trauma-focused PTSD
treatment such as Prolonged Exposure.
B – Incorrect. Non-trauma-focused PTSD therapies (e.g., Seeking
Safety), when delivered together with an SUD therapy, do not
improve PTSD symptoms in individuals with SUDs more than
SUD treatment alone or treatment as usual. Non-trauma-focused
therapies such as Seeking Safety for the treatment of PTSD in the
context of co-occurring SUD are not recommended.
C – Incorrect. Recent research has shown that patients with PTSD
and SUD (including nicotine use disorder) can both tolerate and
benefit from concurrent treatment for both conditions, even in the
most severe cases.
QUESTION THIRTEEN
Which of the following drugs can diminish anxiety but does NOT
have sedative, hypnotic, anticonvulsant, or musculoskeletal relaxing
activity?
A. Buspirone
B. Diazepam
C. Haloperidol
D. Mirtazapine
A – Correct. Buspirone is a serotonin 5HT1A receptor partial agonist
used to treat anxiety. Buspirone’s partial agonist actions at presynaptic
somatodendritic serotonin autoreceptors may theoretically
enhance serotonergic activity and contribute to antidepressant
actions. The partial agonist actions postsynaptically may theoretically
diminish serotonergic activity and contribute to anxiolytic
actions. It does not produce significant sedation, hypnotic, anticonvulsant,
or musculoskeletal relaxing effects.
B – Incorrect. Diazepam is a benzodiazepine that is nonspecific and
works by binding to multiple GABA-A receptor subtypes, including
the alpha-1 subunit that is important for sedation.
C – Incorrect. By blocking dopamine 2 receptors in the striatum,
haloperidol can cause motor side effects. Also, by blocking alpha 1
adrenergic receptors, it can cause dizziness, sedation, and hypotension.
D – Incorrect. Mirtazapine blocks 5HT2A, 5HT2C, and 5HT3 serotonin
receptors and blocks H1 histamine receptors. Histamine 1
receptor antagonism may explain sedative effects.
QUESTION FOURTEEN
A 38-year-old man with a history of treatment-resistant PTSD
has now experienced improvement on quetiapine 300 mg/day,
duloxetine 90 mg/day, and zolpidem 10 mg at bedtime. However,
he complains of ongoing nightmares and difficulty staying asleep.
He was previously initiated on prazosin 3 mg at bedtime, but he
experienced intolerable dizziness, and it was discontinued. Can this
patient be rechallenged with prazosin? If so, at what dose?
A. Yes; dose should be initiated at 1 mg at bedtime
B. Yes; dose should be initiated at 3 mg at bedtime
C. No; prazosin is contraindicated with quetiapine
D. No; prazosin should not be reattempted in patients with previous
intolerability
A – Correct. Prazosin, an alpha 1 antagonist, can be an effective treatment
for nightmares in PTSD. The initial dose of prazosin should
be 1 mg at bedtime and titrated up 1 mg every 2–3 days to decrease
the risk of syncope.
B – Incorrect. There is risk of “first-dose effect” syncope with sudden
loss of consciousness (1%) with an initial dose of at least 2 mg; thus,
3 mg would be too high for an initiation dose.
C – Incorrect. Prazosin is not contraindicated with quetiapine. The only
contraindications for prazosin are proven allergy to prazosin or to
quinazolines (e.g., the cancer medications gefitinib and erlotinib
or
the prostatic hyperplasia medications alfuzosin and bunazosin).
D – Incorrect. There is no reason why a patient cannot be rechallenged
with prazosin if they experienced previous intolerability (assuming
they did not have an allergic reaction). Patients may require
slower titration or lower dose if they have previously not tolerated
prazosin.
QUESTION FIFTEEN
A 28-year-old combat veteran with PTSD has not responded to
multiple trials of oral medication. He suffers from nightmares,
rarely maintains sleep longer than 2 hours, and has lost interest in
his family life, which is particularly difficult for his wife given that
she is pregnant with their first child. The role of glutamate in traumatic
memory formation and extinction suggests that ketamine
may be beneficial; however, the potential side effect profile of ketamine
could also be concerning for patients with PTSD. In a recent
controlled proof-of-concept study in PTSD, ketamine:
A. Did not reduce PTSD symptoms and caused transient worsening
of dissociative symptoms
B. Did not reduce PTSD symptoms and caused sustained worsening
of dissociative symptoms
C. Reduced PTSD symptoms and caused transient worsening of
dissociative symptoms
D. Reduced PTSD symptoms and caused sustained worsening of
dissociative symptoms
Like d-cycloserine, ketamine could theoretically strengthen the efficiency
of glutamate neurotransmission at synapses involved in fear
extinction and thus improve symptoms of PTSD. In a proof-of-concept,
double-blind, randomized, crossover trial comparing ketamine to the
active placebo control midazolam, researchers found that ketamine
infusion was associated with significant reduction in PTSD symptom
severity, assessed 24 hours after infusion. This remained significant after
adjusting for depressive symptom severity. In the study, ketamine caused
transient worsening of dissociative symptoms, but this was not sustained.
The clinical relevance of this study will be subject both to successful
replication and to identification of an alternate method of ketamine
administration. Methods that are under investigation for depression
include intranasal and intramuscular.
A – Incorrect. It is true that ketamine caused transient worsening
of dissociative symptoms; however, it also reduced PTSD
symptoms.
B – Incorrect. Ketamine caused transient but not sustained worsening
of dissociative symptoms.
C – Correct. Ketamine reduced PTSD symptoms and caused transient
worsening of dissociative symptoms.
D – Incorrect. Ketamine reduced PTSD symptoms but did not cause
sustained worsening of dissociative symptoms.
