Anxiety disorders and anxiolytics Flashcards
Brain circuits regulating fear
Amygdala-centred circuit
Overraction of Amygdala->OFC->ACC
Avoidance: regulated by PAG. Fight, flight, freeze
Brain circuits regulating worry
Cortico-striato-thalamo-cortical circuit
Anxious misery, apprehensive expectation, obsessions
Endocrine output of fear
increased cortisol/CAD/T2DM/stroke
Autonomic output of fear
LC
increased atherosclerosis, cardiac ischemia, BP, HRV, MI, sudden death
Met variant of COMT, implications for cognitive function
More efficient information processing in DLPFC during cognitive tasks, lower COMT, higher DA in PFC, better information processing during tasks of executive function.
However under stress, ++DA, become “worriers”
Val carriers may handle stress better, lower DA, “warriors”
Neurotransmitters that regulate “worry” in CSTC circuit
5HT, GABA, DA, NE, Glutamate, voltage-gated ion channels
Neurotransmitters associated with “fear”
Amygdala- 5HT, GABA, glutamate, CRF/HPA, NE, voltage gated ion channels
GABA receptors- which are ion, which are protein coupled
A and C are ion
Which GABA receptor do benzodiazepines bind to
GABA-> benzo sensitive. Allosteric modulatory site
Action only mediated with concurrent binding of GABA
Positive allosteric modulator
Binding of gabapentin and pregabalin
a2delta voltage sensitive calcium channel- block release of excitatory neurotransmission when neurotransmission is excessive
Bind to open, overly active VSCCs in amygdala to reduce fear, and CSTC circuits to reduce worry.
Can be useful in those that do not respond to SSRI/SNRIs due to difference mechanism, and combination in partial responders.
Proposed mechanism of anxiolytic action of buspirone
5HT1A partial agonism both at presynaptic and post-cynaptic, increasing serotonergic activity in projections to the amygdala, PFC, striatum, thalamus.
Delayed effect, likely in relation to adaptive neuronal events and receptor events
Mechanism of anxiolytic action for NRI
++NE at B1 and a1 can ++anxiety
NET/NRI likely to over time desensitise these receptors, actually reducing symptoms of fear and worry in the long term.
Mechanism of benzodiazepines to alleviate worry
GABAergic agent such as benzo’s may alleviate worry by enhancing the actions of inhibitory GABA interneurons within the PFC.
Mechanism of agents that bind a2delta of presynaptic N and P/Q voltage sensitive calcium channels
Reduce the excessive release of glutamate in CSTC circuits, therefore reducing symptoms of worry.
Mechanisms of serotonergic agents to reduce worry
PFC, striatum and thalamus receive input from serotonergic neurons, which can have an inhibitory effect on output. Thus serotonergic agents may alleviate worry by enhancing serotonin input within CSTC circuits
Process of fear conditioning
Amygdala remembers fearful events
Increasing efficiency at glutamertergic synapses in lateral aygdala as sensory input comes from thalamus or sensory cortex
Input relayed to central amygdala, where fear conditioning also improves efficiency of neurotransmission ar another glutamate synapse.
Both synapses are restructured and permanent learning is embedded into the circuit by NMDA triggering LTP and synaptic plasticity, subsequent input from sensory cortex and thalamus, very efficiently triggers fear from the amygdala.
If VMPFC unable to suppress the fear response at level of amygdala, fear conditioning.
Hippocampus remembers context of fear conditioniing and makes sure fear is triggered when fearful stimulus and all its associated stimuli are encountered
Posttraumatic stress disorder (PTSD) differs from acute
stress disorder in that
A. acute stress disorder occurs earlier than PTSD
B. PTSD is associated with at least three dissociative
symptoms
C. reexperiencing the trauma is not found in acute stress
disorder
D. avoidance of stimuli associated with the trauma is
only found in PTSD
E. PTSD lasts less than 1 month after a trauma
The answer is A
Acute stress disorder is a disorder that is similar to posttraumatic
stress disorder (PTSD), but acute stress disorder occurs earlier
than PTSD (within 4 weeks of the traumatic event) and remits
within 2 days to 1 month after a trauma (not PTSD).
PTSD shows three domains of symptoms: reexperiencing the
trauma; avoiding stimuli associated with the trauma; and experiencing
symptoms of increased autonomic arousal, such as enhanced
startle. Flashbacks, in which the individual may act and
feel as if the trauma is recurring, represent a classic form of reexperiencing.
Other forms of reexperiencing symptoms include
distressing recollections or dreams and either physiological or
psychological stress reactions on exposure to stimuli that are
linked to the trauma. Symptoms of avoidance associated with
PTSD include efforts to avoid thoughts or activities related to
trauma, anhedonia, reduced capacity to remember events related
to trauma, blunted effect, feelings of detachment or derealization,
and a sense of a foreshortened future. Symptoms of increased
arousal include insomnia, irritability, hypervigilance, and exaggerated
startle. The diagnosis of PTSD is only made when
symptoms persist for at least 1 month; the diagnosis of acute
stress disorder is made in the interim.
Acute stress disorder is characterized by reexperiencing,
avoidance, and increased arousal, similar to PTSD. Acute stress
disorder (not PTSD) is also associated with at least three dissociative
symptoms
The risk of developing anxiety disorders is enhanced by A. eating disorders B. depression C. substance abuse D. allergies E. all of the above
The answer is E (all)
Disorders that may enhance the risk for the development of anxiety
disorders include eating disorders, depression, and substance
use and abuse. In contrast, anxiety disorders have been shown
to elevate the risk of subsequent substance use disorders and
may comprise a mediator of the link between depression and the
subsequent development of substance use disorders in a clinical
sample.
Several studies have also suggested that there is an association
between anxiety disorders and allergies, high fever, immunological
diseases and infections, epilepsy, and connective
tissue diseases. Likewise, prospective studies have revealed that
the anxiety disorders may comprise risk factors for the development
of some cardiovascular and neurological diseases, such as
ischemic heart disease and migraine
Which of the following is not a sign of poor prognosis in obsessive-compulsive disorder (OCD)? A. Childhood onset B. Coexisting major depression C. Good social adjustment D. Bizarre compulsions E. Delusional beliefs
The answer is C
Agood prognosis for people with obsessive-compulsive disorder
(OCD) is indicated by good social and occupational adjustment,
the presence of a precipitating event, and an episodic nature of
symptoms. About one-third of patients with OCD have major
depressive disorder, and suicide is a risk for all patients with
OCD. A poor prognosis is indicated by yielding to (rather than
resisting) compulsions, childhood onset, bizarre compulsions,
the need for hospitalization, a coexisting major depressive disorder,
delusional beliefs, the presence of overvalued ideas (i.e.,
some acceptance of obsessions and compulsions), and the presence
of a personality disorder (especially schizotypal personality disorder). The obsessional content does not seem to be related
to the prognosis
Which of the following statements regarding anxiety and
gender differences is true?
A. Women have greater rates of almost all anxiety disorders.
B. Gender ratios are nearly equal with OCD.
C. No significant difference exists in average age of
anxiety onset.
D. Women have a twofold greater lifetime rate of agoraphobia
than men.
E. All of the above
The answer is E (all)
The results of community studies reveal that women have greater
rates of almost all of the anxiety disorders. Despite differences
in the magnitude of the rates of specific anxiety disorders across
studies, the gender ratio is strikingly similar. Women have an
approximately twofold elevation in lifetime rates of panic, generalized
anxiety disorder, agoraphobia, and simple phobia compared
with men in nearly all of the studies. The only exception
is the nearly equal gender ratio in the rates of OCD and social
phobia.
Studies of youth report similar differences in the magnitude
of anxiety disorders among girls and boys. Similar to the gender
ratio for adults, girls tend to have more of all subtypes of anxiety
disorders irrespective of the age composition of the sample.
However, it has also been reported that despite the greater rates of
anxiety in girls across all ages, there is no significant difference
between boys and girls in the average age at onset of anxiety.
Which of the following epidemiological statements is
true regarding anxiety disorders?
A. Panic disorder has the lowest heritability.
B. The mean age of onset is higher in girls.
C. The age of onset is earlier than that of mood disorders.
D. Rates in males peak in the fourth and fifth decades of
life.
E. All of the above
The answer is C
Anxiety disorders have been shown to have the earliest age of
onset of all major classes of mental and behavioral disorders
with a median onset by the age of 12 years. This is far earlier
than the onset of mood disorders or substance use disorders and
comparable to that of impulse control disorders. Women have
greater rates of anxiety disorders than men. This difference in
gender rates can be seen as early as 6 years of age. Despite the
far more rapid increase in anxiety disorders with age in girls than
in boys, there are no gender differences in the mean age at onset
of anxiety disorders (not higher in girls) or in their duration.
Female preponderance of anxiety disorders is present across all
stages of life but is most pronounced throughout early and midadulthood.
The rates of anxiety disorders in men are also rather
constant throughout adult life, but the rates in women peak in
the fourth and fifth decades of life and decrease thereafter.
Studies show a three- to fivefold increased risk of anxiety
disorders among first-degree relatives of persons with anxiety
disorders. Twin studies reveal that panic disorder has the highest
heritability and has been shown to have the strongest degree of
familial aggregation, with an almost sevenfold elevation in risk.
Sigmund Freud postulated that the defense mechanisms
necessary in phobias are
A. regression, condensation, and dissociation
B. regression, condensation, and projection
C. regression, repression, and isolation
D. repression, displacement, and avoidance
E. repression, projection, and displacement
The answer is D
Sigmund Freud viewed phobias as resulting from conflicts centered
on an unresolved childhood oedipal situation. In adults,
because the sexual drive continues to have a strong incestuous
coloring, its arousal tends to create anxiety that is characteristically
a fear of castration. The anxiety then alerts the ego to exert
repression to keep the drive away from conscious representation
and discharge. Because repression is not entirely successful in
its function, the ego must call on auxiliary defenses. In phobic
patients, the defenses, arising genetically from an earlier phobic
response during the initial childhood period of the oedipal
conflict, involves primarily the use of displacement—that is, the
sexual conflict is transposed or displaced from the person who
evoked the conflict to a seemingly unimportant, irrelevant object or situation, which has the power to elicit anxiety. The phobic object
or situation selected has a direct associative connection with
the primary source of the conflict and has thus come naturally
to symbolize it. Furthermore, the situation or object is usually
such that the patient is able to keep out of its way and by the
additional defense mechanism of avoidance to escape suffering
from serious anxiety.
Regression is an unconscious defense mechanism in which
a person undergoes a partial or total return to early patterns of
adaptation. Condensation is a mental process in which one symbol
stands for a number of components. Projection is an unconscious
defense mechanism in which persons attribute to another
person generally unconscious ideas, thoughts, feelings, and impulses
that are undesirable or unacceptable in themselves. In
psychoanalysis, isolation is a defense mechanism involving the
separation of an idea or memory from its attached feeling tone.
Dissociation is an unconscious defense mechanism involving the
segregation of any group of mental or behavioral processes from
the rest of the person’s psychic activity. Table 16.1 describes
a more current view of seven of the psychodynamic themes in
phobias
Anxiety disorders
A. are greater among people at lower socioeconomic
levels
B. are highest among those with higher levels of education
C. are lowest among homemakers
D. have shown different prevalences with regard to social
class but not ethnicity
E. all of the above
The answer is A
Community studies have consistently found that rates of anxiety
disorders in general are greater among those at lower levels
of socioeconomic status and education level. Anxiety disorders
are negatively associated with income and education levels. For
example, there is almost a twofold difference between rates of
anxiety disorders in individuals in the highest income bracket and
those in the lowest and between those who completed more than
16 years of school and those who completed less than 11 years of
school. In addition, certain anxiety disorders seem to be elevated
in specific occupations. Anxiety disorders are higher in homemakers
and those who are unemployed or have a disability. Several
community studies have also yielded greater rates of anxiety
disorders, particularly phobic disorders, among African Americans.
The reasons for ethnic and social class differences have not
yet been evaluated systematically; however, both methodological
factors and differences in exposure to stressors have been
advanced as possible explanations.
Generalized anxiety disorder
A. is least likely to coexist with another mental disorder
B. has a female-to-male ratio of 1:2
C. is a mild condition
D. has about a 50 percent chance of a recurrence after
recovery
E. has a low prevalence in primary care settings
The answer is D
Generalized anxiety disorder (GAD) is a chronic (not mild) condition,
and nearly half of patients who eventually recover experience
a later recurrence. GAD is characterized by frequent, persistentworry
and anxiety that is disproportionate to the impact of
the events or circumstances on which theworry focuses. The distinction
between GAD and normal anxiety is emphasized by the
use of the words “excessive” and “difficult to control” in the criteria
and by the specification that the symptoms cause significant
impairment or distress. The anxiety and worry are accompanied
by a number of physiological symptoms, including motor tension
(i.e., shakiness, restlessness, headache), autonomic hyperactivity
(i.e., shortness of breath, excessive sweating, palpitations),
and cognitive vigilance (i.e., irritability). The ratio of women to
men with the disorder is about 2:1 (not 1:2). The disorder usually
has its onset in late adolescence or early adulthood, although
cases are commonly seen in older adults. Also, some evidence
suggests that the prevalence is particularly high (not low) in primary
care settings. This is because patients with GAD usually
seek out a general practitioner or internist for help with a somatic
symptom. GAD is probably the disorder that most (not least) often
coexist with another mental disorder, usually social phobia,
specific phobia, panic disorder, or a depressive disorder
Physiological activity associated with PTSD include all except A. decreased parasympathetic tone B. elevated baseline heart rate C. excessive sweating D. increased circulating thyroxine E. increased blood pressure
The answer is D
According to current conceptualizations, PTSD is associated
with objective measures of physiological arousal. This includes
elevated baselines heart rate, increased blood pressure, and excessive
sweating. Furthermore, evidence from studies of baseline
cardiovascular activity revealed a positive association between
heart rate and PTSD.
The finding of elevated baseline heart rate activity is consistent
with the hypothesis of tonic sympathetic nervous system
arousal in PTSD. Disturbance in autonomic nervous system activity
in individuals with PTSD is characterized by increased
sympathetic and decreased parasympathetic tone. Preliminary
evidence suggests that this autonomic imbalance can be normalized
with selective serotonin reuptake inhibitor treatment. There
is no change in blood level of thyroxine in those with PTSD
Unexpected panic attacks are required for the diagnosis of A. generalized anxiety disorder B. panic disorder C. social phobia D. specific phobia E. all of the above
The answer is B
Unexpected panic attacks are required for the diagnosis of panic
disorder, but panic attacks can occur in several anxiety disorders.
The clinician must consider the context of the panic attack
when making a diagnosis. Panic attacks can be divided into two
types: (1) unexpected panic attacks, which are not associated
with a situational trigger, and (2) situationally bound panic attacks,
which occur immediately after exposure in a situational
trigger or in anticipation of the situational trigger. Situationally
bound panic attacks are most characteristic of social phobia and
specific phobia. In generalized anxiety disorder, the anxiety cannot
be about having a panic attack
Isolated panic attacks without functional disturbances
A. usually involves anticipatory anxiety or are phobic
B. are part of the criteria for diagnostic panic disorder
C. occur in less than 2 percent of the population
D. rarely involve avoidance
E. none of the above
Some differences between the DSM-IV-TR and earlier versions
in the diagnostic criteria of panic disorder are interesting. For example,
no longer is a specific number of panic attacks necessary in a specific period of time to meet criteria for panic disorder.
Rather, the attacks must be recurrent, and at least one attack
must be followed by at least 1 month of anticipatory anxiety or
phobic avoidance. This recognizes for the first time that although
the panic attack is obviously the seminal event for diagnosing
panic disorder, the syndrome involves a number of disturbances
that go beyond the attack itself. Isolated panic attacks without
functional disturbances are not diagnosed as panic disorder.
Furthermore, isolated panic attacks without functional disturbance
are common, occurring in approximately 15 percent of
the population.
Which of the following is not a component of the DSMIV-
TR diagnostic criteria for OCD?
A. Children need not recognize that their obsessions are
unreasonable.
B. Obsessions are acknowledged as excessive or unreasonable.
C. Obsessions or compulsions are time consuming and
take more than 1 hour a day.
D. The person recognized the obsessional thoughts as a
product of outside him- or herself.
E. The person attempts to ignore or suppress compulsive
thoughts or impulses.
d
the obsessions must be acknowledged as excessive or unreasonable
(with the exception that children need not acknowledge this fact),
there must be attempts to suppress these intrusive thoughts, and
the obsessions or compulsions are time consuming to the point of
requiring at least 1 hour a day, among other diagnostic criteria.
As part of the criteria, however, is not that the thoughts are a
product of outside the person, as in thought insertion, but that
the person recognizes that the thoughts are a product of his or
her own mind.
