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Panic Disorder Biology
Prof. Hani Hamed DDeessssookkii,, MM..DD..PPssyycchhiiaattrryy
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• Panic has not always been recognized as
an exclusively psychiatric condition.
Research in this area continued along
separate medical and psychological axes
until 1980, when the development of
Diagnostic and Statistical Manual (DSM)-
III criteria established the overall concept
of panic disorder.
• The history of the word panic, of the concepts of Panic
attack and of Panic Disorder is a complex one.
• The adjective word panic, derived from the Greek,
stressed initially the intensity of a feeling of unjustified,
individual or collective, fear.
• In their present meanings, the concepts belong to the
group of anxiety states, the Panic attack being a
symptom characterized by a paroxysmal anxiety which
may appear in various psychopathological states,
whereas the Panic Disorder is a nosological category
whose diagnostic criterium is the appearance, with a
definite frequency, of Panic attacks.
• The disorder is frequently associated to agoraphobia
considered, when it exists, as a complication.
Panic Attacks & Panic Disorder
• It is common to confuse panic attacks with panic disorder.
• To qualify for the diagnosis of panic disorder itself, patients
must have some panic attacks that are entirely
• Panic attacks can also be reproducibly triggered by certain
specific situations for various individuals & therefore can
• Situations that frequently act as triggers for panic attacks
e.g. driving or riding in a vehicle, esp over bridges,
shopping in crowded stores.
• The perception of lack of control or feeling "trapped" is a
common theme in situational triggers.
• Panic disorder affects up to 2 % of the population,
but < 1/3 receive treatment.
• It typically begins in late adolescence or early
adulthood but can present in childhood.
• Onset is rare after age 45.
• It is more prevalent in women (2:1).
• Genetic studies demonstrate a 15 to 20% rate of
panic disorder in relatives of patients with panic
disorder, including a 40% concordance rate for
panic disorder in monozygotic twins.
Panic Attack Facts
• Panic attacks can occur at any time, even during sleep.
• An attack usually peaks within 10 minutes, but some symptoms may
last much longer.
• Panic disorder affects about 6 million American adults
• Panic disorder is twice as common in women as men.
• Panic attacks often begin in late adolescence or early adulthood,
• Not everyone who experiences panic attacks will develop panic
disorder. Many people have just one attack and never have another.
• The tendency to develop panic attacks appears to be inherited.
• Panic disorder is often accompanied by other serious problems, such
as depression, drug abuse, or alcoholism.
Comer, Fundamentals of Abnormal Psychology, 3e 9
This chapter no longer includes OCD and
DSM 5 creates new chapters for OCD and
Panic Attacks and Agoraphobia are “unlinked”
in DSM- 5
DSM- IV terminology describing different
types of panic attacks replaced in DSM-5 with
the terms “expected” or “unexpected” panic
• Although not generally recognized, panic
disorder patients have a suicide rate
comparable with that of patients with MD.
• 20 to 40% of panic disorder patients report
having made suicide attempts & about 1/2
admit to having had suicidal ideation.
• This high rate of suicide attempts does not
appear to be caused by the presence of
The Biological Perspective
• It is also unclear why some people have
such abnormalities in norepinephrine
– Inherited biological predisposition is one
• Prevalence should be (and is) greater among close
– Among monozygotic (MZ, or identical) twins = 24%
– Among dizygotic (DZ, or fraternal) twins = 11%
• Issue is still open to debate
1. Brain stem: fires off systemically to create autonomic symptoms
2. Amygdala and Limbic System: generates anticipatory anxiety
3. Pre-frontal cortex: generates phobic avoidance
Neurotransmitter : dysregulation
• The theory of initial excess of NE is
supported by evidence that panic disorder
patients are hypersensitive to alpha-2
antagonists & hyposensitive to alpha-2
• Thus, yohimbine, an alpha-2 antagonist,
acts as a promoter of NE release by
"cutting the brake cable" of the
presynaptic NE autoreceptor → an
exaggerated response in panic disorder
patients, including the precipitation of
overt panic attacks.
• Caffeine is also panicogenic (4-6 cups of coffee →
• It is an adenosine antagonist & can be synergistic
• On the other hand, panic patients have a blunted
physiological response to postsynaptic adrenergic
agonists, perhaps as a consequence of an
overactive noradrenergic system.
• Thus, there may be a dysregulation in the
noradrenergic system, with changes in the
sensitivity of noradrenergic neurons & their
receptors altering their physiological functioning.
• GABA & its allosteric modulation by bz have also
been implicated in the biological basis of panic
disorder i.e. the ability of bz to modulate GABA is
out of balance.
• This may be due to changes in the amounts of
endogenous bz (i.e., "the brain's Xanax"), or to
alterations in the sensitivity of the bz receptor itself.
• Alternatively, it is possible that the brain is
producing an excess in anxiogenic inverse
agonists, causing the panic disorder patient to
have more anxiety & panic attacks.
• Some data suggest an abnormality in the bz receptor in
which the "set point" is shifted toward the inverse agonist
• Thus, Cl channel conductance is already too diminished.
• Evidence comes from the fact that such patients require
administration of exogenous bz ligands (i.e. Xanax) to reset
the receptor complex's set point back to normal.
• Also, flumazenil, which is neutral & without behavioral
effects in normal subjects because it acts as a relatively
pure antagonist, can act differently in panic disorder
• It acts as an inverse agonist, perhaps via an abnormal shift
of the set point to the right, toward an inverse agonist
conformation → provokes panic attacks.
Intrinsic Activity at D2 Receptors
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مقلدات كاملة هذه المقلدات تنشط الخلية وتعطي full agonist
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