Anxiety disorder collection

psychiatry in internal medicine

1. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
SOCIAL ANXIETY DISORDER
Introduction
Epidemiology
Prevalence
●Canadian community survey- 15% have of fear in social situations like giving a
speech in public
●National comorbidity survey- replication (NCS-R)
o12 month prevalence - 6.8% (generalized
oLife time prevalence - 12.1%
●Common among Female, single and low SES in epidemiological studies. In
clinical population equally distributed among males ad females.
●Earlier age at onset and chronic course

Clinical features
●Age at onset –
●onset of SP is typically during childhood and adolescence, and that onsets later in
life, after this peak period for onset, are relatively rare and usually confined to
cases of SP occurring secondarily to or as part of another mental disorder like
depression, eating disorder
●Centered around scrutiny by other people in comparatively small groups as
opposed to crowds usually leading to avoidance of social situation
●Associated with low self esteem and fear of criticism
●The usual symptoms are blushing, hand tremor, nausea, urgency of micturition,
may progress to panic attack
●A fear of vomiting in public may be important
●Direct eye to eye confrontation may be stressful
●May avoid eating, drinking or writing in public with the fear of being embarrassed
●Adults recognize that the fear is excessive or unreasonable
●Anticipatory anxiety is common

Subtypes​ – Generalized and non generalized/ circumscribed
Generalized –
●Anxiety / avoidance in most social situations
●More comorbidity, greater impairment, low QOL
Circumscribed – Circumscribed social situations
Distinctions between the subtypes
●Circumscribed subtype exhibited greater cardiac reactivity than generalized
●Generalized type is more frequently associated with history of childhood shyness
indicating a larger genetic component
●Circumscribed type is more commonly associated with traumatic condition
●Response to CBT – better with circumscribed type
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

2. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
●However epidemiological findings support a quantitative relationship than
qualitative. Latent class analysis of NCS data showed 3 groups spanning across a
quantitative continuum. Other community surveys also report that number od
social fears could not be used to establish a defensible subtyping system.
Although categorical distinctions may be used, the data supports a continuum
model of severity.
Social phobia and AAPD
●Comorbidity ranges from 20 to 80%
●Studies suggest that generalized social phobia with or without AAPD doesn’t
differ on subjective reports of distress, heart rate, speech length, negative thoughts
during behavioral tasks, cognitive interference tasks.
●Similar rates of these two disorders in relatives of social phobia probands and
absence of AAPD in any relative of control probands.
●AAPD is not a significant factor in treatment outcome
●Current findings suggest that social phobia and AAPD are quantitatively related
with latter as the severe form.
Cultural factors in phenomenology-
Taijin-kyofu-sho (TKS) is seen in oriental countries. TKS involves the fear of offending
others by embarrassing them or by making uncomfortable through a personal flaw or
shortcoming like emitting a bad odor, blushing in front of others, exposing an unsightly
body part. TKS is a cultural pattern of social anxiety because it reflects the
“other-oriented” nature of eastern societies, just as social phobia reflects “self-oriented”
nature of western societies.

Nosology
DSM-IV
●A marked and persistent fear of one or more social or performance situations
involving exposure to unfamiliar people or possible scrutiny by others.
●The person fears that he or she will act in a way (or show symptoms of anxiety)
that will be humiliating or embarrassing.
●Exposure to the feared social situation almost invariably provokes anxiety, which
may take the form of a panic attack.†
●The person recognizes that the fear is excessive or unreasonable.†
●The feared social or performance situations are avoided or endured with intense
anxiety or distress.
ICD -10
All of the following criteria should be fulfilled for a definite diagnosis
1.Physiological, behavioral and autonomic symptoms must be primarily
manifestations of anxiety and not secondary to other symptoms such as delusions
or obsessional thoughts
2.Anxiety must be restricted to or predominate in particular social situations
3.The phobic situation is avoided whenever possible
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

3. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin

Differential diagnosis
Agoraphobia​ – May contribute to sufferers becoming housebound. If the distinction
between social phobia and agoraphobia is very difficult, then precedence should be given
to agoraphobia.
Depression​- may also make a person to become housebound. Depressive symptoms are
common and a diagnosis of depressive disorder is not made until a full depressive
syndrome can be identified
PDD or schizoid personality
Lack of interest in relating to others, than anxiety
GAD
The fear of scrutiny may be present along with anxiety, but this is not the primary focus
Comorbidity
1.Depression – seen in 70%
2.Other anxiety disorder - agoraphobia 36%, GAD 33%, simple phobia 20%, OCD
16%, PTSD 11%, panic disorder without agoraphobia 9%
3.Substance use disorder – seen in 40%
4.BPAD
a.In STEP-BD SAD was the most common comorbid anxiety disorder with
12.7% current prevalence and 22% life time prevalence
b.Presence of SAD associated with earlier onset of BPAD and poor
prognosis
5.Eating disorder
a.Price foundation collaborative genetic study of eating disorder- Presence
of social phobia in 20%
b.Co aggregation in families seen
6.Personality disorder - Harvard-brown anxiety research program and NCS data
a.61% of social phobia have axis II
b.30% AAPD – lower likelihood of remission
c.Improvement in one disorder was correlated with another with respect to
AAPD and SAD
Etiopathogenesis
Neurobiology
Neuroimaging
1.Decreased activity of right parietal, right temporal and insular cortex in response t
a stressful task such as simulated public speaking
2.Elevated regional blood flow in right prefrontal, left inferior temporal cortex and
left amygdaloid hippocampal region on PET scan
3.Exaggerated dorsal anterior cingulate cortex activity in response to disgust faces.
Increased amygdalar activation towards neutral faces has been noted on fMRI.
Greater reactivity in left allocortical (amygdale, uncus and parahippocampal
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

4. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
gyrus) areas in response harsh faces as compared to happy faces when compared
to controls.
4.Lower striatal dopamine reuptake site density and decreased D2 receptor binding.
Social phobia prevalence is higher in patients with parkinsonism.
Genetics
Family and twin studies
●Heritability is 30% (Virginia twin study by Kendler)
●In family members increased risk 16% compared to controls 5%
●Incidence of generalized social phobia is around 25% in relatives of probands
with social phobia compared to control probands <5%
No adoption studies
Serotonin transporter gene
Two types of serotonin transporter gene are present- S (short) or L (long) allele on
chromosome 17. Presence of 1 or 2 copies of S allele predisposes to the development of
anxiety, avoidant behaviors and negative affect. S allele confers reduced transcription
that is 50% decreased serotonin uptake.
●Amygdalar response to angry or fear faces was increased in carriers of S allele. S
carriers have greater coupling between amygdale and ventromedial prefrontal
cortex.
●S allele was associated with enhanced amygdalar excitability in response to a
public speaking stressor task on PET scan.
●S allele is associated with shyness in children and predicted smaller N-400
response to anger and neutral face.
COMT
A functional polymorphism in the gene substitution of methylene (​met ​) for valine (​val ​)
results in COMT with decreased activity. Those having ​val ​ allele have increased activity
of COMT there by increasing g prefrontal dopamine catabolism and is associated with
increased risk of phobic anxiety.
Peripheral markers
●Density of peripheral BZD receptor density in platelets was decreased.
●No evidence of peripheral abnormalities of lymphocyte beta adrenergic receptor
density, platelet serotonin receptor capacity, G protein subunit levels.
Chemical challenges ​ - ​none of the symptoms provoked are similar to patient’s typical Sx.
●Epinephrine fails to induce social phobia symptoms
●Lactate doesn’t induce panic attacks
●Pentagastrin induced panic attacks are different from the patient’s typical anxiety
symptoms
●35% CO2 induced panic attacks


Psychological theories
Behavioral inhibition model
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

5. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
A stable temperament recognizable in early childhood, where in children behave in a
timid, fearful manner when exposed to novel environment. They have increased latency
to speak, decreased exploratory behavior, increased heart rate, elevated cortisol and
catecholamine levels. Behavioral inhibition can lead to decreased social interaction
and/or uncomfortable social interactions, which may lead to social fears and social
anxiety which in turn leads to social phobia.
Cognitive model
Dysfunctional assumptions by individual with social phobia are
1.He will behave in an inept, incompetent or humiliating fashion
2.As a result of behavior performance there will be a disastrous or catastrophic
consequence.
Ethological model – Ohmanor
This model posits an evolutionary wariness of being stared at, which in some individual
lead to arousal and alarm. This sensitivity to eye contact scrutiny is a trait that is
inherited.
Conditioning model
A conditioned aversive stimulus can lead to the development of social phobia. Few report
a traumatic incident that led to the development of phobia.
Personality model
Shyness is a personality trait that is genetically determined and leads to discomfort in
particular social situations, which can lead to worry about situation and arousal or
avoidance of them.


Assessment
1.Liebowitzz Social Anxiety Scale (LSAS)
2.Social avoidance and distress scale
3.

Treatment
Pharmacological
FDA approval – paroxetine, sertraline, venlafaxine,
Studies are also available for fluoxetine, fluvoxamine, escitalopram
Drugs used
First line agent – SSRI, SNRI
Second line agents - MAO- I, BZD, Ca channel blockers

SSRI
Best evidence for Paroxetine and sertraline
Evidence also present for fluoxetine, fluvoxamine, escitalopram
Relative risk of non response is 0.67 (Cochrane review)
Better than RIMA , no head to head trial with phenelzine
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

6. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
MAO I
Phenelzine ​ proven in multiple studies to be effective
Considered reference medication in treatment efficacy for social phobia
Because of its side effects is not the medication of choice
Moclobenide ​ safe compared to phenelzine, but not as efficacious
Brofaromine ​ is not manufactured now, but was considered to be more efficacious
Benzodiazepines
Alternative to SSRI
Evidence for clonazepam
Rapid onset of action
SNRI- ​venlafaxine
Effect has been proven in multiple double blind studies
Has same effect at both lower dose -75 mg and higher doses- 225mg
Alpha2 calcium channel blockers​ – Gabapentin and pregabalin
Both are proven efficacious in DBPRCT
Others
1.Olanzapine
2.Levitriacetam
3.Botulinum toxin – for axillary hyperhydrosis associated with SAD. Administered
intradermal.
4.Propranolol – for performance anxiety. 1 hour before the performance
Relapse prevention
Data present for Paroxetine, sertraline and escitalopram. <15% had relapse compared to
>35% on placebo

Psychosocial


Harvard/brown Anxiety Research project- ​A longitudinal study conducted in US,
studying various measures of anxiety disorders mainly social anxiety disorder, panic
disorder, generalized anxiety disorder.
Methods
Subjects are referred from private and government set up with a diagnosis of 1 or 2
anxiety disorder. Using structured assessment they were assessed at baseline and again
once in 6 months or one year duration for a minimum of 13 years. A total of 711 subjects
were recruited in 1989.
Results pertaining to SAD
●Most common diagnosis was panic disorder with agoraphobia 50% and without
agoraphobia 12%, depression 27%, SAD 25%, GAD 25%.
●Comorbid conditions (in %)– panic disorder with agoraphobia 36, GAD 33,
simple phobia 20, OCD 16, PTSD 11, panic disorder without agoraphobia 9.
Major depression in 35% and dysthymia in 23% was also seen
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

7. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
●Comorbid personality disorder was seen in 44 % with AAPD being the
commonest 36% followed by borderline 8%, OCPD 7%
●Remission rate was lowest for SAD – 35% and lowest relapses were also seen
with SAD – 34%
●Diagnostic stability – for around 50% of patients during the course of follow up
the predominant anxiety disorder was different from the index episode that is
SAD
●Non pharmacological treatment utilization declined over the course of the follow
up mainly due to lack of efficacy but pharmacological treatment utilizers
remained the same
Implications
●SAD is a chronic condition with more or less a continuous course
●Has significant comorbidity
●As it is a chronic condition needs pharmacological treatment for prolonged
duration


Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

8. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
SPECIFIC PHOBIA
Introduction
It is a relatively common psychiatric disorder across the population
Objects that become the target of phobia are those that cause distress and distaste in the
general population
Relatively few individuals present for treatment because they view the fear as normal part
of their personality or many stimuli can be avoided without much difficulty.
Epidemiology
Age at onset
●Mean age at onset is 13-16 years
●Persons with situational phobia have a later age (ex: claustrophobia 20 years) at
onset than with other types
●Animal and blood- injection phobia begin in childhood (7-9 years mean age at
onset)
●Many specific fears in youth are relatively transient but those that extend into
adulthood are more severe and persistent.
Prevalence​ – 8.8-12.5%
Sex-
●Women:men – 2:1
●Women – higher rates of multiple phobias
●Blood injury phobia is an exception in that sex ratio is equal

Clinical features
●The individual experiences a marked, persistent and excessive or unreasonable
fear when in the presence of or when anticipating an encounter with a specific
object or situation and when not confronted with the stimulus, individual is
generally symptom free.
●The focus of the fear may be
oAnticipated harm from some aspect of the object or situation
oConcerns about losing control, panicking, somatic manifestations of
anxiety and fear
●Anxiety is invariably felt when immediately on confronting the stimulus and the
level of anxiety increases with proximity of stimulus and the chances of escape
from the stimulus is not possible
●Individual should recognize that the fear is excessive and unreasonable
●If the phobia does not significantly interfere with the individual’s functioning or
cause marked distress the diagnosis is not made
●Fears of magic or spirit should be diagnosed as phobia only if it is considered as
excessive in the cultural context
●In children anxiety may be expressed as crying, tantrums, freezing or clinging.
Children do not recognize fear as excessive or unreasonable. Fear of animals or
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

9. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
natural circumstances is a transient feature in childhood and should be diagnosed
as phobia only if it is causing clinically significant impairment
●All phobic individuals will show 2 broad sets of symptoms
oFirst id the anxiety or sympathetic nervous system activation that occurs
on anticipation of or confrontation of stimulus
oSecond is the desired or attempted avoidance that individual engage in.
●But in some individuals with blood-injury type the response can be different. It is
characterized by fainting, due to vasovagal response. It is characterized by initial
brief acceleration of heart rate and elevation of blood pressure followed by a
deceleration of heart rate and a drop in the blood pressure.
Subtypes
1.Animal type
2.Natural environment type – warter, storm
3.Blood injection injury type – highly familial
4.Situational type – has a bimodal onset distribution, with one peak in childhood
and another in the mid 20s. Appears similar to panic disorder with agoraphobia in
sex ratio, age at onset, familial pattern.
5.Other type
They can also be classified on the basis of principle emotion they elicit, like (Davey)
1.Disgust
2.Fear
Course
Usually starts in childhood or adolescence and occur at younger age for women than men
Phobias of traumatic origin can arise at any age
Specific phobias in adolescence increases the chances of either persistence of specific
phobia or development of additional phobias in adulthood
Phobias that persist into adulthood remit infrequently (only 20% cases remit)

Nosology
ICD-10
All of the following should be fulfilled for a definite diagnosis
1.Psychological or autonomic symptoms must be primary manifestations of anxiety
and not secondary to other symptoms such as delusion or obsessional thought
2.Anxiety must be restricted to the presence of particular phobic object or situation
3.Phobic situation is avoided whenever possible
DSM-IV
1.Marked or persistent fear that is excessive or unreasonable, cued by the presence
of or anticipation of a specific object or situation
2.Exposure to the phobic stimulus almost invariably provokes an immediate anxiety
response, which may take the form of a situationally bound or situationally
predisposed panic attack
3.Person recognizes that the fear is excessive r unreasonable
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

10. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
4.Phobic situations are avoided or else is endured with intense anxiety or distress
5.In individuals under age 18 years the duration is at least 6 months
6.The symptoms interferes with the person’s normal routine or relationships or
there is marked distress about having a phobia

Differential diagnosis
1.Hypochondriacal disorder- fears of specific diseases unless they relate to specific
situations. Dysmorphophobia is included in hypochondriacal disorder or
delusional disorder depending on the conviction in ICD. In DSM they are
classified as having body dysmorphic disorder.
2.Delusional disorder - If the conviction of the disease reaches delusional intensity.
3.PTSD – the intrusions and nightmares are not present in phobia and the fear is
triggered by an external event
4.Panic disorder – Fear is specifically focused on having a panic attack. DSM
recommends that info about the following will be helpful to differentiate
a.Situations that elicit the fear
b.Type and number of panic attack
c.Range of situations that the individual avoids
d.Level of anxiety between episodes of fear

Comorbidity
1.Other phobias – agoraphobia, social phobia
2.Affective disorder
3.Other anxiety disorders

Etiopathogenesis
Neurobiology
●Genetics ​ – Family studies have shown higher risk for specific phobia among 1​
st

degree relatives of probands, more specific for blood-injury phobia. Kendler
determined that the familial aggregation of phobia is accounted by genetic factors
to 30% in a twin study.
●Neuroimaging ​ – Associaton between paralimbic structures and anxiety state
experienced but inconsistent
●No change compared to controls on CO2 test
Neuronal circuits- Fear response to conditioned stimuli is mediated by amygdala without
hippocampal memory or cortical based knowledge of why there is fear.

Psychological theories
Direct conditioning
1.Little albert study – Watson and Raynor reported that the pairing of white rat with
a loud noise produced a conditioned fear response when the participant was
exposed to rat in future occasions
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

11. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
2.Mowrer extended the theory of classical conditioning by proposing that
conditioning is mediated by motivations such as desire to reduce fear
3.Drawbacks of conditioning model are,
a.distinct categories of fears noted in epidemiological studies are in contrary
to the conditioning theory that any stimuli can become a feared stimulus
b.A traumatic etiology is not reported by most individuals
c.Limited success of studies to condition stable fears in humans in
experimental setting
d.Many people experience aversive conditioning but do not develop a
phobia
Preparedness and Vicarious conditioning
●Seligman developed preparedness theory of fear acquisition
●Stimuli that become the target of phobia are biologically threatening
●Certain stimuli are evolutionarily prepared to support phobic response
●According to this theory phobic thought is,
1.Acquired through one trial conditioning
2.Non-cognitive
3.Object will involve a threat relevant to humankind
4.Not easily extinguished
●Vicarious learning relies on the fact that learning occurs through observation
●A small subgroup of individuals with phobia nominate vicarious pathways as the
perceived mode of onset

Verbal acquisition
●Seen in epidemics of “koro”- a disorder seen in Singapore and eastern countries in
which the person percieve that his genitals are shrinking and intense fear of dying.
The epidemics were thought to have been caused by verbal transmission via
media
●In experimental conditions, if the participant is informed that the stimulus would
be followed by a shock then there is increase in the skin conductance to target
stimulus

Non-associative means
●Phobias may be acquired without previous direct or indirect associative learning
●Only 1 percent of phobic individuals recall a classical conditioning episode
●Visual cliff apparatus test – all infants crawled on to the safe side of the cliff
●Natural selection has prepared humans with the ability to avoid, without prior
experience, situations that could lead to significant harm

Mediation by cognitive factors
Focus of attention is on
1.Interpretation of physiological changes that accompany anxiety
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

12. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
2.Anticipatory plans to avoid the feared stimulus
3.Thoughts relating to escape from the stimulus
Dysfunctional beliefs
●When ever the individual is exposed to phobic stimulus, negative self statements
are triggered which heighten the physiological activity and the cycle continues
Biases in information processing
●Attentional bias toward phobia related threats – as seen in emotional stroop test
and dichotic listening task.
●Both self efficacy and exaggerated perception of danger are additional cognitive
factors that are likely to mediate phobic reactions
Psychodynamic theory ​ – “case of little Hans”, where the boy had phobia towards horses.
Freud postulated that Little Hans had unconscious and sexual feelings towards the mother
and aggressive, rivalrous feelings for his father. This feeling was blocked by repression
and then displaced to a symbolic object, in this case horses, the avoidance of which partly
relieved little Hans’s anxiety

Assessment



Treatment
Pharmacoogical
Medications have not been shown to be effective.
Only few trials – SSRIs are effective, mainly Paroxetine.
TCA,BZD, Beta blockers are not effective.

Psychosocial
Exposure therapy
1.Flooding – ​ Patient is exposed to the phobic stimulus and is made to remain there
till the anxiety is dissipated.
2.In vivo exposure – ​live exposure to the phobic object in graded fashion, beginning
with situations that elicit minimum anxiety and moving along the hierarchy
3.Modeling – ​The therapist encourages to have contact with the phobic object by
demonstrating to the patient
4.Systematic desensitization – ​Relies on progressive muscle relaxation to manage
the anxiety elicited during imaginal exposure to phobic stimulus. Anxiety
provoking images are imagined while maintaining an incongruent relaxed state.
Intensive single session is as successful with a group, as when individual therapy is
conducted.

Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

13. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Eye movement desensitization and reprocessing – ​ ​Same as systematic desensitization
except that during relaxation horizontal eye movements are elicited from patient by hand
movements of therapist.
Hypnotherapy – ​ ​No​ ​RCTs. Only case reports.

Applied tension -
For blood injection phobia, with fainting as main feature where exposure alone may not
be feasible. Involves instructing the patient to rapidly and frequently tense various muscle
groups during exposure, an activity that creates a physiological state that is incompatible
with fainting.






Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

14. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Phobias beginning with the letter A
Acarophobia Itching
Achluophobia Darkness
Acousticophobia Noise
Acrophobia Heights
Aerophobia Drafts
Agliophobia Pain
Agoraphobia Crowds
Agraphobia Sexual abuse
Agrizoophobia Wild animals
Aichmophobia Needles, pointed objects
Ailurophobia Cats
Alektorophobia Chickens
Algophobia Pain
Altophobia Heights
Amathophobia Dust
Ambulophobia Walking
Ancraophobia Wind
Androphobia Men
Anthrophobia Flowers
Aphenphosmphobia Being touched
Apiphobia Bees
Apotemnophobia Amputees
Arachibutyrophobia Peanut butter sticking to the roof of the mouth
Arachnophobia Spiders
Asthenophobia Fainting, weakness
Astraphobia Thunder and lightning
Aviatophobia Flying
B Phobias
Barophobia Gravity
Bathophobia Depth
Batonophobia Plants
Bibliophobia Books
Bromidrophobia Body odours
Brontophobia Thunder and lightning
Bufonophobia Toads
Phobia names beginning with C
Carnophobia Meat
Catoptrophobia Mirrors
Ceraunophobia Thunder
Chaetophobia Hair
Cheimatophobia Cold
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

15. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Chionophobia Snow
Cibophobia Food
Cleptophobia Stealing
Coimetrophobia Cemeteries
Coitophobia Coitus
Coprophobia Feces
Coulrophobia Clowns
Cremnophobia Precipices
Cryophobia Extreme cold

Phobias starting with D associated with fear
Demophobia Crowds
Dendrophobia Trees
Dentophobia Dentists
Dermatopathophobia Skin disease
Dermatophobia Skin lesions
Didaskaleinophobia School
Dinophobia Dizziness
Diplophobia Double vision
Dipsophobia Drinking
Dutchphobia The Dutch
Dysmorphophobia Deformity

E
Ecclesiophobia Church
Ecophobia Home
Eisoptrophobia Mirrors
Electrophobia Electricity
Elurophobia Cats
Emetophobia Vomiting
Enetophobia Pins
Entomophobia Insects
Epistaxiophobia Nosebleeds
Epistemophobia Knowledge
Equinophobia Horses
Ergophobia Work

F
Felinophobia Cats
Francophobia France
Frigophobia Cold

Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

16. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
G
Galiophobia France
Gamophobia Marriage
Genophobia Sex
Genuphobia Knees
Gephyrophobia Crossing bridges
Gerascophobia Growing old
Germanophobia Germany
German culture
Glossophobia Speaking in public
Gymnophobia Nudity
Gynophobia Women

H
Hadephobia Hell
Hagiophobia Holy things
Heliophobia The Sun
Hemophobia blood
Herpetophobia Reptiles
Heterophobia The opposite sex
Hierophobia Priests
Hippophobia Horses
Hominophobia Men
Hydrophobia Water
Hydrophobophobia Rabies
Hypegiaphobia Responsibility
Hypertrichophobia Hair
Hypnophobia Sleep

I
Iatrophobia Going to the doctor
Ichthyophobia Fish
Illyngophobia Vertigo

J
Japanophobia Japanese
Judeophobia Jews

K
Kakorrhaphiophobia Defeat
Katagelophobia Ridicule
Kathisophobia Sitting down
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

17. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Kenophobia Empty spaces
Kolpophobia Genitals
Koniophobia Dust
Kopophobia Fatigue

L
Lachanophobia Vegetables
Laliophobia Speaking
Ligyrophobia Loud noises
Lilapsophobia Tornadoes and hurricanes
Limnophobia Lakes
Lockiophobia Childbirth
Lygophobia Darkness

M
Melissophobia Bees
Menophobia Menstruation
Methyphobia Alcohol
Molysmophobia Contamination, dirt
Murophobia Mice
Mycophobia Mushrooms
Myctophobia Darkness

N
Nebulaphobia Fog
Necrophobia Death
Nosocomephobia Hospitals
Nyctophobia The dark

O
Ochlophobia Crowds
Odynophobia Pain
Oneirophobia Dreams
Ophidiophobia Snakes
Ouranophobia Heaven

P
Pantophobia Everything
Paraskavedekatriaphobia Friday the 13th
Pediculophobia Lice
Pediophobia Dolls
Pedophobia Children
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

18. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Peladophobia Bald people
Phasmophobia Ghosts
Phengophobia Daylight
Philematophobia Kissing
Phobophobia Fear
Phonophobia Noises
Photophobia Light
Pogonophobia Beards
Pteromerhanophobia Flying
Pyrophobia Fire
Q

R
Ranidaphobia Frogs
Rupophobia Dirt
Russophobia Russians
S
Sciophobia Shadows
Scoleciphobia Worms
Scolionophobia School
Selenophobia The moon
Sinophobia Chinese
Sitophobia Food
Sociophobia People
Somniphobia Sleep
Spheksophobia Wasps
Stenophobia Narrow places
Suriphobia Mice
Symbolophobia Symbolism
Symmetrophobia Symmetry
Syngenesophobia Relatives

T
Tachophobia Speed
Taeniophobia Tapeworms
Taphephobia Being buried alive
Taurophobia Bulls
Technophobia Technology
Telephonophobia Telephones
Teratophobia Deformed people
Testophobia Taking tests
Tetanophobia Tetanus
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

19. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Thalassophobia The sea
Thanatophobia Death
Theatrophobia Theaters
Theologicophobia Theology
Theophobia Religion
Thermophobia Heat
Tocophobia Pregnancy
Tomophobia Surgical operations
Tonitrophobia Thunder
Topophobia Certain places or situations
Toxicophobia Poison
Traumatophobia Injury
Tremophobia Trembling
Trichinophobia Trichinosis
Trichopathophobia Hair
Trichophobia Hair
Triskadekaphobia The number 13
Tropophobia Making changes
Trypanophobia Injections
Tuberculophobia Tuberculosis
Tyrannophobia Tyrants

U
Uranophobia Heaven
Urophobia Urine

V
Vaccinophobia Vaccination
Venustraphobia Beautiful women
Verbophobia Words
Vestiphobia Clothing
Virginitiphobia Rape
Vitricophobia Step father

W
Wiccaphobia Witches and witchcraft

X
Xanthophobia The colour yellow
Xenophobia Foreigners
Xerophobia Dryness
Xylophobia Forests
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

20. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Y

Z
Zelophobia Jealousy
Zoophobia Animals



Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

21. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Panic disorder
Epidemiology
1.ECA study – 1 month (0.5%), 6 months (0.8%), life time (1.6%)
2.NCS – 12 months (2.7%) life time (4.7%)
3.females > males
4.Less prevalent in older
Risk factors
1.Early life trauma or maltreatment
2.Anxious temperament that is characterised by neuroticism and anxiety sensitivity.
3.Cigarette smoking and nicotine dependence in adolescence - implicated as risk
factors for later onset of panic disorder, although the cause of this association has
been questioned.
Clinical features
●Recurrent attacks of severe anxiety which are not restricted to any particular situation or
set of circumstances and therefore unpredictable.
●Individual attacks lost only a few minutes though duration and frequency varies
●Experiences a crescendo of fear and autonomic symptoms which results in exit from
wherever he or she may be
●Panic attacks are not unique to panic disorder
●Limited symptom attack​ - If panic attacks occur with fewer than 4 of 13 panic symptoms

Nosology
ICD-10
Several severe attacks of autonomic anxiety should have occurred in past 1 month-
1.In circumstances where here is no objective danger
2.Without being confined to known or predictive situations
3.Comparative freedom from anxiety symptoms between attacks (anticipatory anxiety can
be present)
●In cases where panic attack is occurring in established phobic situation, phobia should be
given diagnostic preference.
●Panic attacks may be secondary to depression and if criteria for depression is fulfilled at
the same time then panic disorder should not be given as main diagnosis
DSM – IV
Recurrent unexpected panic attack, defined as a discrete period of intense fear or discomfort in
which four (or more) of the following symptoms develop abruptly and reach a peak within 10
minutes:
1.Palpitations, pounding heart
2.Sweating
3.Trembling or shaking
4.Shortness of breath or choking
5.Feeling of choking
6.Chest pain or discomfort
7.Nausea or abdominal distress
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

22. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
8.Feeling dizzy, light-headed, or faint
9.Derealization or depersonalization
10.Fear of losing control or going crazy
11.Fear of dying
12.Chills or hot flushes
13.Paresthesias
At least one of the attacks followed by one month (or more) of one (or more) of the following:
1.Persistent concern about having additional attacks
2.Worry about the implications of the attack or its consequences
3.A clinically significant change in behavior related to the attacks
●Panic attacks not due to the direct physiological effects of an illicit substance (or a
prescribed medication) or a general medical condition (e.g., hyperthyroidism)
●Panic attacks not better accounted for by another mental disorder, such as social phobia
(on exposure to a feared social situation), a specific phobia (during exposure to a specific
situation that prompts a phobic response), post-traumatic stress disorder (in response to
stimuli associated with a severe stressor), or separation anxiety disorder (in response to
being away from home or from a close relative)


Relation between Panic disorder and agoraphobia
●In DSM agoraphobia is described as occurring in response to panic attacks (agoraphobia
without history of panic disorder) or panic like symptoms (agoraphobia without history of
panic disorder).
●Not universally accepted and in ICD – agoraphobia is a distinct disorder and diagnosis of
panic disorder with agoraphobia is given only if primary diagnosis of agoraphobia is
excluded
Epidemiological studies
●Agoraphobia 20 times more common in patients with panic compared to controls –
prevalence of 22 to 58% among PD
●Most individuals with agoraphobia do not have panic disorder (only 36% had in NCS)
●ECA – prevalence of Agoraphobia without PD 5.6% but prevalence of PD – 1.6%
Clinical studies
●Diagnosis of agoraphobia without history of panic is rare or non existent
●Agoraphobia is a sequel of panic disorder and is a severe form of panic disorder
●Few studies have found higher prevalence and earlier mean age at onset
Family and genetic studies
●Increased risk of panic disorder in relatives of probands with either panic disorder or
agoraphobia with panic attacks
●Increased risk of agoraphobia in relatives of probands of agoraphobia only
●Suggestive of the position that panic disorder and agoraphobia are different manifestation
of single underlying disorder
Conclusions
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

23. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
●In clinical settings agoraphobia most often appears to be associated with panic Panic
attacks are strong risk factors for development of agoraphobia and panic attack precede or
coincide with onset of agoraphobia in patients of panic disorder with agoraphobia
●Agoraphobia is not always a consequence of panic attacks
●Presence of both is associated with a more severe and chronic course when compared to
panic disorder alone
Comorbidity
1.Depression
a.2/3 pt with Panic Disorder
b.May predate or emerge after onset of Panic Disorder
c.Increased risk of suicide in pts of depression with Panic attacks
d.Increased risk of suicide in pts of Panic Disorder with comorbid depression
2.Alcohol abuse and dependence
a.In 25% patients of Panic Disorder
b.?? Attempt to self medicate
c.A relative contraindication to use of BZD
3.Nicotine use
a.
4.BPAD
5.GAD
6.Social phobia
a.Focus on core fears help in diagnosis – in panic central fear is having another
attack while in social phobia focus is mainly on possibility of humiliation or
embrassment
7.Social phobia, OCD, PTSD

Differential diagnosis
1.Depression
a.Temporal onset of symptoms
b.Decreased vegetative symptoms – no anhedonia/ diurnal variation/ loss of
appetite/ early morning awakening (difficulty falling asleep may be present)
2.Hyperthyroidism
3.Cardiac disease - IHD, arrhythmias
a.Mitral valve prolapse occurs more frequently in patients with panic
disorder
b.No increased prevalence of panic disorder in patients with mitral valve
prolapse
c.No full blown symptoms of panic are present in pts with only MVP but pts
of PD with or without MVP are same
d.May represent different manifestation of autonomic dysfunction
e.A meta analysis has shown significant association between panic disorder
and mitral valve prolapse
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

24. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
f.Few reports are present in which treatment of panic disorder resulted in
correction of mitral valve prolapse – few theorise that tachycardia caused
by panic causes MVP
4.Hyperparathyroidism
5.Pheochromocytoma – only physical symptoms will be present and anticipatory
anxiety will not be present
6.Hypoglycemia
7.Disease of vestibular nerve


Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

25. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Etiology
●Biological
●Psychological
Genetic
●Heritability – 40%
●Family members – 8 times increased risk
●Monozygotic 5 times greater than dizygotic
●Chromosome linkage
o13- ​type of panic disorder associated with bladder problems (possibly urinary
interstitial cystitis)
o18- ​subtype of bipolar illness associated with panic attacks
o9- identified through genome wide scanning – also associated with
cigarette smoking
●Candidate genes –
oadenosine 2a receptor
oCCK – chromosome 11and 1
oCOMT – chromosome 22
oSerotonin transporter, norepinephrine receptor – iconsistent
Neurobiological process - findings
GABA
●Beta carboline – inverse agonist of BZD – produces anxiety symptoms
●BZD – effective in treatment
●Flumazenil – panicogenic in panic disorder patients
●Decreased BZD receptor binding in hippocampus and prefrontal cortex on PET
and SPECT
Serotonin
SSRI effective in treatment
Tryptophan depletion increases anxiety
No direct evidence
HPA axis
Inconsistent findings
Uncoupling of noradrenergic and HPA axis activity in panic disorder patients
Sympathetic nervous system
Isoproterenol – produces panic attacks (beta adrenergic hypothesis)
Electrical stimulation of locus coeruleus – panic attacks
Yohimbee – induces anxiety
Sodium lactate
Provokes panic in patients only not in normal people
Carbon dioxide hypersensitivity (False suffocation alarm theory)
In panic patients, hypersensitivity of brain stem CO2 chemoreceptors is present which
results in hyperventilation and panic attacks ( as seen in experimental conditions of
breathing 5% CO2)
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

26. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Imaging
●Reduced volumes in amygdala and temporal lobe
●Lowered amounts of creatine and phosphocreatine metabolites in the medial
temporal lobe
●Decreased cerebral glucose metabolism in amygdala, hippocampus, thalamus, and
brain-stem areas
●Reduced orbitofrontal blood flow that predicts panic response to doxapram
●Reductions in 5HT1a receptor concentrations
●Decreased BZD receptor binding in hippocampus and prefrontal cortex on PET
and SPECT
Neurocircuitry of panic disorder – Fear circuit
The amygdala has a crucial role as an anxiety way-station that mediates incoming stimuli
from the environment (thalamus and sensory cortex) and stored experience (frontal cortex
and hippocampus; dark arrows), which affects the anxiety and panic response by
stimulating various brain areas responsible for key panic symptoms (red arrows). The
periaqeductal gray in the midbrain could be especially important for mediating
panic-anxiety. Drug treatments can target all parts of this system, aff ecting amygdala and
frontal-lobe interpretation of stimuli, or output effects. Cognitive-behavioural treatment
aff ects the frontal-lobe areas, especially in the medial prefrontal cortex, which is known
to inhibit input to the amygdale by using a braking action.




Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

27. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin




Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

28. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Cognitive behavioral theory
Initial panic attack is viewed as an unexpected firing of emergency fright-flight response
occurring during or after a period of stress. Subsequent panic attacks are viewed as reactivaftion
of this alarm response but in response to subjective danger. The factors responsible for the
subjective danger are
1.Catastrophic misinterpretation – perceiving normal anxiety responses as indicative of an
immediately impending physical or mental disaster
2.Conditioned fear response to aversiveness of attack- with repeated attacks individual
become more and more sensitized to situational and internal cues that herald panic attacks
These results in,
1.Anxious anticipation and hypervigilance – leads to chronic arousal and individual
becomes aware of minute physiological sensations
2.Avoidance – avoids activities associated with such sensations and also situations
These anxiogenic responses to internal cues (fear of fear) maintains the disorder.





Cognitive behavior therapy

The two major forms of CBT developed for panic disorder have been Barlow and Craske’s panic
control treatment, and Clark’s cognitive therapy for panic.

The treatment aims at,
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

29. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
1.Vigilance to and catastrophic misinterpretation of somatic sensation
2.Conditioned fears of body sensations
3.Chronic arousal
4.Myriad avoidance reactions
The elements of CBT for panic disorder usually involve five components.
1.Informational component – includes an overview of fear of fear cycle and provides and
rationale for treatment interventions
2.Somatic management skills – Breathing retrainig and relaxation (JPMR or applied
relaxation)
3.Cognitive restructuring – decatastrophizing beliefs about somatic symptoms and the
tendency to overestimate the probability of negative outcomes. The cognitions are
evaluated through Socratic questioning by examining the evidence for and against
cognitions. Self monitoring procedures can also be used.
4.Interoceptive exposure – To bring on the physiologic symptoms associated with panic
within the treatment sessions and home based practice. Commonly administered exercises
include – chair spinning, head rolling, straw breathing, breath holding, mirror gazing, step
ups. The goal is to break the association between heightened somatic response and
anxiety. With repeated exposure patient gets habituated to adverse symptoms. Later these
interoceptive exposures are replaced by naturalistic exposure – procedures like exercise,
caffeine drink which will produce somatic sensations.
5.In vivo exposure – exposure to avoided situation

Psychodynamic psychotherapy
Psychodynamic theory of panic –
Anxiety is generated when danger situations are activated
These danger situations are unconscious and include threatened emergence of prohibited
instinctual urges impending disruption of self o object representations.
Treatment focus​ –
Elucidation of unconscious sources of anxiety and associated characterologically based
maladaptive behaviors. Curative components of treatment are establishing a transference
relationship and acknowledgement of troublesome angry feelings held by the patient that are
associated with panic attacks.




Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

30. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Generalized Anxiety Disorder
Introduction
First introduced in DSM-III (1980)

Epidemiology
●Epidemiological studies in Europe suggest that the illness has a lifetime prevalence of
4·3–5·9% and a probable 12-month prevalence of 1·2–1·9%.
●Co morbidity with major depression is present in three out of five cases and a similar
proportion have other anxiety disorders.
●ECA study – women : men = 2:1
●NCS → current prevalence 1.6%, 1 year 3.1%, lifetime 5.1%
●More common in unemployed, divorced, separated, widowed and older
Children ​– ​Overanxious disorder prevalence 2.9%,male:female=1.7:1 (newzeland study). Virginia
twin study - Overanxious disorder 4.4%, girls:boys= 2:1
Elderly​- ​6 month prevalence 1.9% life time 4.6% for age >65 years (ECA and NCS)

Clinical features
Nosology
ICD-10
The sufferer must have primary symptoms of anxiety most days for at least several weeks at a
time and usually for several months. The Sx should involve
1.apprehension – worries about future misfortunes, feeling on the edge, difficulty
controlling
2.Motor tension – restless, fidgeting, tension headaches, trembling, inability to relax
3.Autonomic hyperactivity – light headedness, sweating, tachycardia, tachypnea, epigastric
discomfort, dizziness, dry mouth
In children need for reassurance and recurrent somatic complaints may be prominent

DSM- IV
●The patient reports having excessive anxiety and worry (apprehensive expectation),
occurring more days than not for at least 6 months, about a number of events or activities
(such as work or school performance).
●The patient has difficulty in controlling worry.
●The anxiety and worry are associated with three or more of the following six symptoms
(with at least some symptoms present for more days than not for the previous 6 months):
(In children only one of six is essential)
1.Restlessness or feeling keyed up or on edge
2.Being easily fatigued
3.Difficulty concentrating or mind going blank
4.Irritability
5.Muscle tension
6.Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep).
●The focus of the anxiety and worry is not confined to features of other types of
psychiatric disorders (e.g., panic disorder, social phobia, obsessive–compulsive disorder,
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

31. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
separation anxiety disorder, anorexia nervosa, somatization disorder, or hypochondriasis),
and the anxiety and worry do not occur exclusively as part of post-traumatic stress
disorder.
●The anxiety, worry, or physical symptoms cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.




Description
Pathological worry - pathognomonic
1.The areas of worry are similar to that of non anxious people such as family and
interpersonal relationships, work, school, finances and health.
2.GAD worry is perceived as significantly more uncontrollable and unrealistic. People with
GAD spend more of the day worrying than non anxious control subjects.
3.GAD patients have excessive worry over minor matters – daily hassles and time
management
4.GAD people do believe that worry serves to distract them from more emotional topics
In children and adolescents –
Earlier (DSM III) diagnosed as overanxious disorder. In DSM IV it is subsumed under GAD.
Only one of six is required and in ICD- need for reassurance and recurrent somatic complaints
may be prominent.

Differential diagnosis
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

32. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin

1.Normal anxiety
GAD Normal anxiety
Perceived as significantly more uncontrollable
and unrealistic
Not
spend more of the day worrying Less time
worry over minor matters Absent
Manifests as physical symptoms Absent
catastrophic cognitions present Absent
Functionally disabling Usually facilitating

2.Dysthymia and depression
a.Vigilance, scanning and respiratory symptoms are more prominent
b.Severe depressive symptoms, suicidality and hopelessness points depression
3.Hypochondriasis – disease conviction is the key
4.Panic disorder – focus on acute cardiopulmonary symptoms


Comorbidity
●More than 2/3 patients have one or other axis I disorder- social phobia and panic disorder
are leading.
●20% of depression and 10% of other anxiety disorder have co morbid GAD
●Axis II –
o50% of GAD has personality disorder- avoidant, dependent and OCPD.
oPersonality doesn’t predispose to development of anxiety disorder
oSome personality may be secondary to anxiety disorder

Course
●Chronic, fluctuating severity.
●Onset- commonly in 20s. >6- uncommon. <10= malignant type.
●Late onset GAD – rapidly progressive, stressor present
●Early onset – Gradual onset, more comorbid
●40 year follow up study – acta 2007- Improvement was observed in 83%. GAD tended to
disappear around age 50, but was replaced by somatization disorders. Lack of regular
treatment compliance, female sex, and onset of GAD before age 25 were variables
associated with a worse outcome.

Assessment –rating scales
Hospital Anxiety and Depression Scale
Hamilton rating scale for anxiety

Etiopathogenesis
Neurobiology
1.Genetic
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

33. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
2.Neurochemistry
3.Endocrine
4.Neuroimaging
5.Neurophysiology
Genetics

Family studies​ - elevated risk of the index anxiety disorder in first-degree relatives, but that other
anxiety disorders are not increased. Odds ratio 6.1.

Twin studies​ - A concordance rate for GAD of 21.5% (13/63 twin pairs) in MZ twins, compared
with a 13.5% (11/81) concordance rate in DZ twins. 31.6% of the variance for liability to
generalized anxiety disorder was attributable to additive genetics in both genders and that the
same genes predispose men and women to generalized anxiety disorder.

Adoption studies​ - there have not been any adoption studies of anxiety disorders


Neurochemistry
1.Norepinephrine
a.Elevated catecholamine levels, downregulation of post synaptic alpha 2 receptor,
blunted response of growth hormone to clonidine, hyperactivity of locus
coeruleus is noted.
b.No sensitivity to yohimbene. pheochromocytoma (source of catecholamines
outside CNS ) fails to elicit anxiety → elevated catecholamine may be the result
of GAD
c.Norepinephrine has a role in GAD, but does not definitely indicate a causative
role
2.Serotonin
a.Both hyperactivation (increased 5 HIAA) and underactivation (PCPA induced
anxiety) has been reported.
b.Receptor subtypes is important – 5HT1A, 5HT2​A​ AND 5HT2C have been
implicated
3.GABA
a.Decreased benzodiazepine receptors in platelets, lymphocytes
b.Reduced sensitivity of saccadic eye movements → down regulation of central
BZD receptors
c.Benzodiazepine and GABA dysfunction underlie in the initiation and propagation
of GAD
4.CCK
a.CCK4 and CCK8 have been the most interesting and CCK-B receptor type is
widely distributed in CNS
b.CCK dysfunction contributes to anxiety proneness through its influence on
noradrenergic system. CCK agonist pentagastrin produces panic attacks.
c.CCK acts on GABA system also in an opposing manner to benzodiazepines.
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

34. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
d.Human studies of CCK-B antagonists in GAD are negative.
Endocrine functions in GAD
1.CRF
a.Norepinephrine and serotonin potentiates the release of CRF
b.Animal studies reveal that CRF administration causes arousal, but in humans
CSF levels of CRF are not significantly different between GAD and normal
2.Cortisol
a.Elevated level of cortisol is seen in patients with GAD- 27 to 38% of patients are
non suppressors on dexamethasone test.
b.State marker- all these patients reverted to suppressors after treatment
c.HPA axis is over activated in GAD and plays a role in perpetuating the disorder.
Neurophysiology
1.ECG- Patients with GAD have shorter inter beat intervals on ECG indicating lowered
cardiac vagal control and autonomic inflexibility. These patients have weakened response
to stress and require longer to recover from stressor.
2.EEG- sleep profile indicates decrease in slow wave sleep, but none of the REM
disturbances seen in depression. But the same sleep profile is seen in dysthymia.
3.Skin conductance- No difference between cases and controls except takes longer time
return to base line following a stress.
4.Have higher cholesterol and triglyceride level presumably because they are exposed to
increased noradrenergic activity.
Neuroimaging
1.Anxiety scores correlate with changes in glucose metabolism in limbic system and basal
ganglia, but no change in the right and left parahippocampal gyrus.
2.Relative increase in metabolism is seen in cerebellum, occipital lobe, left inferior frontal
gyrus, right precentral frontal gyrus and decreased in basal ganglia, temporal lobe and
cingulate gyrus.
3.During vigilance relative increase in basal ganglia and right parietal metabolism is seen
and decrease in right temporal and occipital lobe – stimulus processing may be
dysfunctional in GAD.
4.Those with high basal anxiety had a decrease in cerebral blood flow as they became more
anxious compared to those with low baseline anxiety, consistent with loss of the capacity
to mount an adaptive stress response.
5.In conclusion basal ganglia, temporal and occipital lobes have been consistently
implicated. Cerebral blood flow may be altered in GAD and paradoxically these
hyperaroused individuals have decrease in flow during stress.

Psychological theories

Risk factors
Parent-child relationship
Trauma
Temperament
Information processing
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

35. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin

Early childhood
●Behavioral inhibition defined as the childhood temperament characterized by a tendency
to be shy and timid in novel situation is a potential predictor for later anxiety disorders.
●Adults with GAD viewed their parents as rejecting and controlling
●Anxious children’s families are less cohesive and more enmeshed than control’s families
●Effect of trauma and its contribution to development of anxiety disorders is not supported
by all studies and likely contribute to the onset of GAD
Insecure attachment hypothesis​ – Feelings of enmeshment or role reversal and pre occupying
anger and oscillating feelings towards the primary care giver. Parental overprotection and lack of
warmth may also contribute.

Role of worry –​ People with GAD also involve more in thoughts than images while worrying.
Worry contributes​ ​to the persistence of GAD in no of ways like,
1.Worry minimizes the negative affect.
2.Content of worry- because the worry is about future, the chances of this occurring is very
low and this has no behavioral solution which leads to further ruminations and worry.
3.Individual believes that worry has assisted in successfully avoiding the negative situation.


Cognitive behavior theory
Automatic thoughts​- self reinforcing and prevent the person from approaching a novel situations
without great anxiety.
Attentional bias
●Due to worry people with GAD have bias attention towards threat related information
●Selectivity of attention​- Individual with GAD has distress over threat related information
even when it is embedded with positive information. This has been shown by bias
towards the threat related words on emotional stroop task and lexical decision task
(individual letters are presented briefly and asked to judge whether they constitute a
word).
Threat related interpretation of ambiguous stimuli​- Patients with GAD worry about catastrophic
consequences from unclear situations. Individuals with GAD select threat related interpretations
of stimuli or generate threat-related interpretations when the contexts are ambiguous. Support has
been generated from the tests using homophones (die VS dye)
Memory bias​-
o Bower’s model of mood congruent memory states that positive or negative mood
state facilitates memory for semantic information of similar valence and inhibits
the information of dissimilar valence.
oUnlike the robust findings in depression the findings in GAD are mixed.
oHowever threat related information may be encoded more than the non threat
related information and later affect the cognitive functioning without conscious
effort. Preliminary support is by using a perceptual identification test to test the
implicit memory bias.
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

36. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
oIn GAD attentional bias towards threat have been hypothesized to occur during
activation stage of word processing than elaboration phase.
Problem solving
●Worries may have higher evidence requirements before making a decision that is when
faced with an uncertain threat or an ambiguous situation, patients with GAD may require
more time for decision making.
●The reasons for low problem solving capacity may be
oGAD persons have higher need for perfectionism
oThey have difficulty tolerating uncertainty, which leads them to consider
ambiguous events as threat
oLack of confidence in cognitive ability
Worry in people with GAD has been hypothesized to be associated with an increased sensitivity
to threat related cues, negative interpretation of ambiguous stimuli, facilitated activation of threat
related memory and deficits in problem solving. These cognitive processing biases will in turn
lead to result a state enhancing the worry leading to a self perpetuating cycle.

Barlow’s model
Negative life events trigger stress related neurobiological reactions. This leads the person to focus
on life events, even minor ones and to react to these events with a negative affect. This in turn
leads to shift his focus from task at hand to self evaluation which leads to further arousal.

Etiological models
1.Kendler​- Genetic influences for the development of depression and GAD are identical.
Environment determines which disorder the patient will develop. It doesn’t explain the
neurophysiological differences or comorbidity.
2.Gray – Behavioral inhibition system- Septohippocampal area is responsible for
processing threat related stimuli. Presence of danger activates this system and results in
increased arousal and inhibition of regular behavior
3.Charney – Central role of amygdale in regulation of anxiety. When faced by threatening
information, the stimulus processed in the context of past, experience and amygdale-
orbitofrontal cortex choose anxiety response, which is mediated by locus coeruleus,
hippocampus and brain stem structures. Fails to address what factors predispose one to
develop this dysfunction.
4.Cloninger- Inherited abnormalities in neurotransmitters cause personality traits that could
manifest as GAD. Extremely high and low level of harm avoidance predispose
individuals to chronic anxiety. Those with high novelty seeking will develop somatic
anxiety and those with low novelty seeking and low reward dependence will develop
cognitive anxiety.
Treatment

Pharmacoogical
1.Antidepressants
2.Anxiolytics

Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

37. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
Different classes of medications are similarly efficacious in GAD. The choice of drug depends on
a.Perceived adverse effect profile –
a.SSRI better than TCA.
b.If restlessness and insomnia present, TCA better than SSRI
c.
b.Comorbid depression – Antidepressants are preferred
c.Need for rapid action – Benzodiazepines(hours) are preferred than antidepressants
(4weeks)
Evidence basis
SSRI – Best evidence for paroxetine (effect size range from 1.8 to 3.6). DBRCT for sertraline and
escitalopram. No particular studies in fluoxetine, fluvoxamine, citalopram
Venlafaxine- effect size of 2.7 in DBRCT
BZD- beyond doubt proven in many DBRCT
Pregabalin – one DBRCT
TCA- DBRCT proven efficacy – less no of trials
Buspirone , hydroxyzine - DBRCT
Treatment resistance – No controlled trials. Only anecdotal reports- combination of methods
Combination of pharmacotherapy with CBT – Only two studies, in which one showed the
How long to continue??
Minimum of 6 months. Trials are with paroxetine and venlafaxine upto 6 months and have shown
decreased relapses compared to placebo.

Antidepressants
1.Except pure noradrenergic drugs like bupropion, desipramine most agents are efficacious.
2.Antidepressants have better effect than benzodiazepines when comorbid depression,
OCD are present
3.SSRI, TCA, SNRI all are effective
4.NNT was 5.1 (Cochrane review)
Anxiolytics
1.Benzodiazepines
a.Havde rapid anxiolytic property
b.Different types of benzodiazepines have equal efficacy
c.Dependence and abuse are important limiting factors
d.May exacerbate hostility and impulsivity in some patients
e.Causes psychomotor, cognitive and memory deficits
f.Tapering is difficult because of rebound anxiety
2.Buspirone – preferred in patients who do not demand immediate relief of symptoms, do
not have comorbid depression, who have not been given benzos earlier (in those who
received BZD earlier buspirone is less effective though controversial). Started with 5 mg
thrice a day and increased up to 60 mg.
a.5HT1 agonist
b.Effective – NNT (number needed to treat) is 4.4
c.Not addicting. Can be used safely in long term treatment also
d.May be specially useful in those with ADS
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

38. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
e.Better side effect profile than BZD and no rebound anxiety
f.Initially may cause periods of dysphoria
3.Hydroxyzine
a.Efficacy is proven in double blind placebo trials
b.No rebound effect/ cognitive deficit
c.As effective as lorazepam
Second line drugs
1.Propranolol – useful if there is marked somatic manifestation of anxiety
2.MAOI-
a.Phenelzine is effective, but moclobemide is not as effective
b.Useful in intractable severe anxiety
c.Even when other agents have failed, phenelzine is useful
3.Antipsychotics – may be used as augmentation agents
4.Preegabalin
Treatment resistance – no specific guideline exists. Combination of treatments may be useful.


Psychosocial

Cognitive behavior therapy –
1.Psycho education-
a.Clarify the misconceptions and misunderstandings
b.Biopsychosocial model
c.Relief by knowing that their problem is not uncommon
d.Facilitates the treatment compliance
2.Self monitoring –
a.helps both as an assessment procedure and treatment strategy
b.Each time patient feels anxious, should record when and where the anxiety began
and intensity of experience, including the symptoms that were present.
3.Cognitive restructuring –
a.Observe the automatic thoughts – to bring them in to awareness. This is achieved
by self monitoring, Socratic questioning, role playing, imagery, filling a thought
record
b.Introduce the cognitive distortions – overestimation, catastrophizing, all or none
(black and white) thinking
c.Challenging the distortions
4.Relaxation – To reduce the physiological correlated of anxiety. It helps in
a.Broadening the focus- patient can consider alternatives in anxiety provoking
situation
b.Serves as distraction
c.Activation of anxious thoughts – exposure of thoughts
5.Worry exposure –proposed by Brown
a.Concept is to have the patient activate the worst possible outcome in order to
process it and habituate the anxiety associated with it.
Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava

39. “Honesty may be the best policy, but it's important to remember that apparently,
by elimination, dishonesty is the second-best policy.”
― George Carlin
b.Patients purposely expose themselves to both worry and images associated with
worry for an extended period.
c.Habituation of anxiety is facilitated by cognitive challenging after patient focuses
on image for around 20 o 30 minutes
6.Stimulus control – Borkovec
a.Patients are asked to postpone the worry when it begins to occur and write down
all the worries and then set aside an hour in the evening to worry.
7.Worry behavior control
Patient’s preoccupation with worry and its reduction distracts him from original source of
negative state (like fear or depression). Therefore eliminating the worry behavior
allows the patient to fully experience and process the worry.
a.Detection of avoidance behavior – both explicit and subtle- by questioning,
monitoring and assessment
b.Similar to ERP patient is asked to refrain from these behaviors when worried
c.Hierarchies are created and patient is gone through the same
Supportive therapy and psychodynamic therapy have been practiced but not having an evidence
basis. In few studies supportive therapy was as efficacious as CBT but other studies show
superior efficacy of CBT.



Non nobis solum nati sumus
(​Not for ourselves alone are we born ​)
-Dr. Eashan Srivastava