Anxiety disorders

Karen G. Martinez, MD, MSc

Assistant Professor
Department of Psychiatry

Objectives
Discuss the epidemiology and clinical
characteristics of anxiety disorders
Understand the biological basis of anxiety
disorders
Present the psychological and social theories
involved in the expression of anxiety disorders
Overview treatment options for these conditions
Discuss changes to anxiety disorders with the
DSM V
Present research finding on anxiety disorders in
Puerto Rico

Anxiety
Emotional uneasiness associated with the
anticipation of danger
NORMAL emotion: can be protective and
adaptative
Developmentally normal episodes of
transient anxiety in children and
adolescents

Maladaptative anxiety
Causes significant distress
Causes marked dysfunction in
academic or social functioning
Disproportionate reactions
Spending excessive amounts of time
to eliminate anxiety

Increased
activity in
amygdala
Decreased topdown control of
pre-frontal
cortex
Faulty
hippocampus
interpretation of
threat/safety
signals

Hippocampus

Etiology of anxiety disorders

Can be classified as disorders with faulty fear
circuits
Panic disorder
Phobias
PTSD

More cognitive pervasive anxiety

GAD

Obsessive-Compulsive Disorder
Trauma and Stressor-Related Disorders

Biological etiology: genetics

Serotonin transporter gene

Biological etiology: temperament

Behavioral inhibition (Kagan)
Avoidance of novelty and challenge
Suppression of spontaneity to unfamiliar objects,
people and situations
React to unfamiliarity with avoidance, distress, or
subdued emotion

Associated with later onset of anxiety disorders

and family history of anxiety

Biological etiology: personality and

cognitive process
Neuroticism vs
Extraversion
Trait anxiety
Attentional bias
to threat

Pine et al, 2013

Cognitive theory of anxiety disorders

Sometimes phobic behavior linked to specific
experiences, e.g.,
Attacked by dog
Bad public speaking experience
Evolutionary preparedness
Fear snakes, spiders, angry rejecting people
Do not fear electrical outlets, flowers, babies

Cognitive
distortions

DSM 5 Anxiety Disorders

Anxiety disorders

Separation anxiety disorder

Selective mutism
Specific phobia
Social anxiety disorder
Panic disorder
Agoraphobia
Generalized anxiety disorder
Substance/medication-induced anxiety disorder
Anxiety disorder due to another medical condition
Other specified anxiety disorder
! Ataque de nervios

Unspecified anxiety disorder

Luis is a 27 years old teacher who comes to the

ER because of sudden chest pain with
palpitations, difficulty breathing and feelings of
choking, sweating and nausea. He says that he
Panic attack
was calm and suddenly started having these
symptoms. He thought he was going to die. The
symptoms lasted for 7 minutes and then slowly
disappeared. Luis wants to know if he just had a
heart attack.

Luis is a 27 years old teacher who comes to the

ER because of sudden chest pain with
palpitations, difficulty breathing and feelings of
choking, sweating and nausea. He says that he
was calm and suddenly started having these
symptoms. He thought he was going to die. The
symptoms lasted for 7Panic
minutes and then slowly
disorder
disappeared. Luis says that he has been having
one or two of these attacks for the last month
and he has stopped going out with friends for
fear of this happening. He cannot identify a
trigger and says they happen out-of-the-blue.

Course of illness and prognosis

Course of illness is variable
Wax and wane

Outcome

About 33% recover, 50% have limited impairment, 20% had

severe impairment

Predictors of worse prognosis

More severe initial panic attacks

More severe initial agoraphobia
Longer duration of illness
Comorbid depression
History of separation from parent
High interpersonal sensitivity
Single marital status

Differential diagnosis
Other anxiety disorders
Depersonalization disorder
Personality disorders
Thyroid problems
Mitral valve prolapse
Pheochromocytoma
Cardiopulmonary conditions
Vestibular dysfunction
Seizures

Luis is a 27 years old teacher who comes to the

ER because of sudden chest pain with
palpitations, difficulty breathing and feelings of
choking, sweating and nausea. He says that he
Specific
was calm but then hePhobia
saw a cockroach. Luis has
been afraid of cockroaches since he was a child
and always avoids places where he knows he can
find them.

Specifiers phobia
Animal
Natural environment
Blood-injection-injury
Situational
Other

Luis is a 27 years old teacher who comes to the

ER because of sudden chest pain with
palpitations, difficulty breathing and feelings of
Socialnausea.
Anxiety
choking, sweating and
He says that he
Disorder
was calm until he had
to make a report on his
students performance in a teachers meeting.
He says he could not stand everyone looking at
him and that he had been dreading this meeting
all week. He can remember avoiding public
speeches since he was a child. This fear has kept
him for pursuing a masters degree.

Course of illness and prognosis

Early onset (before adolescence)
Chronic course
Outcome
Only half recover after many years of treatment

Predictors of poor prognosis

Onset before 8-11 years old
Psychiatric comorbidity
Low educational status
Comorbid health problems

Differential diagnosis

Normal shyness
Other anxiety disorders
Obsessive compulsive disorder
Body dysmorphic disorder
Delusional disorder
Major depressive disorder
Personality disorders

Paranoia
Depression
Autism spectrum disorder
Pragmatic communication disorder
Oppositional defiant disorder

Avoidant, schizoid

Luis is a 27 years old teacher who comes to your

office because of excessive worrying in the past
year. He states that he worries about
everything and that he cannot control this
worry. He also hasGeneralized
been feeling restless, tired
Anxiety
and irritable. He has
had difficulty
Disorder
concentrating and sleeping as well as muscle
tension.

GAD
Diagnosed after ruling out all other Axis I
disorders as source of anxiety
Often chronic
Worsens with stress
Probably the least studied anxiety disorders

Differential diagnosis
Other anxiety disorders
Obsessive compulsive disorder
Post traumatic stress disorder
Major depressive disorder
Illness anxiety disorder
Personality disorders

Luis is a 7 years old child who comes to your

office because of recurrent abdominal pain for
the last 1.5 months. This pain is usually worse in
the morning and on school days. He also
Separation
complains of pain when
his father has to go to
disorder
work on Saturday. anxiety
He has
not been able to go
to school this week and his mother has stayed
home with him with some improvement in the
pain. Upon evaluation, abdominal exam is
unremarkable. His symptoms started two weeks
after his mother had a motor vehicle accident.

Separation Anxiety Disorder

(SAD)
Inappropriate fear and anxiety regarding
being apart from home or from primary
attachment figure
Symptoms present for more than 4 weeks
Age appropriate 7 mo- 6 years old
Prevalence: 2.4-5.4%

SAD
Differential diagnosis

Obsessive Compulsive Disorder

Other anxiety disorders
Conduct disorder
Illness anxiety disorder
Depression
Post Traumatic Stress Disorder
Disruptive disorders
Bereavement
Psychosis

SAD
Course and outcome
Many cases improve spontaneously
Risk factors for complication:
! Later age of onset
! Comorbidity
! Family psychopathology
! Missing > 1 year of school

Selective mutism
Persistent failure to speak in social situations
despite speaking in other situations
Seen in association with shyness, fear of
embarrassment and social withdrawal
Symptoms must be present > 1 month
Not clearly associated with trauma or with a
communication disorder

Induced Anxiety Disorders

Substance/Medication
Alcohol, caffeine, cannabis, phencyclidine, other
hallucinogen, inhalant, opioid, sedative/hypnotic/
anxiolytic, amphetamine, cocaine, other

Due to another medical condition

Other specified anxiety disorder

Ataque de nervios
Described among Latinos
Intense emotional upset including acute anxiety,
anger or grief, trembling, uncontrollable
screaming or crying, aggressive or suicidal
behavior, and depersonalization or derealization
Can be experienced longer than a panic attack
Includes dissociative symptoms

Luis is a 22 years old student who comes to your

office because of recurrent intrusive thoughts
about having killed his mother. Luis says these
thoughts are horrible to him and he would never
harm anyone, especially his mother. He says he
Obsessive
started having intrusive
thoughts when he was 9
compulsive
and thought he coulddisorder
get contaminated by
touching doorknobs. He continued to have
different thoughts throughout adolescence but
nothing as painful as the ones he is having now.
He says he is so worried about killing his mother
that he has to check on her and has moved back
in with her.

Obsessive-compulsive and related

disorders

Obsessive-compulsive disorder
Body dysmorphic disorder
Hoarding disorder
Trichotillomania
Excoriation
Substance/medication-induced
Due to another medical condition
Other specified

Body dysmorphic-like disorder with actual flaws

Body dysmorphic-like disorder with repetitive behavior
Body-focused repetitive behavior disorder
Obsessional jealousy
Culture concepts of distress

Unspecified

Luis is a 22 years old student who comes to your

office because of recurrent intrusive thoughts
about having killed his mother. Luis says these
thoughts are horrible to him and he would never
harm anyone, especially his mother. He says he
started having intrusive thoughts when he was 9
and thought he could get contaminated by
touching doorknobs. He continued to have
different thoughts throughout adolescence but
nothing as painful as the ones he is having now.
He says he is so worried about killing his mother
that he has to check on her and has moved back
in with her.

Common obsessions
Contamination
Harm to self/ others
Aggressiveness
Sexual themes
Scrupulosity/ religiosity
Forbidden thoughts
Symmetry urges
Need to tell, ask, confess

Common compulsions
Washing
Repeating
Checking
Touching
Counting
Ordering/ arranging
Hoarding
Praying

Etiology
OCD is a neuropsychiatric disorder
Soft neurological signs
Nonverbal learning problems

Family genetics studies point to a heritable disease

(especially OCD + tics)
Neuroimaging studies
Abnormalities in basal ganglia-cortex circuits
! MRI: Increased size caudate nucleus
! PET: Increased activity in orbital gyri and caudate
! fMRI spectroscopy: Elevated glutamate in caudate

Abnormalities improve with treatment

PANS (pediatric acute onset neuropsychiatric

syndrome)

Neural circuits and OCD

Neuroimaging OCD

Normal MRIpointing to caudate

nucleus

OCD MRI with

enlarged right
caudate nucleus

Neuroimaging OCD

PET scan in OCD-pointing

To increased activity in
frontal lobes

PET scan before and after

Treatment-pointing to right
caudate nucleus

Course and prognosis

Course
1/3 have a wax and wane course
have a chronic or progressive illness

Predictors of poor prognosis

Early age of onset
Longer duration of illness
Presence of both obsessions and compulsions
Poor baseline social functioning
Magical thinking

Differential diagnosis
Other anxiety disorders
Tics (Tourettes)
Eating disorders
Body dysmorphic disorder
Somatic illness anxiety disorder
Depression
OCPD
Paranoid psychosis

Body dysmorphic disorder

Preoccupation with one or more
perceived defects or flaws in
physical appearance that are not
observable or appear slight to
other
Repetitive behaviors in response
to appearance concerns

Hoarding
Persistent difficulty
discarding or
parting with
possessions
Accumulation of
possessions

Luis is a 22 years old who just came back from a

tour of duty in Afghanistan. He says that he has
been unable to sleep in the past three months
because of recurrent nightmares about an
Post-traumatic
ambush. He also avoids
leaving his house
stress disorder
because loud noises
startle him and he
sometimes has flashbacks about his platoon
members getting hurt. He blames himself for
the ambush as he was driving and he was
received no injuries in the process.

Trauma and Stressor Related Disorders

Reactive attachment disorder
Disinhibited social engagement disorder
Post-traumatic stress disorder (PTSD)
Acute stress disorder
Adjustment disorders

Luis is a 22 years old who just came back from a

tour of duty in Afghanistan. He says that he has
been unableExposure
to sleep
in the
to actual
or past three months
threatened death,
because of recurrent
nightmares about an
serious injury or
ambush. He also
sexualavoids
violence leaving his house
One or more
intrusion
because loud noises startle him and
he symptoms
sometimes has Avoidance
flashbacks
about his platoon
of stimuli
with
members getting associated
hurt.
He
blames himself for
trauma
the ambush as he was driving and he was
Two or more
Negative alterations in
received
no
injuries
in
the
process.
symptoms of altered
cognitions and mood
arousal/reactivity

associated with
trauma

PTSD specifiers time

<1 month duration of symptoms
Acute stress disorder

Symptoms develop >6 months after trauma

With delayed expression

With dissociative symptoms

Depersonalization
Derealization

Risk factors for PTSD

Pretraumatic factors

Childhood emotional problems

Prior mental disorder
Prior traumatic experiences
Lower SES/education
Childhood adversity

Peritraumatic factors

Severity of trauma
Dissociation
Military- being a perpetrator

Posttraumatic factors

Acute stress disorder

Negative coping skills
Subsequent trauma
Repeated exposure to reminders

Biological etiology-PTSD
Chronic stress leads to
dysregulation of the
hypothalamic-pituitaryadrenal axis
Effect of cortisol on
development of amygdala and
hippocampus
Reduced hipoccampal
volume in adults

Course and prognosis

Course
80% have symptoms for more than 3 months
75% longer than 6 months
50% longer than 2 years

Traumatic events increase a persons suicide risk

Clinical expression may vary culturally
Panic attacks might be salient in Latinos because
of ataque de nervios

Differential diagnosis
Adjustment disorder
Either stressor does not meet criteria for PTSD or
other PTSD symptoms are not present

Acute stress disorder

Depression
Other anxiety disorders
Dissociative disorders
Conversion disorder
Psychotic disorders

Anxiety disorders in children and

adolescents
Prevalence: 10-20% school-age children
exhibit anxiety
5-18% children in community samples have an
anxiety disorder
Preadolescent clinical samples: 0.3-12.9%
Adolescent clinical samples: 0.6-7%

Most prevalent disorders: specific phobias,

SAD, GAD

Developmentally appropriate
anxiety
8 mo: stranger anxiety
Up to 24-36 mo: separation anxiety
Pre-school age: phobias (dark, monsters,
animals)
School age: performance anxiety,
supernatural/natural phenomena

Difference in diagnostic criteria for

children
Panic disorder

Diagnosis is controversial in children/adolescents

Cognitive capacity of children usually poses external causation of internal symptoms

Specific phobias
Anxiety may be expressed by crying, tantrums, freezing, or clinging.
Insight might be absent

Social phobias

There must be evidence of the capacity for age-appropriate social relationships with familiar
people and the anxiety must occur in peer settings, not just in interactions with adults.
Anxiety may be expressed by crying, tantrums, freezing, or clinging.
Insight might be absent

PTSD

Reaction to trauma may be expressed instead by disorganized or agitated behavior

Re-experiencing might be seen through play or unrelated to trauma dreams

GAD

Only one physical symptom needed for diagnosis

Insight into condition: waived for children

OCD

OCD in children and adolescents

1/3-1/2 of adults with OCD start presenting
symptoms in adulthood
Pre-pubertal OCD is more common in boys
Pre-pubertal OCD usually associated with tics
Comorbidity common with:

Tic disorders
Anxiety disorders
Disruptive behavior disorders
Learning disorders

Treatment Decision Algorithm Anxiety

Identify anxiety
symptoms
Distress or dysfunction?
Suicidality?

Differential Diagnosis
Other psych dx?
Med cond?
Drug induced?

Physical examination
Baseline labs

Psych or pharm tx for

anxiety?

Pharm
Acute tx with BDZ?
First line agent

Treat comorbidities

Optimize first line agent

8-12 weeks for response

Diagnose specific anxiety

disorder

Non responders
1) Switch to another first
line agent
2) Add combination

Baseline laboratory work

CBC
Fasting glucose
Fasting lipid profile
Electrolytes
Liver enzymes
Serum bilirubin

Serum creatinine
U/A
U/tox
TSH
EKG (>40 years old)
B-hCG
Prolactin

How do we determine what meds to

use?

Drugs used for anxiety can have

FDA approval for that condition
or can be used off-label
Off-label use is based on evidence
based practice

Overview of important medications in

anxiety
SSRIs
Fluoxetine, Paroxetine, Sertraline, Citalopram,
Escitalopram
Can increase nervousness in first few days of
treatment
Cause nausea, insomnia, sexual side effects
Can cause withdrawal (especially paroxetine)
Fluoxetine, fluvoxamine and paroxetine inhibit
hepatic enzymes

Overview of important medications in

anxiety
Serotonin-noradrenaline reuptake inhibitors
Venlafaxine, duloxetine
Side effects: anti-cholinergic
Hypertension, withdrawal symptoms

Tricyclic antidepressants
Amitriptyline, clomipramine, desipramine,
imipramine
Anti-cholinergic, sedation, insomnia, lower blood
pressure, sedation, weight gain
Inhibits hepatic enzymes, toxic in overdose
(cardiotoxic), withdrawal symptoms

Overview of important medications in

anxiety
MAO inhibitors
Phenelzine, Moclobemide
Hypertensive crisis

Mirtazapine
Serotonin receptor 5HT2 and alpha 2 antagonist
Sedation, weight gain

Benzodiazepines
Alprazolam (Xanax), clonazepam (Klonopin),
diazepam (Valium), Lorazepam (Ativan)
Can impair attention and memory, tolerance and
dependence occur

Overview of important medications in

anxiety
Buspirone
5HT1A agonist
Insomnio, nausea

Beta blockers (propranolol, pindolol)

Antihistamines (hydroxyzine- Vistaril, Atarax)
Atypical antipsychotics (risperidone, olanzapine,
quetiapine)
Anticonvulsants (gabapentin, pregabalin,
tiagabin)

FDA approved meds

BDZ- all anxiety dx
Fluoxetine(Prozac)- OCD, PD
Fluvoxamine (Luvox)- OCD
Paroxetine (Paxil)- PD, SAD, OCD, GAD, PTSD
Paxil CR- PD, SAD, GAD
Sertraline (Zoloft)- PD, OCD, PTSD, SAD
Venlafaxine (Effexor XR)- PD, SAD, GAD
Escitalopram (Lexapro)- GAD
Buspirone (Buspar)- GAD
Clomipramine (Anafranil)- OCD

Psychotherapy for anxiety disorders

Evidence based treatments
Cognitive behavioral therapy
! Exposure therapy
! Cognitive modification
Acceptance and commitment based therapy
Yoga and meditation

Treatment modalities children and

adolescents
FDA approved treatments:

Sertraline (Zoloft) for OCD

Fluoxetine (Prozac) for OCD
Clomipramine (Anafranil) for OCD

Evidence-based treatments

SSRIs for all anxiety disorders

Benzodiazepines do not show consistent results in
children
Cognitive Behavioral therapy has shown to be effective
with most anxiety related diagnosis
! Exposure therapy
! Cognitive modification

The development of the UPR Center for Study and Treatment of

Fear and Anxiety

UPR Center for Study

and Treatment of Fear
and Anxiety

Rats

Professional
Training

Healthy humans
Research

Exposure
Therapy
Clinical populations

Translate human findings to the clinic

Increase the use of exposure therapy for anxiety disorders in
Puerto Rico

Community
Outreach

Research on healthy subjects

Model for CS+ response during Conditioning

Actual SCR (S)

1.5

1.0

Factors

Variables chosen for model

Psychological variables entered

stepwise: BAI, STAI, NEO, MSIT,
EST

Conscienciousness
= -0.292 p=0.011

Physiological and demographic

variables entered stepwise:
UCR, SCL, sex, age

UCR = 0.498, p<0.001

SCL = 0.259, p=0.003

0.5

0.0

Adjusted R2 = 0.446**

-0.5
-0.5

0.0

0.5

1.0

1.5

Calculated SCR (S)

Model for CS+ response during Renewal
Factors
Variables chosen for model

Actual SCR (S)

150

100

50

Psychological variables
entered stepwise: BAI,
STAI, NEO, MSIT, EST

Extraversion = -0.360 p= 0.009

Physiological and
demographic variables
entered stepwise: UCR,
SCL, sex, age

Sex = 0.330 p= 0.016

0
0

20

40

60

80

100

120

140

Adjusted R2 = 0.242**

Calculated SCR (S)

Martinez el al., BMAD, 2012

Puerto Rican Males have higher SCR

Females Females
MA
PR

Males
MA

Males
PR

Martinez el al., Plos One, 2014

Current projects
Genetics of fear conditioning and extinction
The role of propranolol on fear learning and
extinction
Fear conditioning and extinction in anxiety
disorders
Effect of ataque de nervios on anxiety disorder
Cultural adaptation of evidence based treatments
for Puerto Ricans with anxiety disorders

Centro para el estudio y tratamiento del miedo y la ansiedad

de la Universidad de Puerto Rico
787-758-2525 ext 3431
[email protected]