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 top-down 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 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.
Panic 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 7 minutes and then slowly 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.
Panic disorder
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 was calm but then he 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.
Specific Phobia
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 choking, sweating and nausea. He says that he 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.
Social Anxiety Disorder
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 Avoidant, schizoid
Paranoia Depression Autism spectrum disorder Pragmatic communication disorder Oppositional defiant disorder
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 has been feeling restless, tired and irritable. He has had difficulty concentrating and sleeping as well as muscle tension.
Generalized Anxiety
Disorder
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 complains of pain when his father has to go to work on Saturday. 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
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 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.
Obsessive compulsive
disorder
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 MRI-pointing 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 ambush. He also avoids leaving his house 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.
Post-traumatic stress disorder
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 unable to sleep in the past three months because of recurrent nightmares about an ambush. He also avoids leaving his house 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.
Exposure to actual or threatened death, serious injury or sexual violence One or more
intrusion symptoms
Avoidance of stimuli associated with
trauma
Negative alterations in cognitions and mood
associated with trauma
Two or more symptoms of altered
arousal/reactivity
PTSD specifiers time
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-pituitary-adrenal axis
Effect of cortisol on development of amygdala and hippocampus Reduced hipoccampal
volume in adults
MD2017
MD2017
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
MD2017
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
OCD Insight into condition: waived for children
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
Diagnose specific anxiety disorder
Treat comorbidities
Psych or pharm tx for anxiety?
Pharm Acute tx with BDZ?
First line agent
Optimize first line agent 8-12 weeks for response
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
Translate human findings to the clinic Increase the use of exposure therapy for anxiety disorders in
Puerto Rico
UPR Center for Study and Treatment of Fear
and Anxiety
Research Exposure Therapy
Professional Training
Rats Healthy humans
Clinical populations
Community Outreach
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Act
ual S
CR
(S
)
Calculated SCR (S)
Model for CS+ response during Conditioning
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
Puerto Rican Males have higher SCR
Females MA
Females 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]
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