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

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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 Karen.martinez4@upr.edu