Phobias & SAD and GAD & PD

- genetic component: higher risk among first-degree relatives (Fyer et al. 1990)

- mixed results regarding genetic vs. environmental contribution (Bolton et al. 2006)

- genetic contribution varies to subtype – more specific genetic contribution for

blood phobia (Fyer et al. 1990)

- neuropathophysiology remains poorly understood (Fyer et al. 1998)

mixed results about amygdala hyperactivation as in other anxiety disorders

(Gossens et al. 2007)

cognitions play a role in maintainance (Rachmann 1991)

- cognitions increase arousal and likelihood of escape or avoidance (Last 1987)

empirical support:

- exposition to feared situation lead to triggering of negative self-statements, which

heighten physiological activity (Last and Blanchard 1982)

- most patients report at least one unrealistic belief about the harm that could befall

them when confronted with object or situation (Thorbe and Salkovskis 1995)

- attentional bias toward phobia related threats (Burgees 1982, Mogg et al.2004)

- Stroop paradigm: phobic individuals are slower to name the color of threat related

words (Constantine et al, 2001)

More effective than insight-oriented group or individual psychotherapy (Gelder et al. 1967)

Four approaches:

Flooding

In vivo exposure

Modeling

Systematic desensitization (Wolpe 1958)

• Gradual

• Prolongued exposure -> psychoeducation

• Therapist needs to be comfortable with phobic object

• Eye movement desensitization and Reprocessing

• Hypnotherapy: several studies reported success of hypnosis in phobia treatment

(Bird 1997, Ginsberg 1993, Morgan 2001)

-> group studies no comparison group (Peretz et al. 1996), many dropouts

(Hamarstrand et al. 1995)

• Psychopharmacology:

not treatment of choice for specific phobia (Roy-Byrne and Cowley, 2007)

studies using benzodiazepines showed no evidence of

long-term reductions in anxiety or avoidance (Campos et al. 1984)

based on preliminary studies

• Blood-Injection-Injury phobia: treatment complicated by fainting

applied tension-> tensing various muscle group during exposure

• One of the most common psychological disorders

• Lifetime prevalence rates for SAD based on large community samples range

from 3 to 13% (Kessler et al., 2005)

• Tends to begin in adolescence (mid / late teens) but also earlier possible

• Mean onset 15.7 years (Brown et al. 2001) -> lower compared to other AD

• Onset later in adulthood are rare and may be secondary to another mental disorder

(social withdrawal MDD, avoidance of eating in public)

• SAD slightly more common in women than men (Fehm et al., 2005)

• Gender differences in presentation of SAD (Turk et al. 1998)

women: talking to people of authority, performing in front of audience, working while

being observed, entering a room where others are already seated, being center

of attention, expressing disagreement, throwing a party

men: returning goods to a store, urinating in a public bathroom

• People with SAD are invested in making a positive impression on others, but

are insecure about ability to do so

• They hold negative beliefs about themselves and their ability to perform in social

situations

• When in social situations people with SAD focus on themselves and see

themselves as if they’re watching themselves on television

• Focusing on themselves doesn’t allow people with SAD to fully participate

in the social situation

• People with SAD either avoid situations of use safety behaviors in feared

situations

• Safety behaviors and avoidance do not allow the person to learn that fears

may not actually come true

• Negative thinking about social situations occurs before, during and after

exposure to the situation

• Source of perceived threat for people with SAD is the belief that others hold

unreasonable high expectations of them, “reaction of an audience”

• audience reaction ->mental representation

• Mental representation is influenced by self-image from memory, pictures, physical

symptoms and social feedback

• Mental representation often distorted: people with SAD rate their performance as

poor, even if not objectively true

• Feedback often distorted or twisted to be consistent with fears

• People with SAD report a history of childhood teasing more often than people without

SAD (Mc Cabe et al. 2003)

• Severe bullying during childhood related to higher frequency of SAD

(Gladstone et al., 2006)

• Lacking social experiences (socially anxious individuals often raised by socially

isolated parents (Bögels et al. 2001)

• Observational studies: parents of anxious children support more likely desire of

child to be avoidant (Dadds et al. 1996)

• However, negative learning cannot fully explain how SAD develops

• Studies comparing CBT to other psychotherapies for SAD, CBT superior

(Rodebaugh et al.2004)

• The most frequently studied, evidence based psychological strategies for SAD

include:

- cognitive strategies (identifying anxiety provoking thoughts, replace such thoughts with

more realistic thoughts and predictions, behavioral experiments to test validity of anxious

thoughts)

- exposure-based-strategies

- social skills training (improve social and communication skills, eye contact, body language,

making small talk..)

• Mixed results: combination of exposure plus cognitive therapy works better than

exposure alone. Other studies found exposure alone just as effective (Rodebaugh et al.,2004)

• In addition some studies suggest that applied relaxation (PMR combined with

exposure) is also useful (Rodebaugh et al. 2004)

• Social skills training has been shown to improve effectiveness of CBT, other studies

found no difference between CBT with or without social training (Rodebaugh et al. 2004)

• Considerable evidence supporting SSRIs as first-line pharmacological treatment

for SAD, with proposed length of treatment for 6-12 months

• No consistent evidence that combining CBT and medication leads to better outcomes

than either treatment alone (Davidson et al. 2004)

• Relapse rates higher following discontinuation of pharmacotherapy than

discontinuation CBT (Liebowith et al., 1999)

• Biological factors:

Genetic factors:

- Genetic predisposition

- Family and twin studies indicate that genetic factors account for 30-40% of the variance of

causative factors

• Neurotransmitter systems:

consistent Norepinephrine overactivity in GAD

alterations in GABA, serotonin system

• Fear circuit:

components of the fear circuit that may be of particular relevance to GAD include medial

prefrontal cortex, amygdala, insular cortex

- irregularities in the functioning of the amygdala in GAD patients and its connection

to the prefrontal cortex (Etkin et al., 2009)

Worry as cognitive avoidance Borkovec et al. 1994, 2004

• Worry has an important function for people with GAD

helps people avoid experiencing negative emotions

• Does not allow deeper emotional processing

• Worry is thought to be a linguistic process that does not tap into deeper mental

images

• People can avoid negative emotions associated with the worry is processed

without mental imagery

• Studies

people who were worrying did not create imagery; rather worry was experienced

as negative verbal/linguistic activity (e.g. Borkovec&Inz, 1990)

people verbally articulating fear material created much less heart rate activity

than when imagining the situation (Vrana et al.1986)

verbal processing impedes environmental and experiential information from being

process, preventing learning of nonthreatening associations (e.g. Roemer &

Orsillio, 2002)

• Worry can help someone anticipate and plan for the future

• For people with GAD worry helps

- avoid or prevent bad events

People with GAD find it more difficult to tolerate and accept uncertainty than

people without GAD (Dugas et al. 1998)

- motivate oneself to get things done

- prepare for the worst

- problem-solve

- distract oneself from even more emotional topics

- and superstitiously lessen the likelihood of bad events

• Processing bias to threat plays an important role in development and maintenance of anxiety

(Mogg & Bradley, 2005)

• attention bias: for threatening words and pictures

Person with GAD hypervigilant in detecting particular threats, leading to worry

• Interpretation bias: interpreting ambiguous stimuli as threatening

(e.g viewing news->personal threat)

• People with GAD display both biases (Mogg & Bradley, 2005)

• worry about worry

• For people with GAD often belief that worry is associated with going crazy or

uncontrollability of worry

->start to worry about how much they are worrying

• Metaworry good discriminator between GAD and other anxiety disorders

• During CBT therapists attempt to reduce low level of processing by having patients

“worry out “ their negative emotions -> exposure therapy to help processing worry

on a deeper level

• Although GAD mostly characterized by cognitive avoidance, behavioral avoidance

of situations (e.g. social situations) is seen in over half of the individuals

(Butler et al. 1987)

• CBT helps to reevaluate:

- the positive benefits of worrying

- interpretation biases of ambiguous stimuli

- their intolerance of uncertainty

- metaworry

• Most frequently studied, evidence-based, psychological strategies for treating GAD

include:

- Cognitive strategies

- Exposure-based strategies

- Acceptance based strategies

• CBT has been shown to be very effective for the treatment of GAD, with long term

effects

• Clinical improvement in 38-63% of individuals who complete treatment

(Waters & Craske, 2005)

-> this number not as high as CBT for other anxiety disorders

(80% clinical improvement in panic disorder, Campbell & Brown, 2002)

• Adding of mindfulness components leads to improvement of existing CBT treatments,

clinical improvement in 78% of individuals (Roemer et al.2008)

• Evidence for pharmacological treatments:

large randomized placebo-controlled trials with GAD have been conducted with

Benzodiazepines and antidepressants

• Compared to placebo, benzodiazepines provide effective and rapid symptomatic relief

(Galenberg et al. 2000)

-> should not be used for more than 2-4 weeks

-> side effects: dependency, sedation and increased risks of neonatal and infant mortility when

used while breastfeeding or late pregnancy

• SSRI are the recommended treatment

-> pharmacological treatments reduce physical symptoms rather than worry

(Anderson & Palm, 2006)

-> works also for co-morbidities

-> long term efficacy of antidepressant with follow-up of years required

->efficacy over 6 months follow-up periods: greater remission rates than placebo at 6 months

(69% vs. 42-46%)

• Very few studies compared effectiveness CBT with medication treatments for GAD

• Redmond (1981): stimulation locus coeruleus produced fear response in

monkeys

• Efferent axons of locus coeruleus that project to the hypothalamus are of

special significance for panic disorder (Charney & Heiniger, 1986)-

>influence on HPA-axis

• Administration of the noradrenergic antagonist yohimbine produced panic

attacks in panic disorder ( Abelson et al. 1992)

• Dysregulation (hyperactive) of noradrenergic system in panic disorder

(Coplan et al., 1997)

• Desynchronization of noradrenergic system and HPA axis possible but not

completely successful (Coplan et al. 1995)

• Dysfunctional neurotransmission at the serotonin receptors (5HT1A) may result in

anxiety or avoidant behavior (Deakin 1996)

• Activation of HPA Axis in panic disorder, may contribute to disruption of

hippocampal 5HT1A

neurotransmission (Lesch and Lerer 1991)

• Aberrant noradrenergic- serotonergic function (Boyer 1995)

• Serotonin depletion resulted in increased minute ventilation in panic disorder

patients

unaltered ventilatory function in controls (Kent et al., 1996)

• GABA = inhibitory neurotransmitter

• Benzodiazepines increase function of GABA

• global decrease in benzodiazepine binding

• with a peak decrease in orbitofrontal cortex, and insula, hippocampus in panic

disorder patients compared to healthy controls (Malzia et al., 1998)

• Injection of sodium lactate (panicogen) led to panic-like response in

GABA-blocked rats only (Shekhar 2006)

• Interaction GABA-glutamate interrupted in panic disorder

= substances that can induce panic attacks

• substances that influence HPA Axis

Yohimbine (noradrenaline increase)

coffein: adenosinergic (inhibitory) receptor antagonist

• Substances that influence lactate metabolism

sodium lactate, sodium bicarbonate, carbon dioxide

• Twin studies have attributed 30-40% of the variance for the liability to develop

panic disorder to genetic factors (Kendler et al., 2001; Scherrer et al. 2000)

• highly significant association between panic disorder in probands

and first degree relatives (Hettema et al. 2001)

• cholecystokinin, adenosine 2A, MAO A, and COMT genes.

• Dynamic Model:

panic attack = expression of an intense unconscious conflict (Bush et al. 1999)

core conflict of depencency and inadequacy (Shear et al. 1993)

Contemporary dynamic models: integration of biological and developmental stressors

(Milrod et al. 2004)

• Cognitive Behavioral Models

• Anxiety Sensitivity

• Core fear toward anxiety and its associated somatic symptoms

• Measured by anxiety sensitivity index

(Reiss et al. 1986)

• Significant predictor of the onset of panic in different patient populations

(e.g Ehlers 1995, Hayward et al. 2000; Maller and Reiss 1992)

• Ley (1985): hyperventilation theory : hyperventilation causes panic attacks

• Klein (1993): false suffocation alarm model: hyperventilation avoid panic

attacks

Person is hypersensitive to carbon dioxide levels ⇒ Minor drops in Oxygen result in false alarm "person is suffocating" ⇒ Panic Attack

First line treatments

• SSRI (Selective Serotonin Reuptake Inhibitors)

effective in many controlled studies ( e.g. Wade et al. 1997; Michelson et al 1998, 2000)

anxiolytic effect latency of 2-4 weeks

• Serotonin Norepinephrine Reuptake Inhibitors

effective in double blind placebo controlled studies (Bradwejn et al. 2005; Pollack et al. 1996)

Second line treatments

• Tricyclic antidepressants

frequency of adverse events is higher than for SSRI (Amore et al. 1999)

Third line treatments

• Benzodiazepines

anxiolytic effects immediately after oral intake, risk of dependency (Bradwejn 1993)

Cognitive behavioral therapy

“Panic control treatment”

(PCT, Craske et al., 2000, Hofmann & Spiegel, 1999)

Elements

• Education about anxiety and panic development

• Cognitive restructuration: identification and correction of thoughts /

false cognitions about anxiety and its consequences

• Training (reduction arousal, hyperventilation)

• Exposition, controlled hyperventilation

11-12 sessions, 3-4 months

Classical CBT Methods

• Hyperventilation

• Triggering bodily symptoms

• Deep breathing

• External focus

• mindfulness

Interoceptive exposure

Feared sensations become safe sensations:

• in the office with the therapist

• at home

• independent of the treatment context

Panic Cycle

Uh oh!

What if:

• This gets worse?

• I lose control?

• This is a stroke?

I have to control

this!

Relative Comfort

• Notice the sensation

• Do nothing to control it.

• Relax WITH

the sensation

Head rolling – 30 seconds - dizziness, disorientation

Hyperventilation – 1 minute - produces dizziness

lightheadedness, numbness, tingling, hot flushes, visual

distortion

Stair running – a few flights – produces breathlessness, a

pounding heart, heavy legs, trembling

Full body tension – 1 minute – produces trembling, heavy

muscles, numbness

Chair spinning – several times around – produces strong

dizziness, disorientation

Mirror (or hand) staring – 1 minute – produces derealization

• Efficacy between 87% and 75%

• Greater efficacy than relaxation therapy or control groups

• Greater efficacy than certain medicaments (e.g. alprazolam) and

similar to imipramine

• Long-term treatment with PCT is more effective than pharmacological

treatment

• Evidence of superiority from combined approach towards single treatment

not conclusive

• New developments: combination with self-help modules, therapy via

internet, electronic auto-observation