Anxiety Disorders Flashcards
1
Q
what is Clinical Acute Stress reaction from a clinical perspective?
- symptoms
A
- a response to an exceptionally stressful event (physical/ psychological)
- this can last hours up to 3 days
- presents with an initial daze, individual vulnerability with a mixed and changing picture
- numb or dazed feeling
- Insomnia
- restlessness
- poor concentration
- autonomic aurosal
- anger/anxiety depression
- withdrawal
2
Q
What is adjustment disorder?
A
- An adverse reaction in an individual unable to cope with stressful life changes.
- the stressor is not necessarily life-threatening
- presents with a wide range of emotional or behavioural symptoms
- out of proportion to the stressor
- can last up to 6 months
3
Q
What is PTSD?
A
- response to an exceptionally threatening or catastrophic event
- could be experienced or witnessed that involved actual or threatened death or serious injury or threat to the physical integrity of self or others
- the response involved intense fear helplessness or horror
- Usually immediate onset - most recover within 1 year
- Rape victims
- 94% at 2 weeks
- 65% 1 month
- 42% at 6 months
4
Q
PTSD Symptoms
A
- Re-experienceing flashbacks/ nightmares
- Numbness/ detachment
- Avoidance
- Hypervigilance/startle
- Insomnia
- Anxiety/depression
5
Q
What is Generalised Anxiety Disorder from a clinical perspective? (GAD)
- characteristic features
A
- persistant symptoms of anxiety that are not restricted to or strongly predominating in any particular set of circumstances
Characteristic features
- worry and apprehension
- headache & motor tension
- restless/ trembling
- autonomic hyperactivity
- sweating/ palpitations
- dry mouth
- epigastric discomfort discomfort
- dizziness
6
Q
What are the psychological symptoms of GAD?
A
- fearful anticipation
- Irritability
- Sensitivity to noise
- Restlessness
- Poor concentration
- Worrying thoughts
- Sleep disturbances: Insomnia, night terrors
- Sadness
- Depersonalisation
- Fixation with details
7
Q
Give an overview of the epidemiology of GAD
A
- greater prevalence in women than men
- ~3x higher in patients in primary care clinics
- high level of co-morbidity (~70%)
- especially simple phobias, social phobia, panic disorder & depression
8
Q
Aetiology of GAD
A
- Genetic factors play a moderate role in the prevalence of GAD
- the experience of one very important unexpected negative event was associated with 3x increase in GAD in men and women
- Disruption in early attachment forming can lead to withdrawal and depression
- a healthy parent-child relationship fosters a sense of control over events
- lack of warmth and encouragement leads to a general perception of personal inefficacy which may predispose to negative states
- overprotective coupled with a lack of warmth and responsiveness toward the child could lead to anxiety
9
Q
What are the clinical features of Panic Disorder?
A
Psychic
- Fear of losing control, going mad fainting, dying, derealisation, depersonalisation
Somatic
- Palpitations, tachycardia, sweating, trembling
- dyspnoea, choking, nausea, ‘butterflies’
- chest pain, urgency, dizziness, faintness, paraesthesia, chills/flushes
10
Q
What are the potential differential instead of Panic Disorder?
A
- Endocrine
- Hypoglycaemia
- Phaeocromocytoma
- Carcinoid
- Cardiovascular
- Arrythmia
- Respiratory
- Asthma
- Drugs
- Neurological
- Seizures
- Vestibular
11
Q
What is Agoraphobia from a clinical perspective?
A
- Anxiety in a specific context
- away from home
- in crowds
- in situations, they cannot easily leave
- Presents with anxiety symptoms & panic attacks
- anxious cognitions about fainting and loss of control are common
- Avoidance is common
12
Q
Describe the genetic and environmental aetiology of Panic Genetic Predisposition
A
- increased risk in 1st degree relatives (7x)
- increased concordance in monozygotic twins
- modest inheritability suggested by family & twin studies
- at least 50% environmental influences
- seperation/loss
- relationship difficulties/ new relationships
- Traumatic early life events
- early parental seperation
- traumatic childhood event - 3 fold)
- early sexual abuse (<5 years of age)
13
Q
Describe the biological aetiology of Panic disorder
A
- panic attacks triggered in the locus coeruleus
- increased firing associated with increased CO2 etc
- Noradrenergic agents - yohimbine & isoproterenol - stimulate attacks in sufferers
- SSRIs are effective but contradictory findings regarding the role of serotonin
- y-Aminobuyeric acid (GABA) plays a role
- Benzodiazepine agonists are effective’
- Benzodiazepine antagonists (flumazenil) aggravate attacks
- CCK causes panic attacks in animals & pentagastrin causes attacks in panic disorder patients
14
Q
Explain the Genetic Aetiology of Specific Phobias
A
- all specific phobias have evidence of for genetic transmission
- 31% of 1st degree relatives are affected
- Animal phobias
- monozygotic -26%
- Dizygotic 11%
15
Q
Give psychological theories of the aetiology of Specific Phobias
A
- Psychoanalytic approach: Symptoms related to unresolved unconscious conflicts
- Classical conditioning: phobias are learned through the association of negative experience with an object or situation
- Marks’ ‘preparedness’ theory: maintains that commonly feared objects are those that historically threatened the survival of the individual or the species
Large number of studies suggest that phobias may be acquired via observational learning
16
Q
What are the symptoms of Social Phobia?
A
- Anticipatory anxiety
- Feeling anxious
- Blushing
- Trembling (observed writing is a problem)
- Relieved by alcohol (potential for abuse)
17
Q
Explain the aetiology of social phobia
A
- genetic factors contribute <1/3 of the variance in the transmission
- monozygotic inheritance is more prevalent than dizygotic
18
Q
Explain OCD
A
- imbalance between direct and indirect pathways through the basal ganglia
- Obsessional thoughts / images
- Words, ideas, beliefs and/or images
- Recognised as own
- Intrude forcibly into the mind
- They are resisted
- Compulsions reduce anxiety
- Cleaning/checking
- Precision – ‘just right’
19
Q
Explain the epidemiology of OCD
A
- prevelance in women = men
- some studies suggest a slight female predominance
- During adolescence, boys > girls
- The mean age of onset is ~ 20 yrs of age
- Prevalence is 2-3% of population
- can be environmental: Streptococcal infection
20
Q
What co-morbidities exist with OCD?
A
- Major depressive episode: ~67% lifetime prevalence
- ↑ lifetime risk for:
- alcohol disorders
- social phobia/ specific phobia
- panic disorder
- eating disorders
- Schizophrenia
- tic disorders (~ 40% in juvenile OCD)
- ↑ prevalence of Tourette’s syndrome in relatives
- Unclear relationship between OCD & obsessive-compulsive personality disorder (OCPD), but it appears that OCPD is not a prominent risk factor for OCD
21
Q
Genetic Aetiology of OCD
A
- the monozygotic transference is much greater than the dizygotic prevalence
- first-degree relatives of patients with childhood-onset OCD have a higher than expected incidence of OCD
- common underlying genotype for Tourette’s and OCD
22
Q
Review this picture and how Amygdala plays a role in emotion
- effect of lesions in the amygdala
A
- HPA: Hypothalamus-pituitary- adrenal axis
- lesions in the amygdala can cause loss of fear
23
Q
Which key areas from this overview of how the amygdala emotional activity causes fear
A
key areas affected are the
- lateral hypothalamus –> sympathetic activation –> tachycardia, galvanic skin response, paleness, pupil dilation, blood pressure elevation
- ventral tegmental area/ locus coerulus/ dorsal lateral tegmental nucleus –> activation of DA, NE and ACh –>behavioural and EEG arousal, increased vigilance
- periventricular nucleus –> ACTH release –> corticosteroid release (stress response)
24
Q
How does fearful stimuli elicit a stress response?
A
- sensory info channelled to the amygdala
- amygdala excites locus coeruleus (LC) + hypothalamus –> acute stress response
- HPA axis s also activated
- H releases CRH: corticotropin-releasing hormone
- P releases ACTH: adrenocorticotropin hormone
- A releases cortisol
- LC releases NE, which triggered “fight or flight” response
- HPA axis s also activated
25
Explain the Push-pull regulation of the HPA axis
* Amygdala stimulates the HPA axis which releases cortisol
* the Hippocampus inhibits the activity of the HPA axis, less cortisol is released
* cortisol acts as positive feedback to increase the dysregulation activity the hippocampus has on the HPA
26
Explain the neurobiology of chronic stress and how some anxiety orders may be caused as a result
* Chronic activation of glucocorticoid receptors in hippocampus leads to
* increased Ca2+ entry into neurons
* too much Ca2+ - excitotoxic - cells die
* _hippocampus can’t feedback to limit cortisol production_
* Thus some anxiety disorders may result from:
* diminished activity of hippocampus
* loss of feedback to the amygdala
* inappropriate fear responding
_(evidence - hippocampal volume in PTSD patients reduced)_
27
What is the effect of stress on the brain?
* causes cell death in the hippocampus
* loss of pyramidal cells
28
What is the treatment for anxiety disorder?
* **Benzodiazpines**, partial agonists of the GABAa receptor, anxiolytic
* work well in: GAD and PD
* not effective in: OCD and PTSD
* **SSRI** (serotonin selective reuptake inhibitors)
* work well in: OCD, PTSD, PD, GAD
* can be anxiogenic in short term, but anxiolytic effects may not become apparent for weeks
* **Busperine** ( 5-HT1A receptor partial agonist)
* works for GAD (4-6 weeks to see the therapeutic effect)
* **Cognitive Behavioural Therapy**
29
What is the overall concept when approaching how to treat anxiety disorders?
* **Drugs increasing GABA activity reduce anxiety (anxiolytic)**
* ****partial agonist: Alcohol
* indirect agonist: Barbiturates, Benzodiazepines
* **Drugs decreasing GABA activity increase anxiety (anxiogenic)**
* ****Benzodiazepine antagonist: Flumazenil
## Footnote
**_They all act at the GABA(A) ionotropic receptor_**
30
What does this scan suggest about GABAergic dysfunction in anxiety disorders?
* Patients with PD have fewer benzodiazepine binding sites
* (it was radiolabeled with Flumazenil - which also indicates BSD binding sites)
* therefore this suggests PD patients lack sufficient inhibitory control in cortical and limbic regions to prevent inappropriate fear responses and subsequent panic attakcs
31
What role does the serotonergic system play in anxiety?
* SSRIs used in treatment (*Fluoxetine/ Prozac*)
* prolong the action of 5-HT in the synapse
* Buspirone
* also acts as a partial agonist
* works on somatodendritic 5-HT receptors
* symptomatic changes are seen after weeks of treatment
32
How does antidepressant treatment affect neuroplasticity?
* produces an overall trophic effect due to increased BDNF gene expression
* increased 5-HT and NE availability at receptors
* leads to increased Adenylate cyclase and increased Ca2+ dependant kinases
* increased AC --\> increased cAMP --\> increased c-AMP dependent kinase
* increased kinase activity --\> increased CREB activity which increases gene expression
* reversal of stress-induced changes may restore normal brain function (hence several weeks until symptomatic changes are seen)
33
How do the serotonergic systems and the norepinephrine systems relate to panic disorder?
* Serotonergic systems and Norepinephrine systems project diffusely through the brain and are thought to have opposing functions.
* NE release stimulates arousal and alertness
* 5-HT inhibits Norepinephrine (NE) release
* Opposing functions in various brain areas
* amygdala
* hippocampus
* hypothalamus
* A shifted balance between the pathways to NE may be manifested in Panic Attacks - fear responses to inappropriate stimuli
* SSRIs, by increasing 5-HT release, will push balance back
34
The Indirect and Direct pathways and its relation to OCD
* D1- direct pathway that facilitates movement (red)
* controls previously learned behaviour so they become automatic and can be executed
* D2- indirect pathway that inhibits movement (black)
* suppresses these behaviours allowing the person to switch to more adaptive behaviour (behavioural flexibility)
* overactivity of the direct pathway may lead to the compulsive behaviours without being able to switch them off
* GPe = external segment of the globus pallidus;
* GPi = internal segment of the globus pallidus;
* SNc = substantia nigra pars compacta;
* STN = subthalamic nucleus.
35
What is the best treatment for OCD?
* Benzodiazepines
* good immediate effect but patients can develop tolerance --\> potential abuse and anxiety during withdrawal
* SSRI
* *fluoxetine*
* can initially act as an anxiogenic
* *Clomipramine*
* a tricyclic antidepressant (TCA)
best to combine BZD and SSRI and taper of BZD when tolerance starts to build and the SSRI starts taking effect
36
How does caudate hyperactivity relate to OCD?
* The caudate sends GABAergic inhibitory projections to the globus pallidus (GP),
* which sends inhibitory projections to the thalamus,
* which then projects to the OFC.
* It’s possible that OCD involves disinhibition which leads to activity reverberating in this circuit.
after pharmaco- and psychotherapy interventions in OCD PET scans show decreased caudate activity
37
What other areas in the brain play a role in the pathophysiology of OCD?
* **OCD pathophysiology mainly dysfunction of the fronto-striato-thalamic circuit routing through the orbitofrontal cortex**
* underactivation of the OFC
