GAD Flashcards
What structures make up the lambic system?
Hippocampus
Amygdala
Thalamus
Hypothalamus
Cingulate gyrus
Define GAD…
A condition of stress/anxiety that is persistent, excessive and disproportionate/unrealistic
Which area of the brain integrates the emotional response from the limbic system into the process of decision making?
The prefrontal cortex
Which area of the brain is overactive in GAD?
The amygdala
How does GABA relate to GAD?
A reduction of GABA causes decreased inhibition to the Amygdala
This causes overactive amygdala, releasing more stress hormones/increased fear response
= disproportionate/unnecessary anxiety
What is the pathophysiology of GAD?
Dysregulation (decrease) in GABA-A secretion
This causes reduced inhibition on the amygdala
Causes amygdala to become over active
Generates a disproportionate/unnecessary stress and fear response
Which neurotransmitter is associated with GAD?
GABA-A
What is the increased risk of GAD if a first degree relative has GAD?
2.5x increased risk
What factors cause an increased chance of GAD?
Genetic:
- first degree relative has GAD
- mutations in the chromosomes: 2p21 and 2q12
Environmental:
- childhood trauma (parental neglect or over-control)
- major distressing life events
What must the symptoms cause in order to be diagnosed with GAD?
Significant distress
Impairment of daily functioning
What are the DSM5 criteria for a diagnosis of GAD?
- Persistent fear and worry
- Plus at least 3 of:
- poor concentration
- restlessness
- fatigue
- muscle tension
- initial insomnia (difficulty getting to sleep)
Symptoms must be prevalent for 6+ months
How long must symptoms have persisted for in order to diagnose GAD?
6+ months
What are 3 other conditions that could be misdiagnosed as GAD?
- Alcohol/drug misuse
- Hypothyroidism
- Phaecochromocytoma (adrenal gland cancer)
What are some psychological symptoms of GAD?
- constant worries/intrusive thoughts
- feelings of apprehension and dread
- poor concentration
- depersonalisation, derealisation (if severe GAD)
What are some physical symptoms of GAD?
- tremors, butterflies, palpitations
- sweating
- dry mouth
- muscle tension, tension headaches
- hyperventilation (difficulty taking breath, stabbing chest pain, parasthesia)
What are the features of hyperventilation?
- difficulty taking a breath
- “atypical” chest pain = stabbing, non radiating, not central (usually on left)
- parasthesia in hands, feet, lips
- respiratory acidosis
What are some behavioural symptoms of GAD?
- putting things off because of anxiety
- avoiding particular situations
- self medication to relieve anxiety (alcohol, drugs)
What is the epidemiology of GAD?
- Almost 2x more common in women
- median onset age = 30
- most common diagnosis in young adult life
- most commonly recognised due to physical symptom presentation
What is the most common mammalian structure of the GABA-A receptor?
Subunits:
2x alpha-1
2x beta-2
1x gamma-2
Chloride ion in middle
Describe the (chemical) synthesis of GABA?
Glutamate (Glutamic acid) => decarboxylase => GABA
How is GABA removed from the synapse?
Re-uptake into PRE-SYNAPTIC terminal and surrounding GLIAL CELLS
What are the 2 classes of GABA receptors?
GABA-A
GABA-B
How does GABA binding to GABA-A receptors cause hyperpolarisation (inhibition)?
GABA-A receptor structure = 5 subunits surrounding a chloride ion
- GABA binds to receptor
- activating chloride ions to travel through into neurone
- decreases charge inside neurone = hyperpolarisation
What are the main treatment options for GAD?
- medication (diazepam, pregabalin, SSRIs, SNRIs, TCAs)
- psycho therapies (CBT, counselling, group therapy)
- lifestyle changes (exercise, avoiding caffeine/alcohol etc)
What is the maximum amount of time a person can be on benzodiazapines for?
No longer than 2 weeks
(They are very addictive)
How long does NICE recommend a course of CBT should be for GAD?
12-15 hour long sessions over 4 months
What % of GAD patients respond well to CBT?
60%
Compare medication Vs CBT in efficacy of treating GAD?
Both have similarly high efficacy!
Recommended to use both for best results
Means treatment route is a patient decision as both are effective methods
What is the action do benzodiazepines in GAD?
Positive allosteric modulator of GABA-A receptor = INCREASES GABA ACTION
Binds to allosteric site on GABA-A
UP-regulates GABA action
= increases chloride transmission
= restores inhibitory action of GABA
What is the first-line pharmacological treatment for GAD? Why?
SSRIs
- not addictive
- fewer side effects
- safer in overdose
Describe what a course of SSRIs would entail?
- effective after 1-2 weeks of use
- continue for at least 6 MONTHS if effective
- mild withdrawals = TAIL OFF at end of course
What are the side effects of SSRIs?
- nausea, diarrhoea
- sexual dysfunction
- dry mouth
- dizziness
- loss of appetite
- insomnia
In what’s % of GAD cases are SSRIs effective?
70%
What other conditions can be treated by Pregabalin?
- Epilepsy
- Neuropathic pain
Pregabalin = anticonvulsant
What is the MOA of pregabalin?
- Decreases release of glutamate, Substance P and NA (excitatory)
- Similar structure to GABA
Specific action is unknown
What is the main difference between each benzodiazepine drug?
The length of their half life
- diazepam = 30 hours
- triazolam = 2 hours
How quickly do the effects of benzodiazepines kick in in GAD?
Within 30-60 mins
What are side effects of benzodiazepines?
- addiction/dependence (withdrawal can include seizures)
- tolerance
- sedation
- impaired cognition
What are Beta-Blockers effective at treating in GAD?
PHYSICAL symptoms (tremors, sweating…)
Not psychological
What is the MOA of beta-blockers?
Beta-adrenergic ANTAGONISTS on smooth muscle (heart…)
Name one condition that beta-blockers are contraindicated in?
Asthma
What is agoraphobia?
Fear of crowded places
