Generalised Anxiety Disorder Flashcards
Neurobiology
The prefrontal cortex uses logical thought to reduce anxiety → process disrupted.
The anterior cingulate cortex amplifies negative information, increasing anxiety → can be beneficial in identifying dangerous situations but there is hyperactivity in GED.
The amygdala of the limbic system inhibits the PFC and initiates the fight or flight response → PFC-amygdala connectivity is disrupted in anxiety disorders, resulting in hyperactivity.
Genetics
30% heritability if one parent has GAD.
Mutations are linked to monoamine neurotransmission and neurotrophic signalling.
Risk genes include:
* SERT short allele
* 5-HT1A receptor polymorphism causing increased negative feedback so decreased serotonergic signalling
* MAO-A polymorphisms causing increased monoamine metabolism and so decreased signalling.
* BDNF polymorphisms resulting in reduced activity
Neurotransmitters
GABA-A receptor is downregulated, so symptoms are treated with agonists.
SSRIs have been shown to improve symptoms, suggesting that 5-HT is involved.
Patients are hypersensitive to cholecystokinin (CCK) agonists, so there have been trials investigating CCK-antagonists → unsuccessful.
CRH and HPA-axis dysfunction thought to be involved → negative feedback is impaired.
Treatment
Autonomic symptoms on the heart are treated with β-AR antagonists, e.g. propranolol.
SSRIs - sertraline
SNRIs - duloxetine
Atypical antidepressants - mirtazapine, vilazodone - broader spectrum
Benzodiazapines: diazepam
Used in anxiety treatment short-term in a crisis when there is a high risk of suicide.
Enhance GABA action by binding to GABA-A receptors and acting as PAMs.
Increase likelihood or duration of channel opening.
This increases Cl- influx, causing hyperpolarization and so reducing neuronal activity.
Novel treatment targets
Glutamatergics - ketamine, riluzole, xenon
Neurosteroids - aloradine
Cannabinoids
MDMA (ecstasy)
L-Dopa
