PED3008 L7 Stress Aetiology and Pathology

Fear learning

with cortices and hippocampus the amygdala

• associates stimuli with consequences of experience (fear) = acquisition

• stores memories of fear-evoking stimuli

the amygdala appraises new stimulus

places it in the context of stored emotional memories

effect of CRF on behaviour

• CRF in LC and cerebral aqueduct increases spontaneous activity, indicating arousal and agitation

• CRF in cerebral aqueduct increases locomotor activity

• high level CRF in aqueduct inhibits spontaneous activity and locomotor activity - indicating freezing

negative feedback in the endocrine stress response

• glucocorticoid receptors

• mineralocorticoid receptors

endocrine dysfunction in anxiety disorders

• some PTSD studies have shown decreased urinary cortisol levels

• some have shown no changes in urinary cortisol in women

PTSD hypothesis (Yehuda) increases glucocorticoid feedback sensitivity

• enhanced response to low dose dexamethasone suppression test

• increased glucocorticoid receptor density (lymphocytes)

subtle dysfunction on HPA axis may be result of

comorbidity with depression

Autonomic dysfunction in anxiety disorders

• phobic disorders

• panic disorder

• PTSD

increases SNS activation

a2 adrenoceptor

GPCR in CNS - inhibits presynaptic neurotransmitter release

• if functional a2-adrenoceptor agonists

• a2 adrenoceptor antagonists raise bp

biomarkers of endocrine and autonomic dysfunction

some evidence of dysfunction in anxiety disorders

BUT

• inconsistent - differences between disorders, people