Anxiety disorders: neurology, neurochemistry and treatment Flashcards
Fearful stimuli elicit stress responses
Sensory information channeled to amygdala
Amygdala excites locus coeruleus and hypothalamus
Acute stress response
Hypothalamus releases CRH
Pituitary releases ACTH
Adrenal cortex releases cortisol
Locus coeruleus releases norepinephrine which triggers fight or flight responses
Characteristics of the stress response
Avoidance behaviour
Increased vigilance and arousal
Activation of the sympathetic division of the ANS
Release of cortisol from the adrenal glands
In situations of chronic stress
Chronic activation of glucocorticoid receptors in hippocampus
Increased Ca2+ entry into neurons
Too much Ca2+ makes it excitotoxic so cells die
Hippocampus can’t feeback to limit cortisol production
Some anxiety disorders may result from
Diminished activity of hippocampus
Loss of feedback to the amygdala
Inappropriate fear responding
Response of amygdala and hippocampus to highly processed information from other brain areas
Noradrenergic system- arousal and attention
Serotonergic system- mood and emtion
Post traumatic stress disorder
Persistent psychological stress following exposure to extreme stress
Panic disorder
Rapid onset attack of extreme fear and sever stress
Generalised anxiety disorder
Stress and anxiety in the absence of obvious precipitating stimuli
Phobias
Similar to GAD but triggered by particular objects of siduations
Obsessive compulsive disorder
Frequently recurring, uncontrollable, anxiety producing thoughts and impulses and responding to them
Treatment of panic disorder
Benzodiazepines, partial agonists of GABA receptor, anxiolytic
Serotonin, SSRIs
CBT
Benzodiazepines work well in
Generalised anxiety disorder
Panic disorder
Benzodiazepines not so effective in
OCD
PTSD
SSRIs work in
OCD
PTSD
PD
GAD
Buspirone
5-HT receptor partial agonist
Works for GAD
Drugs increasing GABA activity
Reduce anxiety
Partial agonist: alcohol
Indirect agonists: barbiturates, benzodiazepines
Drugs decreasing GABA activity
Increase anxiety
Benzodiazepine antagonist: flumazenil
Serotonergic system and anxiety
SSRIs
- prolong action of 5-HT in the synapse
Buspirone
- 5HT1A partial agonist
Somatodendritic receptor
- autoreceptors
Anxiety and depression
Often comorbid
Both treatable with SSRIs
Both weeks before therapeutic actions are visible
Neuroplasticity downstream of antidepressant actions
Intracellular cascades downstream of 5-HT receptor can lead to changes in plasticity and morphology
Obsessive compulsive disorder genetics
Greater concordance with monozygotic than dizygotic twins
Common underlying genotype for tourette’s and OCD
Can be environmental (strep infection)
OCD and basal ganglia
Associated with tourette’s syndrome- hereditary chronic motor tic disorder that has its locus in the basal ganglia
Imbalance between indirect and direct pathways through basal ganglia
OCD and caudate hyperactivity
Caudate sends GABAergic inhibitory projections to GP, sends inhibitory projections to thalamus, then projected to OFC
Possible that OCD involves disinhibition which leads to activity reverberating in this circuit
CBT and SSIRs lead to similar biological change
OCD and OFC dysfunction
Underactivation of OFC in a reversal learning task in patients with OCD and their affected relatives
New endophenotype for OCD
Treatment strategies
Benzodiazepines
- good immediate effects
- can develop tolerance and potential for abuse
- anxiety during withdrawal
SSRIs
- effective
- have delayed onset
- can be anxiogenic
Combining
