Anxiety disorders: neurology, neurochemistry and treatment

Question 1

Fearful stimuli elicit stress responses

Answer 1

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

Question 2

Characteristics of the stress response

Answer 2

Avoidance behaviour

Increased vigilance and arousal

Activation of the sympathetic division of the ANS

Release of cortisol from the adrenal glands

Question 3

In situations of chronic stress

Answer 3

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

Question 4

Some anxiety disorders may result from

Answer 4

Diminished activity of hippocampus

Loss of feedback to the amygdala

Inappropriate fear responding

Question 5

Response of amygdala and hippocampus to highly processed information from other brain areas

Answer 5

Noradrenergic system- arousal and attention

Serotonergic system- mood and emtion

Question 6

Post traumatic stress disorder

Answer 6

Persistent psychological stress following exposure to extreme stress

Question 7

Panic disorder

Answer 7

Rapid onset attack of extreme fear and sever stress

Question 8

Generalised anxiety disorder

Answer 8

Stress and anxiety in the absence of obvious precipitating stimuli

Question 9

Phobias

Answer 9

Similar to GAD but triggered by particular objects of siduations

Question 10

Obsessive compulsive disorder

Answer 10

Frequently recurring, uncontrollable, anxiety producing thoughts and impulses and responding to them

Question 11

Treatment of panic disorder

Answer 11

Benzodiazepines, partial agonists of GABA receptor, anxiolytic

Serotonin, SSRIs

CBT

Question 12

Benzodiazepines work well in

Answer 12

Generalised anxiety disorder

Panic disorder

Question 13

Benzodiazepines not so effective in

Answer 13

OCD

PTSD

Question 14

SSRIs work in

Answer 14

OCD

PTSD

PD

GAD

Question 15

Buspirone

Answer 15

5-HT receptor partial agonist

Works for GAD

Question 16

Drugs increasing GABA activity

Answer 16

Reduce anxiety

Partial agonist: alcohol

Indirect agonists: barbiturates, benzodiazepines

Question 17

Drugs decreasing GABA activity

Answer 17

Increase anxiety

Benzodiazepine antagonist: flumazenil

Question 18

Serotonergic system and anxiety

Answer 18

SSRIs
- prolong action of 5-HT in the synapse

Buspirone
- 5HT1A partial agonist

Somatodendritic receptor
- autoreceptors

Question 19

Anxiety and depression

Answer 19

Often comorbid

Both treatable with SSRIs
Both weeks before therapeutic actions are visible

Question 20

Neuroplasticity downstream of antidepressant actions

Answer 20

Intracellular cascades downstream of 5-HT receptor can lead to changes in plasticity and morphology

Question 21

Obsessive compulsive disorder genetics

Answer 21

Greater concordance with monozygotic than dizygotic twins

Common underlying genotype for tourette’s and OCD

Can be environmental (strep infection)

Question 22

OCD and basal ganglia

Answer 22

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

Question 23

OCD and caudate hyperactivity

Answer 23

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

Question 24

OCD and OFC dysfunction

Answer 24

Underactivation of OFC in a reversal learning task in patients with OCD and their affected relatives

New endophenotype for OCD

Question 25

Treatment strategies

Answer 25

Benzodiazepines

• good immediate effects
• can develop tolerance and potential for abuse
• anxiety during withdrawal

SSRIs

• effective
• have delayed onset
• can be anxiogenic

Combining