Anxiety disorders: Neurobiology, neurochemistry and treatment NS

Question 1

Nuclei of the amygdala

Answer 1

Basolateral region - Lateral, basal, accessory basal

Cortico-medial region - Central, medial and cortical

Question 2

Where is the amygdala located

Answer 2

• Medial temporal lobe

Question 3

Where does the lateral nucleus of the amygdala receive input from

Answer 3

• Sensory cortex

- Sensory thalamus

Question 4

Output of lateral nucleus

Answer 4

• Basolateral nucleus

Question 5

Outputs of basolateral nucleus

Answer 5

• Central nucleus
• Ventral striatum + dorsomedial nucleus of thalamus
• Basal nucleus

Question 6

Inputs to basolateral nucleus

Answer 6

• Lateral nucleus

- Hippocampal formation

Question 7

Outputs of basal nucleus

Answer 7

• Central nucleus

- Periaqueductal gray matter

Question 8

Inputs to central nucleus

Answer 8

• Basolateral nucleus

- Basal nucleus

Question 9

Outputs of central nucleus

Answer 9

• Hypothalamus
• Midbrain
• Pons
• Medulla

Question 10

Input to medial nucleus

Answer 10

• main and accessory olfactory bulb

Question 11

Output of medial nucleus

Answer 11

• Medial basal forebrain and hypothalamus

Question 12

Amygdala pathway via lateral hypothalamus

Answer 12

Amygdala –> Lateral hypothalamus –> sympathetic activation –> tachycardia, galvanic skin response paleness, pupil dilation, blood pressure elevation

Question 13

Amygdala pathway via VTA and LC

Answer 13

Amygdala –> VTA, LC, dorsal lateral tegmental nucleus –> activation of dopamine, norepinephrine and acetylcholine –> Behavioural and EEG arousal increased vigilance

Question 14

Amygdala pathway via paraventricular nucleus

Answer 14

Amygdala –> ACTH release –> corticosteroid release(stress response)

Question 15

What does the amygdala excite during a stress response

Answer 15

• Sensory info channeled to amygdala

- Amygdala excites LC + hypothalamus

Question 16

Acute stress response - HPA axis

Answer 16

Hypothalamus releases CRH
Pituitary releases ACTH 
Adrenal cortex releases cortisol
	(stress hormone)
(CRH: corticotropin releasing hormone
ACTH: adrenocorticotropic hormone)

Question 17

Acute stress response - LC

Answer 17

Locus Coeruleus (LC)
releases norepinephrine
which triggers
“fight or flight” responses

Question 18

Characteristics of stress response

Answer 18

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

Question 19

How does cortisol cause negative feedback on stress response

Answer 19

• Cortisol excites hippocampus

- Hippocampus has inhibitory effect on HPA

Question 20

Effect of chronic stress on hippocampus

Answer 20

Chronic activation of glucocorticoid receptors in hippocampus
- increased Ca2+ entry into neurons
- too much Ca2+ - excitotoxic - cells die
Hippocampus can’t feedback to limit cortisol production

Question 21

Link between anxiety disorders and hippocampus and amygdala

Answer 21

• diminished activity of hippocampus
• loss of feedback to the amygdala
• inappropriate fear responding
  (evidence - hippocampal volume in PTSD patients reduced)

Question 22

Serotonergic vs Norepinephrine systems

Answer 22

Serotonergic systems and Norepinephrine systems project diffusely through the brain and are thought to have opposing functions.
NE release stimulates arousal and alertness
5-HT inhibits Norepinephrine (NE) release
Opposing functions in various brain areas
hippocampus
amygdala
hypothalamus

Question 23

Balance of NE and 5-HT in panic attacks

Answer 23

Shifted balance between the pathways to NE may be
manifested in Panic Attacks - fear responses to
inappropriate stimuli
SSRIs, by increasing 5-HT release, will push balance back

Question 24

Features of OCD

Answer 24

Frequently recurring, uncontrollable, anxiety-producing thoughts (obsessions) and impulses (compulsions). Responding to them, e.g. repeated, compulsive hand washing, dissipates associated anxiety.
OCD patients recognize their thoughts and behaviours are senseless

Question 25

Incidence of OCD

Answer 25

1-2%

Question 26

Categories of compulsions

Answer 26

counting, checking, cleaning, avoidance (exaggeration of natural human tendencies) e.g. trichotillomania, onychophagia

Question 27

OCD - genetics

Answer 27

* Greater concordance with monozygotic than dizygotic twins | * Common underlying genotype for Tourette’s and OCD

Question 28

Environmental cause of OCD

Answer 28

- Streptococcal infection | - experience also plays a role(eg stressful life events)

Question 29

What other condition is OCD associated with

Answer 29

• Associated with Tourette’s syndrome – hereditary chronic motor tic disorder (muscular and vocal tics) that has its locus in the basal ganglia

Question 30

Link between indirect and direct pathways and OCD

Answer 30

• Imbalance between indirect and direct pathways through basal ganglia

Question 31

Role of direct and indirect pathways in OCD

Answer 31

Direct pathway controlling previously learned behavioural sequences so they become automatic and can be rapidly executed Indirect pathway involved in suppressing these automatic behaviours allowing the person to switch to other more adaptive behaviours (behavioural flexibility). Overactivity of direct pathway may lead to these compulsive behaviours without being able to switch them off

Question 32

Best drugs to treat OCD

Answer 32

SSRIs best drugs for treating OCD, e.g. fluoxetine | but also clomipramine (TCA)

Question 33

OCD and caudate hyperactivity

Answer 33

The caudate sends GABAergic inhibitory projections to the GP, which sends inhibitory projections to the thalamus, which then projects to the OFC. It’s possible that OCD involves a disinhibition which leads to activity reverberating in this circuit.

Question 34

Comparison of biological changes caused by CBT and SSRIs

Answer 34

- Lead to a similar biological change

Question 35

OCD and OFC dysfunction

Answer 35

``` Underactivation of OFC in a reversal learning task in patients with OCD and their unaffected relatives, Chamberlain et al, Science, 2008. ``` New endophenotype for OCD. (vulnerability marker)

Question 36

Use of benzodiazepines in OCD

Answer 36

- Good immediate effects, but patients can develop tolerance and there is potential for abuse, and anxiety

Question 37

SSRIs - OCD

Answer 37

SSRIs are effective, but have a delayed onset. Initially can be anxiogenic

Question 38

Combination of benzodiazepines and SSRIs - OCD

Answer 38

Combining benzodiazepines and SSRIs initially and then tapering off the BDZs as the SSRIs take effect is an alternative treatment strategy

Question 39

Regions of the amygdala

Answer 39

- Basolateral | - Cortico-medial