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Year 2 - Theme 3 > Anxiety disorders: Neurobiology, neurochemistry and treatment NS > Flashcards

Anxiety disorders: Neurobiology, neurochemistry and treatment NS Flashcards

1
Q

Nuclei of the amygdala

A

Basolateral region - Lateral, basal, accessory basal

Cortico-medial region - Central, medial and cortical

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2
Q

Where is the amygdala located

A
  • Medial temporal lobe
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3
Q

Where does the lateral nucleus of the amygdala receive input from

A
  • Sensory cortex

- Sensory thalamus

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4
Q

Output of lateral nucleus

A
  • Basolateral nucleus
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5
Q

Outputs of basolateral nucleus

A
  • Central nucleus
  • Ventral striatum + dorsomedial nucleus of thalamus
  • Basal nucleus
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6
Q

Inputs to basolateral nucleus

A
  • Lateral nucleus

- Hippocampal formation

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7
Q

Outputs of basal nucleus

A
  • Central nucleus

- Periaqueductal gray matter

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8
Q

Inputs to central nucleus

A
  • Basolateral nucleus

- Basal nucleus

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9
Q

Outputs of central nucleus

A
  • Hypothalamus
  • Midbrain
  • Pons
  • Medulla
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10
Q

Input to medial nucleus

A
  • main and accessory olfactory bulb
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11
Q

Output of medial nucleus

A
  • Medial basal forebrain and hypothalamus
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12
Q

Amygdala pathway via lateral hypothalamus

A

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

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13
Q

Amygdala pathway via VTA and LC

A

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

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14
Q

Amygdala pathway via paraventricular nucleus

A

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

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15
Q

What does the amygdala excite during a stress response

A
  • Sensory info channeled to amygdala

- Amygdala excites LC + hypothalamus

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16
Q

Acute stress response - HPA axis

A 
Hypothalamus releases CRH
Pituitary releases ACTH 
Adrenal cortex releases cortisol
	(stress hormone)
(CRH: corticotropin releasing hormone
ACTH: adrenocorticotropic hormone)
17
Q

Acute stress response - LC

A

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

18
Q

Characteristics of stress response

A

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
19
Q

How does cortisol cause negative feedback on stress response

A
  • Cortisol excites hippocampus

- Hippocampus has inhibitory effect on HPA

20
Q

Effect of chronic stress on hippocampus

A

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

21
Q

Link between anxiety disorders and hippocampus and amygdala

A
  • diminished activity of hippocampus
  • loss of feedback to the amygdala
  • inappropriate fear responding
    (evidence - hippocampal volume in PTSD patients reduced)
22
Q

Serotonergic vs Norepinephrine systems

A

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

23
Q

Balance of NE and 5-HT in panic attacks

A

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

24
Q

Features of OCD

A

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

25
Q

Incidence of OCD

A

1-2%

26
Q

Categories of compulsions

A

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

27
Q

OCD - genetics

A
  • Greater concordance with monozygotic than dizygotic twins

* Common underlying genotype for Tourette’s and OCD

28
Q

Environmental cause of OCD

A
  • Streptococcal infection

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

29
Q

What other condition is OCD associated with

A

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

30
Q

Link between indirect and direct pathways and OCD

A

• Imbalance between indirect and direct pathways through basal ganglia

31
Q

Role of direct and indirect pathways in OCD

A

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

32
Q

Best drugs to treat OCD

A

SSRIs best drugs for treating OCD, e.g. fluoxetine

but also clomipramine (TCA)

33
Q

OCD and caudate hyperactivity

A

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.

34
Q

Comparison of biological changes caused by CBT and SSRIs

A
  • Lead to a similar biological change
35
Q

OCD and OFC dysfunction

A 
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)

36
Q

Use of benzodiazepines in OCD

A
  • Good immediate effects, but patients can develop tolerance and there is potential for abuse, and anxiety
37
Q

SSRIs - OCD

A

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

38
Q

Combination of benzodiazepines and SSRIs - OCD

A

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

39
Q

Regions of the amygdala

A
  • Basolateral

- Cortico-medial

Year 2 - Theme 3 (9 decks)

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