Lecture 49: Neurobiology of Anxiety

Question 1

What is the normal anxiety response?

Answer 1

Promotes optimal functioning (anxiety when you are trying to make it to class on time)

Question 2

What is abnormal anxiety response?

Answer 2

Interferes with functioning

Question 3

How do you want to think of anxiety?

Answer 3

Continuum of anxiety
Worry  Panic
Worry is least anxious
Panic is most anxious

Question 4

What is the Yerkes-Dodson Law?

Answer 4

Medium amount of arousal leads to highest performance…don’t want to be too worried or too relaxed

Question 5

What axis regulates anxiety?

Answer 5

The HPA (hypothalamo-pituitary-adreno) Axis

Question 6

What is the General Adaptation Syndrome?

Answer 6

Used for coping with stress
Sympathetic response (caused by release of Epi and NE from adrenal medulla)
Long term adjustments = mobilization of remaining energy reserves/conservation of glucose
Can lead to exhaustion phase where vital systems collapse
-exhaustion of lipid reserves
-inability to produce glucocorticoids
-failure of electrolyte balance

Question 7

What are the different biological mechanisms of anxiety?

Answer 7

1. Neurochemical
2. Genetic
3. Neuroanatomical
4. neurofunctional

Question 8

What regulates the neurochemistry of anxiety?

Answer 8

1. Monoaminergic neurons with wide range
   
   • Raphe nuclei = serotonin
   • Locus coeruleus = NE
   • some DA neurons
   • GABA

Question 9

What is the role of GABA in anxiety?

Answer 9

Two distinct types of GABA receptors?
	i. GABA-A is LINKED with anxiety
	-allows Cl- to enter cell
	-fast acting (ionotropic)
Pentamer of 5 unites

Question 10

What is the significance of GABA-A?

Answer 10

One type of GABA receptor
-linked with anxiety
-binds to barbiturate, steroid, ethanol and GABA lol
Can Inhibit anxiety when activated or deactivated?

Question 11

What is the role of Serotonin in anxiety?

Answer 11

Synthesized In discrete brainstem nuclei in median/dorsal raphe
Drugs that block re-uptake of 5-HTs have positive results
-antidepressants = SSRIs
-also works on anxiety
More serotonin the better…

Question 12

What is the role of Norepinephrine in anxiety?

Answer 12

Excessive sympathetic activation may produce dysfunctional arousal
Alpha 2 NE receptor is associated with anxiety/depression

Question 13

What is the role of Dopamine in anxiety?

Answer 13

-seen in substantia nigra, ventral tegmental area
-involved in reward pathway (VTA, nucleus accumbens, cingulate)
Not much is known in relation to SAD, PTSD and OCD

Question 14

What are the key points about the genetics of anxiety?

Answer 14

People who are more likely to be behavioral inhibition will be more anxious
Neuroticism
-predisposes to GAD
-associated with allelic variations in promoters region of serotonin transporter gene
- moderately heritable

Question 15

What is neuroticism associated with?

Answer 15

Allelic variations in promoter in serotonin transporter gene
SMALLER amygdala and cingulate
Abnormal hippocampal and fronto-limbic activity

Question 16

What is classical conditioning?

Answer 16

Pavlov’s dog…salivate when hearing bell

Question 17

What is operant conditioning?

Answer 17

Reward, punishment and EXTINCTION

Question 18

What is reinforcement?

Answer 18

Anything that increases likelihood of a behavior
Positive reinforcers (doing something positive)
Negative reinforces (removing aversive stimulus after response)

Question 19

What is punishment?

Answer 19

Anything that decreases likelihood of a behavior
Positive punishment = presenting aversive stimulus after response
Negative punishment = removing positive stimulus after response (no TV)

Question 20

What is the behavioral model for anxiety disorders?

Answer 20

Anxiety begins with classical conditioning

It is maintained through operant condition (negative reinforcement)

Question 21

What is fear extinction?

Answer 21

Learning not to fear
-presenting conditioning stimulus WITHOUT unconditioned stimulus will lead to extinction (gradual process)
-important adaptation that can allow suppression of previous fear (kind of like OCD treatment)
It is NEW learning
It is NOT forgetting
-context dependent: fear response can still occur in contexts that are different from where extinction occurred

Question 22

What is exposure treatment?

Answer 22

Fear memory is never “erased”
So competition between safety learning and fear learning is resolved by context
-contexts may include time, drug state, therapists presence, stimulus
It is important to conduct extinction training in MULTIPLE contexts

Question 23

What happens to conditioned response as a result of extinction learning?

Answer 23

CR returns after rest period (after extinction training)
If extinction occurs in different environment than acquisition, putting animal back in orginal environment evokes CR again
Reinstatement of fear from US can reinstate CR

Question 24

What are the key areas of brain involved in stress response?

Answer 24

Locus coeruleus (sympathetic activation
Limbic system (Papez)
Hippocampus, fornix, mammillary bodies, thalamus, cingulate, amygdala/hypothalamus
Integrated system
	-PFC
	-amygdala

Question 25

What is the significance of Papez circuit?

Answer 25

Emotional representaitons from thalamus to 1. Cortex (stream of thinking) 2. Hypothalamus (stream of feeling) Output from cingulate cortex allows for top-down control of emotional responses -eg you’re at a funeral so you shouldn’t laugh

Question 26

What is connection between PFC and amygdala?

Answer 26

PFC can augment or inhibit amygdala response to stimulus

Question 27

What do fearful expressions activate?

Answer 27

Amygdala…doesn’t require conscious recognition…subconscious stimuli processing

Question 28

What is amygdala associated with?

Answer 28

Associated with fear in response to cue -associated with fear in response to context Amygdala associated with all types of fear

Question 29

What is the hippocampus associated with?

Answer 29

Associated with fear in response to context