Chapter 8-Essential Psychopharm

Question 1

Overlap and Unique symptoms of MDD and Anxiety disorders

Answer 1

1. Overlap: concentration, sleep, fatigue, psychomotor, arousal
2. Unique MDD:
   a. depressed mood, decreased interest/pleasure, feelings of guilt/worthlessness, suicidality, appetite/weight changes
3. Unique anxiety symptoms:
   a. anxiety, worry, irritability, muscle tension, compulsions, phobic avoidance, panic attacks

Question 2

GAD and Panic Disorder

Answer 2

1. GAD Core symptoms: generalized anxiety/fear and generalized worry
2. PD core symptoms: anticipatory anxiety/fear and worry about panic attacks
   a. PD associated symptoms: unexpected panic attacks and phobic avoidance/behavioral changes

Question 3

Social Anxiety Disorder and PTSD

Answer 3

1. SAD- core symptoms are anxiety or fear over social performance AND worry about social exposure.
   a. Associated symptoms are panic attacks that are predictable and expected in certain social situations as well as phobic avoidance of those situations.
2. PTSD- Core symptoms are anxiety while the traumatic event is being reexperienced AND worry about having the other symptoms of PTSD (arousal, startle, insomnia, nightmares, avoidance)
   a. Considered a disorder of hyperarousal (stress related disorder).

Question 4

Anxiety Phenotype

Answer 4

a. Fear
1. panic
2. phobia
3. Amygdala-centered circuit

b. Worry
1. anxious misery
2. apprehensive expectation
3. obsessions
4. cortico-striatal-thalamo-cortical circuit (CSTC)

Question 5

Amygdala and the neurobiology of fear

Answer 5

1. Integrates sensory and cognitive information to determine if there will be a fear response
2. Shares receiprocal connections with prefrontal cortex to regulate emotions
   a. orbitofrontal cortex
   b. anterior cinculate cortex
3. Fear motor response
   a. fight, flight, freeze
   b. regulated in part by the periaqueductal gray area of the brainstem
4. Endocrine reactions
   a. HPAaxis- impacts cortisol levels
   b. chronic HPA axis activation can lead to CAD, type 2 DM, stroke , and hippocampal atrophy
5. Respiration reaction
   a. connections between amygdala and the parabrachial nucleus in the brainstem
6. ANS is attuned to fear
   a. can trigger increased pulse rate, HR, blood pressure
   b. meditated by connections between amygdala and the locus coeruleus
7. Neurobiological regulators of the amygdala
   a. GABA, 5HT, NE, Voltage gated calcium channels

Question 6

Cortico-striato-thalamo-cortical (CSTC) loops and the neurobiology of worry

Answer 6

1. Prefrontal cortex
2. Worry includes anxiois misery, apprehensive expectatiosn, catastrophic thinking, obsessions.
3. Neurotransmitters and regulators: 5HT, GABA, dopamine, NE, glutamate, voltage-gated ion channels

Question 7

Benozs for Anxiety

Answer 7

1. Excessive amygdala activity is thoeretically reduced by bonzodiazepines.
   a. the enhance inhibition of GABA by positive allosteric modulation of postsynaptic GABAa receptors.
   b. the anxiolytic actions of benozos are hypothetically at GABAa receptors localized within the amygdala where bonzos hypothetically blunt fear-assoicated outputs
2. Benozso also theoretically modulate excessive output from worry loops by enhancing actions of inhibitory interneurons in CSTC circuits and reducing worry.

Question 8

Alpha-2-delta ligands as anxiolytics

Answer 8

1. Alpha-2-delta ligands (gabapentin and pregabalin)
   a. bind to the alpha-2delta subunit of presynaptic N and P/Q VSCCs,
   b. block the release of excitatory neurotransmitters such s glutamate
   c. hypothetically bind to open, overaly active VSCCs in the amygdala to reduce fear and in the CSTC circuits to reduce worry
   d. have anxiolytic actions in social anxiety disorder and panic disorder

Question 9

Serotonin and anxiety

Answer 9

1. 5HT is a key neurotransmitter that innerates the amygdala and elements of the CSTC circuits (PFC, striatum, and thalamus)
2. 5HT can regulate fear and worry.
3. 5HT1a partial agonist (buspar) is recognized to treat GAD but not other anxiety disorders
   a. buspart has 5HT1a partial agonist actions at presynaptic and postsynaptic 5HT1a receptors

Question 10

Norepinephrine and anxiety

Answer 10

1. excessive NE output from locus coeruleus can result in autonomic overdrive and trigger symptoms of anxiety and fear (nightmares, flashbacks, panic attacks, hyperarousal).
2. excessive NE can reduce efficiency of information processing in the PFC and CSTC circuits
3. nightmares symptoms can be reduced with a1 adrenergic blockers (prazocin)
4. symptoms of fear and worry can be reduced by NET inhibitors.

Question 11

Fear conditioning versus Fear extinction

Answer 11

1. Fear conditioning
   a. amygdala can remember stimuli associated with a stressful/fearful experience by increasing efficiency of glutamate neurotransmission
   b. so when future exposure occurs, a fear response is triggered.
   c. if not countered by input from VMPFC to suppress fear, then conditioning proceeds.
   d. Can not be reversed but can be inhibited through new learning.
2. Fear extinction
   a. The new learning is called fear extinction.
   b. progressive reduction of the response to a feared stimulus without adverse consequences
   c. VMPFC and hippocampus learn a new context and send input to the amygdala to suppress the fear response.
3. Beta blockers and opiates prevent fear conditioning and reconsolidation of fear