Anxiety

Question 1

Epidemiology and diagnostic criteria

Answer 1

Most common mood disorder in US
Must exhibit three of the following most days over 6 months:
-irritability
-feeling wound up, restless
-disrupted sleep
-trouble concentrating
- easily fatigued
-significant muscle tension

Question 2

Imaging studies

Answer 2

• Etkin and Wagner 2007 - patients with social anxiety or phobias have amygdala hyperactivation at rest, similar to that of healthy subjects during fear conditioning
• Anxiety and phobic patients have increased activity in amygdala, aCC during conditioning or looking at aversive stimuli.
• Same patients have decreased activity in ventrolateral PFC
• Indovina et al 2011 - used context-predicted US and cue-predicted US in humans. High trait anxiety correlated with increased amygdala activity in cue-predicted, and reduced vPFC recruitment in context-predicted. But these two did not correlate with each other, so trait anxiety comes from one or the other mechanism.
• Insula overactivation - representative of interoceptive information and risk coding?
• Critchley et al 2004 - Heartbeat awareness correlated with insula activity and volume, insula activity correlated with anxiety, heartbeat awareness correlated with anxiety
• BNST active during sustained ‘anxious’ responses to unpredictable threats
• Duvarci et al 2009 - Sham lesioned rats were on a continuum of poor to good discriminators (of CS vs unrelated cue). Poor discriminators did more contextual freezing and were more anxious on elevated plus maze. BNST lesioned rats all behaved like sham lesioned rats at the good discriminator end of the spectrum.

Question 3

Cold cognition effects

Answer 3

No effect! i.e. perfect performance on Tower of London task

Question 4

Hot cognitive effects - increased detection of and attendance to threat-related information

Answer 4

• Bishop 2008 - High trait anxiety makes people more likely to detect fear in ambiguous faces. They have normal results in fear conditioning though, perhaps because they overgeneralise the CS.
• anxious patients much more likely to detect threat-related stimuli than neutral stimuli, compared to controls who are more or less equal
• in GAD, patients can increase the range of stimuli they deem indicative of threat until almost anything is threatening
• Letter detection task with emotional distractors (letters printed on fear face) —> decreased dorsolateral PFC activity in anxious patients, suggestive of decreased top-down control

Question 5

Hot cognitive effects - deficient safety learning

Answer 5

Grillon and Morgan 1999 - Patients with PTSD have the same startle response to a non-conditioned stimulus as to a neutral stimulus!
Lihtik et al 2014 - Rats that are able to discriminate between CS+ and CS- have increased entrainment of the BLA of amygdala to the theta frequency from mPFC.

Question 6

Hot cognitive effects - negative interpretation of uncertainty

Answer 6

In ambiguous face presentation, anxious patients are more likely to identify it as a negative emotion (sadness, fear, surprise). Amygdala overactive only in detection of fear or surprise.
when presented aurally with homophones (e.g. die/dye), anxious patients more likely to identify the word as the more negative option

Question 7

Hot cognitive effects - higher estimation of threat probability

Answer 7

Circles of gradually increasing size are cues. The biggest one comes with a shock. Patients with GAD have increased startle responses and are more likely to predict the shock from the cue given

Question 8

Hot cognitive effects - Increased threat avoidance

Answer 8

inactivation of OFC or vlPFC introduced a bias away from punishment in marmosets, which was ameliorated by anxiolytic treatment
The OFC effects were delayed and dependent upon amygdala-anterior hippocampus circuit
anxious patients are risk averse, not loss averse (determined by a win/lose vs nothing choice, then a win vs win-more/nothing choice - choosing ‘nothing’ in the former could be due to loss aversion or risk aversion, the latter could only be due to risk aversion)

Question 9

Treatments

Answer 9

CBT increases PFC activation and control of subcortical structures
Benzodiazepines bind to GABA<a>, anziolytic when infused into amygdala, effect abolished when flumazenil (BZA antagonist) also infused in, highly addictive, contraindicated in alcohol use
SSRIs are acutely anxiogenic (increased recognition of fearful faces) and chronically anxiolytic (over 8 weeks)</a>

Question 10

Monoaminergic hypothesis…?

Answer 10

ATD has no effect on anxiety of healthy or anxious patients.
DOES increase panic in panic disorder patients ONLY when challenged with anxiogenic stimuli (CO2 or flumazenil)
DOES NOT increase panic in healthy patients even when challenged
DOES NOT increase threat prediction in GAD patients remitted after SSRI use, whether challenged or not (SSRIs work!)
this suggests that 5-HT may be protective in the presence of panicogens, but tonically elevated 5-HT is not the main mode of action of SSRIs
SAD patients have reduced 5-HT1A binding sites across brain, esp raphe nucleus
5-HT1A partial agonist (buspirone) is anxiolytic
5-HT1A KO or antagonism is highly anxiogenic