anxiety

Question 1

what can anxiety be defined as?

Answer 1

a feeling of unease (worry, fear), which can range from mild to moderate
-psychological and physiological

Question 2

what is anxiety normally like and when does it become a problem?

Answer 2

the intensity normally is intermittent, and the source of anxiety is due to specific events/situations

it becomes a problem when the intensity is chronic and the source of anxiety is irrational
-when it impacts on activities of daily living, causing isolation and avoidance

Question 3

what can cause the symptoms of anxiety?

Answer 3

• past experiences/childhood experiences
• everyday life/habits
• diet - some food can trigger symptoms of anxiety, like caffeine or sugar
• drugs
• physical/mental health can trigger or exacerbate anxiety
• genetics

Question 4

drugs/alcohol and anxiety?

Answer 4

alcohol is a depressant and has a sedative effect - this is short-lived

then there is subsequent neurotransmitter imbalance (e.g. GABA, glutamate) which leads to anxiety symptoms

recreational drugs (cannabis, cocaine) have also been linked to anxiety symptoms

Question 5

what role does genetics play in anxiety?

Answer 5

anxiety disorders not based on a single gene

research has linked genetic factors to a number of anxiety disorders (e.g. panic disorder) - but the genetic risk is moderate

Question 6

symptoms of anxiety?

Answer 6

• avoidance behaviours
• social disturbances
• constant worry
• concentration/memory problems

Question 7

how are anxiety disorders classified?

Answer 7

DSM-V 2013 classification

anxiety disorders

• Generalised anxiety disorder (GAD)
• Specific phobias (e.g. agoraphobia)
• Panic disorder
• Social phobias (e.g. selective mutism)

obesessive and compulsive related disorders

• Obsessive compulsive disorder (OCD)
• PTSD

Question 8

what is GAD?

Answer 8

• ongoing state of excessive anxiety lacking clear reason or focus
• Excessive anxiety and worry occurring for at least six months, which is difficult to control and impairs activities of daily living.
• Associated with three or more (of six) symptoms.
• GAD sufferers symptoms likely to be different from another persons experience with GAD

Question 9

Specific phobias?

Answer 9

extreme fears or anxieties provoked by exposure to a particular situation or object – often leads to avoidance behaviours
eg. Podophobia = fear of feet

Question 10

Panic disorder?

Answer 10

recurring panic attacks, without a cause or trigger

Panic attacks are sudden feelings of overwhelming fear with marked somatic symptoms (e.g. sweating, chest pains).

Panic attacks can occur spontaneously or be a feature of a number of anxiety disorders .

Question 11

Social phobias?

Answer 11

significant anxiety provoked by exposure to certain types of social (e.g. social gatherings) or performance (e.g. public speaking) situations.

Question 12

Selective mutism?

Answer 12

severe anxiety disorder where a person is unable to speak in certain social situations, such as with classmates at school or to relatives they do not see very often

Question 13

OCD?

Answer 13

compulsive, ritualistic behaviour driven by irrational anxiety.

obesessions - recurrent, intrusive thoughts, images, ideas or impulses.

and compulsions - Repetitive behaviours, performed to reduce anxiety associated with the obsessions

Question 14

PTSD?

Answer 14

flashbacks and nightmares

distress triggered by the recall of past traumatic experiences – can lead to flashbacks and nightmares

Question 15

Pathophysiology of anxiety disorders

Answer 15

inappropriate stress response either when a stressor is not present or not immediately threatening

• The stress response is regulated by the hypothalamus-pituitary-adrenal (HPA) axis.
• HPA axis leads to the release of cortisol (a glucocorticoid)
• Cortisol contributes to the body’s physiological response to stress

Question 16

role of amygdala and hippocampus in cortisol release?

Answer 16

amygdala stimulates HPA axis to release it, hippocampus inhibits HPA axis

so anxiety disorders come from hyperactivity of amygdala or hypoactivity of the hippocampus

Question 17

continuous exposure to cortisol affects the hippocampus how?

Answer 17

neuronal degeneration
-sets off a vicious cycle in which the stress response becomes more pronounced, greater cortisol release and more hippocampal damage.

-decrease in hippocampal volume in some people who suffer from PTSD

Question 18

drugs that treat anxiety are called?

Answer 18

Anxiolytic drugs

Question 19

types of anxiolytics?

Answer 19

GABAA receptor modulators (barbiturates and benzodiazepines)
5-HT1A receptor agonists
beta adrenoceptor antagonists

Question 20

GABA and glutamate levels in anxiety

Answer 20

imbalance between the major inhibitory neurotransmitter GABA and the major excitatory neurotransmitter glutamate in patients suffering from anxiety disorders - GABA neurotransmitter levels are often low.

Question 21

barbiturates

Answer 21

barbiturates no longer recommended for anxiety due to the severe depressant effect on the CNS

-Barbiturates increase the activity of GABAA receptors – binding increases channel
opening beyond that seen with GABA alone
-increase GABA efficacy
-positive allosteric modulators (PAMs)

at higher doses, they also:

• block nAChR, 5-HT3 and AMPA/kainate receptors
• block Ca2+-dependent neurotransmitter release

Question 22

Benzodiazepines

Answer 22

most widely used class of anxiolytics

• they bind to a distinct regulatory site on GABAa receptors (alpha gamma interface)
• stabilise the GABAa receptor binding site for GABA in the open configuration - increases GABA affinity for its binding site, produces general enhancement of its neuroinhibitory actions

Question 23

how do you choose which benzodiazepine o give to a patient?

Answer 23

choice made based on duration of action (e.g. short-acting preferred as hypnotics to avoid sedation throughout day)

Question 24

what are barbiturates and benzodiazepines associated with?

Answer 24

tolerance and withdrawal symptoms

tolerance is trafficking of additional glutamate receptors to the cell membrane - restores initial imbalance seen in the ”symptomatic” stage. Patients therefore need to take a higher dose of BZDs to address this new imbalance between inhibitory and excitatory neurotransmission

If a patient suddenly withdraws from taking these high doses of BZDs, there is a sudden decrease in inhibitory GABA neurotransmission. Coupled with increased excitatory glutamate neurotransmission, this can lead to the development of seizures

Question 25

5-HT1A receptor agonists

Answer 25

eg. Buspirone
treat anxiety – less tolerance and withdrawal symptoms compared to the benzodiazepines

activation of pre-synaptic 5-HT1A autoreceptors – inhibits 5-HT release BUT after a while it downregulates presynaptic receptors

reduces activity of noradrenergic neurons and decreases arousal (but does not induce sleep)

Question 26

SSRIs

Answer 26

inhibit serotonin re-uptake via SERT - increase in 5-HT availability

If SSRIs taken over a period a few weeks, they induce desensitisation of autoinhibitory 5-HT1A receptors - leads to downregulation of 5-HT1A receptors on the pre-synaptic plasma membrane

-However SSRIs can also lead to the downregulation of 5-HT receptors on the post-synaptic plasma membrane

Question 27

𝛽-Adrenoceptor antagonists

Answer 27

used to treat some symptoms of anxiety, eg. propranolol

reduce some peripheral manifestations of anxiety - tremor, sweating, tachycardia and diarrhoea

Question 28

adrenoceptor subtypes

Answer 28

α1 couples to Gq proteins to activate phospholipase C

α2 couples to Gi/o and inhibits adenylate cyclase

β1 and β2 couple to Gs and activate adenylate cyclase

beta 1 and beta have effects that include increasing renin release from JG cells, increasing heart rate, SM relaxation, glucose metabolism and increasing hunger