anxiety Flashcards
What is anxiety?
Anxiety can be defined as a feeling of unease (e.g. worry or fear), which can range from mild to severe.
Anxiety is an innate response
- Fear is an adaptive response to a threatening stimuli
- Fear response comprises several components (e.g. defensive behaviours, autonomic reflexes, increased alertness)
- Many fears are innate and species specific
Anxiety is a learned adaptive response
- Fears can also be learned through life experiences (e.g. not touching a hot stove)
- However, fear is not an appropriate response in all circumstances
- Fear response can occur in an anticipatory manner, sometimes independently of stimuli
Negative aspects of anxiety
Social disturbances
Avoidance behaviours
incessant worry
Concentration/memory problems
Some physiological symptoms
- Tachycardia
- Shortness of breath
- Excessive sweating
- Trembling or shaking
- Headache and dizziness
- Pins and needles
- Gastrointestinal disturbances
- Nausea
- Fatigue
- Insomnia
Some Causes symptoms of anxiety?
Past experiences
Everyday life and habits
Diet
Physical and mental health
How alcohol and drugs can trigger anxiety
- Alcohol is a central nervous system (CNS) depressant – increases GABAergic neurotransmission and can block glutamatergic neurotransmission
- Balance between GABA and glutamate crucial for optimal brain function – alcohol disrupts this balance
Genetics as a possible cause
- Research has linked genetic factors to several anxiety disorders (e.g. panic disorder)
- However, the only clear result that can be derived from genetic studies is that anxiety disorders are not based on a single gene but likely have a complex genetic basis, which can be affected by environmental factors
Balance of GABA and glutamate disrupted by Drugs and alcohol
Our brain adapts to counteract this imbalance – leads to low levels of GABA and high levels of glutamate can trigger anxiety symptoms • Recreational drugs of abuse (e.g. psychostimulants) can also trigger anxiety symptoms via mechanisms unique to a drug or class of drugs
Stress mechanism
The stress response is the co-ordinated reaction to threatening stimuli:
• The stress response is regulated by the hypothalamus-pituitary-adrenal (HPA) axis
• The HPA axis regulates the release of cortisol (a glucocorticoid), which contributes to the body’s physiological response to stress
How anxiety disrupts the stress mechanism
It is evident that the activation of CRH-releasing hormones of the hypothalamus play a key role in regulating the stress response:
• Overexpressing CRH in rodent models lead to increased anxiety-like behaviours
• Knocking out CRH receptors in rodent models leads to less anxiety-like behaviours
What does CRH stand for?
Corticotropin-releasing hormone
Amygdala’s role in emotion and fear
• Stimulates HPA axis (green) to promote cortisol release
• Amygdala hyperactivity linked to anxiety disorders
too much = anxiety
Hippocampus’ role in emotion and fear
- Hippocampus – role in learning and memory
- Suppresses HPA axis (red) to prevent excessive cortisol release
- Hippocampus underactivity linked to anxiety disorders
Anxiety disorders
- Generalised anxiety disorder (GAD)
- Specific phobias
- Social phobias
- Panic disorder
Obsessive compulsive disorders
Obsessive-compulsive disorder (OCD) Other disorders include: Body dysmorphic disorder Hoarding disorder Trichotillomania (hair-pulling disorder)
Generalised Anxiety disorder (GAD)
Generalised anxiety disorder (GAD) is characterised by an 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
• Not attributable to a substance or medical condition or better explained by another type of anxiety disorder
• GAD sufferers’ symptoms likely to be different from another person’s experience with GAD
Specific phobias
Specific phobias are extreme fears or anxieties provoked by exposure to a particular situation or object – often leads to avoidance behaviours.
Social phobias
- Social phobia may relate to one or more social situations in which the individual is exposed to possible scrutiny by others
- Includes social interactions, being observed and performing in front of others
- Social situations almost always provokes immediate fear or anxiety – this is out of proportion to the actual danger posed by the object or situation
- Phobia is persistent and typically persists for at least six months, impairing activities of daily living
- Not attributable to a substance or medical condition or better explained by another type of anxiety disorder
OCD
Obsessions
Recurrent, intrusive thoughts, images, ideas or impulses
Compulsions
Repetitive behaviours or mental acts that are performed to reduce anxiety associated with the obsessions
Post-traumatic stress disorder (PTSD)
Post-traumatic stress disorder (PTSD) is characterised by distress triggered by the recall of past traumatic experiences.
• Triggered by exposure to certain situations – actual or threatened death, serious injury or sexual violence
Anxiety disorder treatment
Psychological - Cognitive behavioural therapy (CBT)
Pharmacological - Anxiolytics
Anxiolytic drugs
Anxiolytics are a class of drugs used to treat anxiety disorders.
Benzodiazepines
Benzodiazepines are a class of GABAA receptor positive allosteric modulators.
• Benzodiazepines bind to a distinct regulatory site on GABAA receptors
• Benzodiazepines stabilise the GABAA receptor binding site for GABA in the open configuration
• Benzodiazepines therefore increases GABA affinity for its binding site and produces a general enhancement of its neuroinhibitory actions
• Benzodiazepines are therefore classed as positive allosteric modulators
Midazolam
Ultrashort (< 6 hours)
Anaesthetic
Lorazepam
Short (12-18 hours)
Anxiolytic, hypnotic, anti-convulsant
Alprazolam
Medium (24 hours)
Anxiolytic
Diazepam
Long (24-48 hours)
Anxiolytic, anti-convulsant
Benzodiazepines
Benzodiazepines act as positive allosteric modulators at the GABAA receptor to stabilise the GABAA receptor binding site for GABA in the open configuration.
Tolerance
This serves to restore the initial imbalance seen in the symptomatic stage. An individual therefore needs to take a higher dose of benzodiazepines to address this new imbalance between inhibitory and excitatory neurotransmission.
Withdrawal
If the individual suddenly withdraws from taking these high doses of benzodiazepines, there is a sudden decrease in inhibitory GABA neurotransmission. Coupled with increased excitatory glutamate neurotransmission, this can lead to heightened anxiety and various other side-effects
5-HT1A receptor
Serotonin (5-HT) is a neurotransmitter in the peripheral nervous system (PNS) and in the central nervous system (CNS).
The function of 5-HT receptor
Important roles in sleep and wakefulness, in addition to mood and emotional behaviours
5-HT1A receptor function
- Buspirone’s side-effects are less troublesome than benzodiazepines – include dizziness, nausea and headache
- Buspirone activates 5-HT1A auto-receptors – this inhibits 5-HT release
- Buspirone also inhibits the activation of noradrenergic neurons – decreases arousal reactions
Noradrenaline function
- Noradrenaline is the major neurotransmitter of the sympathetic nervous system (e.g. cardiovascular tone)
- Noradrenaline also has roles in attention, arousal and sleep and wakefulness
Drug noradrenaline function
• A drug target for peripheral manifestations of anxiety (e.g. 𝝱-noradrenergic receptor antagonists)
𝛽-noradrenergic receptors antagonists
𝛽-noradrenergic receptor antagonists (e.g. propranolol) are a class of drugs that can be used to treat some forms of anxiety. • Propranolol is non-selective between 𝛽1 and 𝛽2 noradrenergic receptors • 𝛽-noradrenergic antagonists reduce some of the peripheral manifestations of anxiety
Include tachycardia, sweating, gastrointestinal problems and tremor