week 12 Flashcards
Define Anxiety
An adaptive state of increased apprehension that helps an animal avoid potential danger, and it is associated with muscle tension and vigilance
An cautious or avoidant behaviours
Includes panic
Define Fear
Emotional response to real or perceived imminent threat
What does fear include?
surges of autonomic arousal necessary for fight or flight
Thoughts of immediate danger, and escape behaviours
What is anxiety related to?
Fear
It is not the same
What is anxiety a umbrella term for?
A variety of disorders
within DSM-5
What are the manifestations of anxiety disorder?
Both psychological and physical
What are examples of potential stressors?
- Failures
- Personal losses
- Frightening events
- Time precursors
- Insults
When the potential stressors are perceived as a threat, what is it subdivided into?
- Bodily effects
2. Upsetting thoughts
What are examples of bodily effects?
- Autonomic emergency response
- Shallow breathing
- Pounding heart
- Tense muscles
- Digestive problems
- Sleep disturbances
- Fatigue
- Psychosomatic illness
What are examples of upsetting thoughts?
- Anger
- Fears
- Preoccupations
- Self-doubts
- Negative self-talk
- Repeated ‘‘danger’’ thoughts
- Worry about body reactions and health
What does bodily effects and upsetting thoughts lead to?
Ineffective behaviour
What is an example of ineffective behaviour?
- Escape
- Avoidance
- Indecision
- Aggression
- Inflexible responses
- Poor judgement
- Inefficiency
- Drug use
What is ineffective behaviour’?
Behaviour you engage that has no actual purpose or produce no result
What is fear processing?
- Thalamus projects to amygdala
- Indirectly via the cortex (long pathway)
- Directly (short route)
- Amygdala connects hypothalamus: bodily manifestations of feat
- Output: run/freeze
Where is sensory stimulation interpreted in?
sensory thalamus
When do we respond very quickly to a stimulus?
When the stimulus evokes fear and bypasses the cortex
Engage in fear without thinking, simply start feeling very agitated
what are the main circuits involved in fear conditioning?
- sensory areas - process the conditioned and unconditioned stimuli
- certain regions of the amygdala that undergo plasticity
Where does fear reponse start in the brain?
Amygdala
What is amygdala dedicated to detecting?
Emotional salience of the stimuli
What does amygdala activate?
Areas involved in preparation for motor function involved in fight or flight
Triggers the release of stress hormone and sympathetic nervous system
leads to bodily changes that prepare us to be more efficient in a danger
What brain regions is closely connected to amygdala and what are their roles?
- Hippocampus
- Prefrontal cortex
Help brain interpret the perceived threat
Involved in higher processing of context
Where does the conditioned stimulus flow from?
The lateral amygdala to the central nucleus of the amygdala
What controls defensive behaviour i.e. freezing?
Pathways from central nucleus of amygdala to downstream areas
what does the hypothalamus ochestrate?
- Freezing or fleeing response and all the physical manifestation
where is amygdala located in?
Medial temporal lobe
composed of number of different nuclei
What is lateral nucleus?
primary nucleus input of the amygdala
It receives input from the thalamus and the cortex which provide it with information of the sensory stimuli the animal is experiencing
What is the primary output nuclei of the amygdala?
Central medial nucleus
Projects to a number of different structures
Where does the central medial nucleus project to?
- Paraventricular nucleus of the hypothalamus and triggers release of stress hormone cortisol
- Lateral hypothalamus - stimulating the autonomic nervous system
- Periaqueductal grey matter - which in mice causes fear behaviours such as freezing
What happens when the downstream targets are coordinated?
The amygdala is able to produce many of the physiological changes associated with feeling of fear:
- Increased heart rate
- Sweating
- Dilation of the pupils
What is fear conditioning?
When an animal learns to fear something
What happens in a typical fear conditioning experiment?
- A mouse is given an unconditioned stimulus which is inherently negative such as a painful foot shock
- causes a natural unconditioned response - the expression of fear
- Also uses a neutral stimulus e.g. a sound which on its own produces no fear
- When the neutral and unconditioned stimuli are presented , the animal learns the association between the sound and the shock
- A neutral stimulus of the sound is then able to cause the fear behaviour itself without the shock
What is related to fear conditioning?
The concept of fear extinction
When does extinction occur?
When the conditioned stimulus of the tone is presented repeatedly without the unconditioned stimulus of the foot shock
The animal gradually learns that the sound no longer predicts a shock
The association is broken and the fear behaviour is no longer displayed
What is amygdala thought to be?
Primary area of the brain responsible for fear conditioning
How does amygdala participate in fear conditioning?
- The unconditioned stimulus of the foot shock travels to the spinal cord to the thalamus and cortex
- Which both project to the lateral nucleus of the amygdala
- The synaptic input from the unconditioned stimulus of the shock is strong enough to excite lateral amygdala neurons
- Activation of neurons in the central medial nucleus and produces a fear response
What happens when the neuron encoding the shock and the neuron encoding the sound fire together?
Synaptic plasticity occurs
This strengthens the synapse between the incoming neuron carrying information about the neutral stimulus of the sound and the lateral amygdala neurons
What does the lateral amygdala neuron do?
Excite central medial nucleus and produces feeling and fear
What are the neuroanatomical regions involved in anxiety disorders?
- Amygdala: the central fear centre
- Locus Coeruleus: Norepinphrine secretion - stimulated by active HPA axis
- Septohippocampal GABAERGIC system
Amygdala: The central fear centre
- Crucial for fear conditioning
2. Lesion in humans demonstrated pivotal for storage and processing of emotional memories
Locus coeruleus: Norephinephrine secretion
LC stimulation generates panic attack
LC blockade decreases panic attacks
Septohippocampal GABAERGIC system
- Mediate anxiety and vigilance
- High concentration of GABAergic neurons and receptors
- Directly connected to LC
What does the stimulation of the stress response engage?
Locus Coeruleus
Generating excessive response to a fear stimulus
Within a non-clinical population, where will there be differences in?
presentation of certain phenotypes
Who tends to have a larger amygdala?
Healthy children and adults with higher anxiety levels
What exhibits anxiety-related changes across the human adult lifespan?
Intrinsic functional connectivity between amygdala and multiple cortical networks
What is high-level trait anxiety predicted by?
Low-level global amygdala connectivity
What demonstrated anxiety-related changes of connectivity with left amygdala?
Somatomotor and dorsal attention networks
What had changes of connectivity with the right amygdala?
Frontoparietal control and ventral attention networks
What contributes to individual differences in anxiety behaviours?
Both low-level sensory networks and high-level associative network
What varies with individual’s level of anxiety?
Amygdala response to threat-related stimuli located outside the current focus of spatial attention
What leads to differential activation of amygdala?
stimuli with different objective levels of threat
What is consistent with the most previous fMRI studies of conscious perception of threatening stimuli?
consciously processed fearful faces selectively activate the dorsal but not the basolateral amygdala.
Where is the activation of amygdala altered in?
Abnormal anxiety
What is the consequence of people with anxiety?
The amygdala will be much more rapidly reactive to fearful stimuli
What is associated with lifespan anxiety?
The number of synaptic connection of amygdala with neurons in the cortex
When is it more likely that an individual will experience anxiety?
The more connection that exist between amygdala neurons and cortical neurons
What showed a positive correlation between ipsilateral amygdala iFC and anxiety?
An area adjacent to left lateral occipital, parietal, and superior temporal cortex
Who had stronger iFC of the left amygdala correlated with higher level of trait anxiety
The right posterior central area
Whereas an inverse correlational profile existed for the left dorsal lateral prefrontal cortex
What are the neurotransmitter thereoies of anxiety?
- Norepinephrine
- Serotonin
- GABA
What is norepinephrine?
Excess leads to excessive activation of cortex
NE reuptake inhibitors such as tricyclic antidepressant that block NE are effective anti-anxiety treatments
What is NRI associated with?
down-regulation of beta adrenergic receptors
What are beta adrenergic agonist and antagonist?
Agonist - Anxiogenic
Antagonist - Anxiolytic
What does stress paradigms generate?
Hypersecretion of NE
What is serotonin role?
- Complex
2. 5-HT can be anxiolytic and anxiogenic
For serotonin, what is effective anti-anxiety treatment across disorders?
SSRI
What are effective in some anxiety disorders?
Serotonin tricyclic antidepressant
What does Benzodiazepine (BZ) bind to?
GABA-A receptor
enhance GABA activity
potent anxiolytic
What does other GABA-receptor modulators (alcohol) have?
Anxiolytic effects
What is observed in brains of anxious disorders?
Reduction of BZ receptor
What enhanced anxious behaviours?
GABA-A/BZ receptor
What does benzodiazepine act as?
GABA-A allosteric modulator
What does BZ potentiate when it binds to its site?
Inhibitory action of GABA and produce:
- Sedation
- Sleep
- Anxiolysis
- Anticonvulsant activity
How is anxiety treated?
Anxiolytics
What are the drugs used to treat various anxiety disorder?
- Benzodiazepine
- Tricylic antidepressant
- Monoamine oxidase inhibitors
- Selective serotonin reuptake inhibitors
- Buspirone
What are examples of benzodiazepine, what disorders?
- Valium
- Xanax
- GAD
- PTSD
- Panic disorder
What are examples of tricyclic antidepressant?
- Tofranil
- Aventil
- Panic disorder
- GAD
- OCD
- PTSD
What are examples of monoamine oxidase inhibitors?
- Nardil
- Parnate
- Social phobia
- Panic disorder
What are examples of SSRI?
- Prozac
- Zoloft
- Paxil
- Social phobia
- Panic disorder
- OCD
- PTSD
What are examples of Buspirone
- BuSpar
- GAD
- Panic disorder
- OCD
What does anxiety disorders have?
Heterogenous origin
Where did most of the abundant research on PTSD actually come from?
Vietnam veterans
30% of veterans that came back from war experienced PTSD
What does PTSD have?
one of the highest incidence of suicide among all of the mental illness
What is PTSD?
A form of anxiety occurring after exposure to a traumatic event
What are examples of traumatic events?
- War
- Natural disaster
- Terrorist attacks
- Physical assault
- Rape
- Child abise
- Car accidents
What is PTSD characterised by?
- Increased physiological reactivity to reminders of trauma
- Sleep disturbances/nightmares
- Flashback to the traumatic event
- Avoidance of cues associated with trauma
- Numbing of emotional responses/detachment
What does imaging studies show?
High levels of responsiveness of amygdala to trauma cues
- Less activity in anterior cingulate and medial prefrontal cortices
What does PTSD cause?
- Dysregulation of HPA axis
- Low cortisol
- High CRH
- High catecholamine
What are the current pharmacological approaches for PTSD therapy?
- Use of benzodiazepine
2. Beta-adrenoceptor blockers
What does behavioural therapy include (PTSD)?
- Exposure based therapy in which an individual is exposed to a reimagining of the original trauma/ a cue associated with the original trauma in the absence of an aversive outcome
What is the therapeutic benefit in targeting epigenetic mechanism for PTSD therapy?
- Infralimbic medial prefrontal cortex to improve strength and persistence of extinction
What is a region linked specifically with memory extinction?
Infralimbic medial prefrontal cortex
What does histone acetyltransferase add?
Acetyl groups of histones, generally associated with relaxing wound DNA
What does HDAC do?
Remove these acetyl groups
What histone methyltransferase (HMT) do?
Add methyl groups to histone, generally associated with tightening wound DNA
What does HDM do?
Remove those methyl groups
What does DNA methyltransferase (DNMT) do?
Add methyl groups to DNA, sometimes associated with DNA silencing
How does the animal learn to stop responding feafully to stimulus via sounds?
Accumulation of new memories
What can help PTSD sounds?
Extinction which is new learning
What can accelerates the process of new learning or extinction?
- Ketamine
2. Hallucinogenic
What requires de novo transcription?
Consolidation of emotional memories
What is required to convert transient short term memory into persistent long-term fear memory (CREB activation)?
New gene transcription in the amygdala
What does memory consolidation also require?
Epigenetic changes (acetylation)
What promotes memory consolidation?
Enhancing acetylation
What are the consequence of PTSD?
- Lack of extinction of fear memories
- Reduced size amygdala in PTSD sufferers
- Hippocampus size predicts PTSD risk
What are the physiological reactions to PTSD?
- Flashbacks - reliving trauma
- Racing heart or sweating
- Bad dreams
- Having difficulty sleeping
- Frightening thoughts
- Feeling tense
- Having angry outburst
What does virtual reality run on ?
Commodity-level personal computers and provide interactive, immersive experiences and scenarios that open many doors for psychological research and behavioural health applications
What can VR provide?
a way to immerse users in stimulations of the traumatic experience
the clinician can precisely control the scene’s emotional intensity and customize the pace and relevance of the exposure for the individual patient
What is the main role of virtual reality?
Re-learning to ‘‘extinguish’’ emotional memory as therapeutic strategy to treat PTSD
What mediates the formation of new memories?
The use of histone de-acetylase inhibitors (HDAC) such as:
- Valproic acid
- Lithium
