NEUR 3594 Exam 1 - Anxiety and Trauma 2

What is true of anxiety disorders running in families

Anxiety disorders moderately run in families, first degree relatives of someone with disorder are 4 to 6 times more likely to develop disorder

What were early candidate gene studies focused on

Neurotransmitter systems, which were mostly inconsistent results and false positives

What was the scale GWAS for ADs

A large scale GWAS for AD was revealed, about 50 significant loci were associated with MDD or neuroticism

What neurotransmitter signaling is said to be involved with the mechanisms underlying AD genetic risk

GABAergic signaling

What was the scale GWAS for PTSD

A large scale GWAS identified about 43 genes to be likely causal, these neurons were apart of neural networks, synaptic plasticity and immune processes

What have animal models done in regards to HPA axis

Revealed roles of genes in HPA axis like FKBP5

What is the HPA axis

Hypothalamus-pituitary-adrenal axis

What is released from the hypothalamus in the HPA axis

Corticotropic releasing hormone (CRH) and AVP

What is released by the pituitary in the HPA axis

Adrenocorticotropic hormone (ACTH)

What is released by the adrenal glands in the HPA axis

Cortisol (glucocorticoid)

What type of feedback loop is the HPA axis

Negative feedback loop at the pituitary and hypothalamic level (cortisol decreases CRH and ACTH secretion)

What do FKBP5 do in the HPA axis

Modulate the axis and stress response by reducing receptor sensitivity to cortisol via regulating transcription (FKBP51)

How is the FKBP5 process moderated

By a SNP

How do cortisol and FKBP5 regulate HPA axis to stressors

By regulating cortisol effects, FKBP51 can indirectly regulate the sensitivity of the HPA axis to stressors

What is the diathesis stress model

Diathesis (gene predisposition) + stress (environmental stressor) = development of disorder (stronger diathesis=less stress needed to produce disorder)

What is face validity

If an animal model of a disease looks similar to the human condition, whether behaviorally or in physical appearance, the model has good face validity

What is construct validity

Sometimes an animal model of a disease starts with the same pathological changes in the brain that observed in human patients, this means they have good construct validity

What is predictive validity

If the animal can be used to predict whether the therapy/ treatment would be effective in treating humans with the same condition, it has good predictive validity

What are the validated tests for assessing anxiety and excessive fear in rodents

Pavlovian fear conditioning, acoustic startle, light startle, predator odor, looming, conditioned taste aversion, Vogel drinking conflict, and Geller-Seifter operant conflict

What is an elevated plus maze

Measures time spent in open vs enclosed arms. Mice with higher anxiety spend more time in the enclosed arms

What is the light-dark box

Measuring time spent in light vs dark sides. Highly anxious mice spend more time hiding in the dark compartment

What is marble burying

Mice naturally tend to dig in new environments and burry unfamiliar objects. Mice that exhibit anxious repetitive behaviors bury more marbles than normal.

What is open field assessment

Measure of locomotor activity. More anxious mice spend more time near the walls and have more grooming and rearing behaviors

What is the social interaction assessment

Measure of social behaviors. Anxious mice may exhibit less sniffing and chasing and increased avoidance of the stranger mouse

SLIDE 15+ 16!!!

What is fear generalization

Fear response to initial CS start to generalize to stimuli that are unique yet perceptually or thematically related to the CS

What’s an example of a conditioned stimulus

Bell or tone

What’s an example of a unconditioned stimulus

Food or shock

What’s an example of a conditioned response

Salivation or freezing

What is avoidance behavior

Active (deliberate escape) or passive (freezing)

What is fear extinction

Diminishing the CR after repeated presentations of the CS without the US (don’t unlearn the fear memory)

What does the curve of acquisition show

The CR gets stronger through repeated association of the CS and US

What does extinction show

The CR becomes weaker as just the CS is presented on its own

What does spontaneous recovery show

The CR can reappear after a long period of time

How may anxiety arise from threat conditioning

Via enhanced fear-response to stimulus and reduced fear extinction

What parts of the brain are involved in threat conditioning

Amygdala, medial prefrontal cortex, and the hippocampus

What is exposure therapy

A cognitive behavioral therapy used to treat many anxiety disorders

What brain regions are involved in the threat-responsive circuitry

mPFC, hippocampus, amygdala, insula, stria terminalis

What are the outputs of the threat-responsive circuitry

Avoid, freeze, flee, flight

What is reactivity

Type and magnitude of response to emotion-eliciting events. Involves detection and allocation of attention to stimulus

What do disturbances have to do with reactivity

Disturbances may include heightened negative emotions (irritability) or diminished positive emotions (numbness), (in addition to fear and anxiety)

What areas of the brain are involved in reactivity

Involves large number of cortical and sub cortical areas

What is regulation

Attempts to influence or modulate the intensity, duration, and type of emotion experienced (can be implicit emotion regulation)

What brain regions are involved in defensive learning and emotional processing

Extended amygdala (amygdala and bed nucleus of stria terminalis), insula, periaqueductal gray, hypothalamus, hippocampus, prefrontal cortex

In humans what is the anxiogenic pathway for defensive learning and emotional processing

From the dmPFC to the amygdala

In humans what is the anxiolytic pathway for defensive learning and emotional processing

From the vmPFC to the amygdala

In rodents what is the anxiogenic pathway for defensive learning and emotional processing

From the pre limbic cortex to the amygdala, which goes to the ventral hippocampus, from the pre limbic cortex to the ventral hippocampus, and from the bed uncles of the stria terminalis to the ventral tegmental area

In rodents what is the anxiolytic pathway for defensive learning and emotional processing

From the infra limbic cortex to the amygdala, from the bed nucleus of the stria terminalis to the lateral hypothalamus, BNST to amygdala, BNST to ventral tegmental area, and BNST to parabrachial nucleus

What is the insula

Represents bodys internal state and interoception. It is involved in emotional reactivity and regulation

What is interoception

The sense of the overall physiological condition of the body as well as feeling states and emotional awareness

What is the amygdala

Located within the medial temporal lobes and is associated with fear and anxiety. Activated in response to appetitive and aversive emotional stimuli

What is the basolateral amygdala

Primary input area that receives incoming sensory information from the thalamus and from the sensory and association cortices

What does the basolateral amygdala do

Evaluates and encodes the values of the threatening stimulus, responsive to both positive and negative emotional stimuli, important for fear conditioning and extinction

What is the centromedial amygdala

More selective for negative emotional stimuli (particularly fear and threat) crucial for conditioned fear

Why is the amygdala critical

For defensive learning and emotional reactivity

Amygdala activity and emotional regulation

Lowered amygdala activity with successful emotional regulation (largely mediated by prefrontal control areas)

Amygdala and lateral hypothalamus connection

Sympathetic activation (increased heart rate and blood pressure, pupils dilate)

Amygdala and dorsal motor nucleus of vagus

Parasympathetic activation (ulcers, urination, defecation)

Amygdala and parabrachial nucleus

Increased respiration (panting, gasping for breath)

Amygdala and VTA, LC, Peduncular pontine nucleus (PPN)

Activation of DA, NE, and ACh respectively (behavioral arousal and increased vigilance)

Amygdala and nucleus reticular

Increased reflexes (increased startle response)

Amygdala and periaqueductal gray

Cessation of behavior (freezing)

Amygdala and trigeminal & facial nuclei

Mouth open and jaw movements (facial fear expression)

Amygdala and paraventricular nucleus of hypothalamus

ACTH release (glucocorticoid release [stress response])

What does the bed nucleus of the stria terminalis do

For sustained and generalized fear response (diffuses threat), mediates hyper vigilance when threat is not imminent but possible

What does the prefrontal cortex do

Essential for emotional regulation

What does the ventral hippocampus do

Processes contextual information, binds together multimodal information, helps with fear generalization, discrimination, extinction, and decision making over avoidance or escape

Circuit organization in anxiety

Four step model in which environmental stimuli are detected, interpreted, evaluated, and responded to by succeeding levels of highly interconnected neural circuits and neuropeptides (many circuits and brain regions involved in anxiety pathology)

How do neuroimaging abnormalities vary in dlPFC in regulation

Decrease abnormalities in social anxiety disorder, decreased in generalized, decreased in panic disorder, and decreased in post traumatic stress disorder

What are treatments for anxiety, OCD, and PTSD

Pharmacotherapy (treatment with drugs), anti anxiety medication (SSRIs, benzodiazepines, and buspirone)

What does it mean to be a first line therapy

First method of action

What are some first line pharmacotherapy drugs

Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)

What are some second line pharmacotherapy drugs

Benzodiazepines, azapirones (buspirone), tricyclics, anticonvulsants, antihistamines, Beta blockers (acts on adrenergic receptors [NE,E])

What happens as CNS depressant dosage increases

As dose of benzodiazepines increases, the level of consciousness decreases, as is the case with CNS depressants (sedative hypnotics)

Why is GABA-induced inhibition for controlling excitability

GABA-induced inhibition is important for controlling the excitability of local circuits and it regulates the activation of the central nucleus of the amygdala

What are benzodiazepines in regards to GABA receptors

Positive allosteric modulators, that do not bind at the GABA site but at the benzodiazepine site

What effect do benzodiazepines have

They increase the affinity of GABA for its receptor and/or increase the frequency of channel opening when GABA is bound but do not have any effect in the absence of GABA

What is the effect of GABA and benzodiazepines together

GABA and benzodiazepines have a greater effect than just GABA alone

What effect do barbiturates have

Barbiturates are a positive allosteric modulators at the GABA r, they increase the affinity of GABA r for GABA, however they increase the duration of the opening of GABA activated Cl- channels rather than the number of openings

What do barbiturates do without presence of GABA

Barbiturates directly open the Cl- channel without GABA

What are neurosteroids

Drugs that enhance neuroactive steroids reduce anxiety and seizures, but produce sedation

What is buspirone

A partial agonist of the serotonin I A receptor that reduces anxiety and depression without sedation or mental clouding

What are the pros and cons of buspirone

No withdrawal symptoms or potential abuse, but has slow onset and cannot be used for alcohol or barbiturate withdrawal, insomnia, or seizures

What is cognitive behavioral therapy

Includes psychoeducation (self monitoring of thoughts), cognitive restructuring (by identifying errors in thinking and replacing them with evidence based thoughts), and behavioral exposure (approaching feared experiences)

What model can be used to describe the maladaptive processes that occur during mental disorders

The cognitive behavioral model of anxiety disorders

What are complementary and integrative health approaches

Mindfulness based approaches, exercise, and yoga