Lecture 49: Neurobiology of Anxiety Flashcards
What is the normal anxiety response?
Promotes optimal functioning (anxiety when you are trying to make it to class on time)
What is abnormal anxiety response?
Interferes with functioning
How do you want to think of anxiety?
Continuum of anxiety
Worry Panic
Worry is least anxious
Panic is most anxious
What is the Yerkes-Dodson Law?
Medium amount of arousal leads to highest performance…don’t want to be too worried or too relaxed
What axis regulates anxiety?
The HPA (hypothalamo-pituitary-adreno) Axis
What is the General Adaptation Syndrome?
Used for coping with stress
Sympathetic response (caused by release of Epi and NE from adrenal medulla)
Long term adjustments = mobilization of remaining energy reserves/conservation of glucose
Can lead to exhaustion phase where vital systems collapse
-exhaustion of lipid reserves
-inability to produce glucocorticoids
-failure of electrolyte balance
What are the different biological mechanisms of anxiety?
- Neurochemical
- Genetic
- Neuroanatomical
- neurofunctional
What regulates the neurochemistry of anxiety?
- Monoaminergic neurons with wide range
- Raphe nuclei = serotonin
- Locus coeruleus = NE
- some DA neurons
- GABA
What is the role of GABA in anxiety?
Two distinct types of GABA receptors? i. GABA-A is LINKED with anxiety -allows Cl- to enter cell -fast acting (ionotropic) Pentamer of 5 unites
What is the significance of GABA-A?
One type of GABA receptor
-linked with anxiety
-binds to barbiturate, steroid, ethanol and GABA lol
Can Inhibit anxiety when activated or deactivated?
What is the role of Serotonin in anxiety?
Synthesized In discrete brainstem nuclei in median/dorsal raphe
Drugs that block re-uptake of 5-HTs have positive results
-antidepressants = SSRIs
-also works on anxiety
More serotonin the better…
What is the role of Norepinephrine in anxiety?
Excessive sympathetic activation may produce dysfunctional arousal
Alpha 2 NE receptor is associated with anxiety/depression
What is the role of Dopamine in anxiety?
-seen in substantia nigra, ventral tegmental area
-involved in reward pathway (VTA, nucleus accumbens, cingulate)
Not much is known in relation to SAD, PTSD and OCD
What are the key points about the genetics of anxiety?
People who are more likely to be behavioral inhibition will be more anxious
Neuroticism
-predisposes to GAD
-associated with allelic variations in promoters region of serotonin transporter gene
- moderately heritable
What is neuroticism associated with?
Allelic variations in promoter in serotonin transporter gene
SMALLER amygdala and cingulate
Abnormal hippocampal and fronto-limbic activity
What is classical conditioning?
Pavlov’s dog…salivate when hearing bell
What is operant conditioning?
Reward, punishment and EXTINCTION
What is reinforcement?
Anything that increases likelihood of a behavior Positive reinforcers (doing something positive) Negative reinforces (removing aversive stimulus after response)
What is punishment?
Anything that decreases likelihood of a behavior
Positive punishment = presenting aversive stimulus after response
Negative punishment = removing positive stimulus after response (no TV)
What is the behavioral model for anxiety disorders?
Anxiety begins with classical conditioning
It is maintained through operant condition (negative reinforcement)
What is fear extinction?
Learning not to fear
-presenting conditioning stimulus WITHOUT unconditioned stimulus will lead to extinction (gradual process)
-important adaptation that can allow suppression of previous fear (kind of like OCD treatment)
It is NEW learning
It is NOT forgetting
-context dependent: fear response can still occur in contexts that are different from where extinction occurred
What is exposure treatment?
Fear memory is never “erased”
So competition between safety learning and fear learning is resolved by context
-contexts may include time, drug state, therapists presence, stimulus
It is important to conduct extinction training in MULTIPLE contexts
What happens to conditioned response as a result of extinction learning?
CR returns after rest period (after extinction training)
If extinction occurs in different environment than acquisition, putting animal back in orginal environment evokes CR again
Reinstatement of fear from US can reinstate CR
What are the key areas of brain involved in stress response?
Locus coeruleus (sympathetic activation Limbic system (Papez) Hippocampus, fornix, mammillary bodies, thalamus, cingulate, amygdala/hypothalamus Integrated system -PFC -amygdala
What is the significance of Papez circuit?
Emotional representaitons from thalamus to
1. Cortex (stream of thinking)
2. Hypothalamus (stream of feeling)
Output from cingulate cortex allows for top-down control of emotional responses
-eg you’re at a funeral so you shouldn’t laugh
What is connection between PFC and amygdala?
PFC can augment or inhibit amygdala response to stimulus
What do fearful expressions activate?
Amygdala…doesn’t require conscious recognition…subconscious stimuli processing
What is amygdala associated with?
Associated with fear in response to cue
-associated with fear in response to context
Amygdala associated with all types of fear
What is the hippocampus associated with?
Associated with fear in response to context
