Anxiety and Stress Treatment Flashcards
What is the amygdala and functions?
- series of nuclei
- involved in integrating the fear
response - limbic system
What happens when an amygdala is removed from the brain?
- loss of phobia of spiders
- loss of fear/inhibitions
Key Inputs to the Amygdala:
What is the role of the hippocampus in the regulation of anxiety?
by relating fearful memories to the current context
if abnormal function may generate fear in response to non-threatening stimuli
Key Neurobiological Stress Responses:
Activation of HPA Axis in Fear:
- amygdala activates the
hypothalamus - hypothalamus releases
corticotrophin releasing hormone,
(CRH) which acts on the pituitary
gland - pituitary releases
adrenocorticotropic hormone
(ACTH) which acts upon adrenal
glands - adrenal cortex releases cortisol
- cortisol is a glucocorticosteroid
which will ultimately release
glucose into the bloodstream in
response to the fear
HPA Axis:
Regulation of the HPA Axis:
negative feedback loop
cortisol directly feedback to hypothalamus and pituitary
cortisol acts on the hypothalamus also feedback to control cortisol levels
Activation of the Locus Coeruleus:
- amygdala activates locus coeruleus
- locus ceoruleus activation releases
noradrenaline - fight or flight response
Noradrenaline Pathways:
Amygdala and hippocampus respond to which neurotransmitter systems (3):
- noradrenergic
- serotonergic
- GABA
Noradrenergic Systems that affect that Hippocampus and Amygdala:
- origin
- effect
- originate in locus coeruleus
- increase arousal and anxiety
Serotonergic (5-HT) Systems that affect the Hippocampus and Amygdala:
- origin
- effect
- raphe nuclei
- signals presence of threat
- restrain associated behaviours
GABA System that affects the Hippocampus and Amygdala:
- origin
- effect
- distributed widely through the
brain - reduce anxiety
Noradrenaline involvement in Anxiety:
- increased noradrenaline in
prefrontal cortex found in anxiety
and PTSD - impaired cognitive function
- some adrenergic receptor
antagonists improve stress induced
cognitive impairment
Serotonin and Anxiety:
- arise from raphe nuclei
- drugs increasing serotonin levels
effective in treating both anxiety
and depression (SSRIs)
Serotonin and Anxiety:
Why SSRIs help with balancing pathways?
- noradrenaline increased in stress
- serotonin decreased in stress
- SSRIs increase serotonin in
synapses, hence push the shifted
balance back to normal
Some antidepressant that are effective in depression and anxiety increase reuptake both serotonin and noradrenaline.
Why do they not make people with depression more anxious?
- actions of SSRIs and SNRIs are
complex; delayed onset of action
suggests neuroadaptive changes
eg complicates - baseline activity vs reactivity of
noradrenergic systems - complex array of adrenoreceptors
and actions of these receptors
GABA and Anxiety:
- drugs increasing GABA activity
decrease anxiety - partial agonist: alcohol
- indirect agonist: barbiturates,
benzodiazepines - drugs decreasing GABA activity
increase anxiety - antagonist: flumazenil
- could anxiety be associated with
fewer GABA (A) receptors - endogenous neuromodulator
blocking benzo site at GABA (A)
receptor
GABA and Panic:
- patients with panic disorder have
fewer benzopdiazepine binding
sites - indicates a lack of sufficient
inhibitory control via GABA in
cortical and limbic regions to
suppress inappropriate fear
response and then panic attack
Functional Neuroanatomical Changes in Anxiety:
- amygdala: reduced volume,
hyperactivity - hyperactivity of thalamus
- overactivity of insular cortex in
response to threat - reduced volumes in anterior
cingulate cortex and prefrontal
cortex: areas important for
conscious threat appraisal and loss
of frontal-limbic regulation
processes - hippocampal changes
Chronic Stress and the Hippocampus:
- chronic activation by cortisol
- increases Ca2+ into neurons
- excitotoxicity results in cell
death
- damage to the hippocampus
means it cant feedback to limit
cortisol production - some anxiety disorders may result
from:
- diminished activity of the
hippocampus
- loss of feedback to amygdala
- inappropriate fear response
**reduced hippocampal volume in PTSD and in chronic stress in animals
Microscopically: fewer large pyramidal cells
Neurobiology of PTSD:
Neuroanatomy of PTSD:
Neurobiology of Phobia:
- hyperactivity of amygdala on
presentation of feared stimulus:
decreases with successful
treatment - anticipation of phobic stimulus:
activates the anterior cingulate
cortex - failure to activate cortical regions
that regulate limbic system:
ventromedial prefrontal cortex
Neurobiology of OCD:
- associated with conditions
affecting basal ganglia: Tourette’
syndrome, encephalitis lethargica,
sydenhams chorea - functional changes in neural
networks:- cortico-striatal-thalamo-cortical:
involves dopaminergic pathways - hyperactivity in head of caudate
nucleus, which can be reduced
by SSRIs and psychological
therapy
- cortico-striatal-thalamo-cortical:
Anxiety: Management: General Principles:
CBT:
- strong evidence across range os
psych disorders - involves talking about thoughts,
feelings and behaviour - focus is on maladaptive thinking
and behaviour
Anxiety Disorders: Phrmacotherapy:
- antidepressants: SSRIs; 6 months
for full effect - benzodiazepines: short term, avoid
when possible, high risk of
dependance, tolerance
not prescribed in primary care:
- buspirone: acts on 5-HT receptors,
not first line - pregablin: anticonvulsant,
controlled drug - combinations of antidepressants
or augmentation with other
medications; evidence less solid
GAD Diagnosis Timeline and Effect on Symptoms:
- only diagnosed at symptoms have
been present for 6 months - symptoms are already chronic at
the time of diagnosis
Panic disorder: Management:
- relies on general principle of
anxiety disorder management - psychoeducation re
hyperventilation - CBT will focus on cognition and
behaviours related to panic attacks
Specific phobia: Management:
- CBT based on graded exposure
- benzo short term used for
situational anxiety, till CBT
Social Anxiety Disorder: Management:
- ideally specialist CBT
- Some evidence for weekly
psychodynamic psychotherapy (6
months) - SSRIs may be effective
OCD: Management:
- CBT focused on obsessions and
compulsions - medication: SSRI, clomipramine
(tricyclic antidepressant) (not first
line) - no response to treatment -> mdt
review of all biopsychosocial
interventions -> consider
antipsychotic medication
PTSD: Management:
- general support if symptoms last
<4 weeks and not severe - consider screening for PTSD 4
weeks after major disorder - First line: specialist psychological
therapy: CBT, EMDR (eye
movement densitisation therapy) - Second Line: antidepressants
- Specialist: combinations of
medication including an
antipsychotic
