Anxiety Disorders - Neurobiology, Neurochemistry & Treatment Flashcards by Hannah Wilkinson

What are the three divisions of anxiety disorders?

Continuous anxiety

Episodic anxiety

OCD

How well did you know this?

Not at all

Perfectly

Which part of the brain generates the fear response?

Amygdala

How well did you know this?

Not at all

Perfectly

What happens if you remove the amygdala?

Ps stop fearing things (such as spiders) that they were pathologically scared of before the surgery

How well did you know this?

Not at all

Perfectly

What are the three key sensory inputs to the amygdala in the brain?

Sensory thalamus
Somatosensory cortex
Anterior cingulate gyrus

How well did you know this?

Not at all

Perfectly

What role does the hippocampus provide to the amygdala?

Relays fearful memories to present contexts

How well did you know this?

Not at all

Perfectly

Which three main areas of the brain does the amygdala excite in response to a fear stimulus?

Lateral hypothalamus

Locus coeruleus

Periventricular hypothalamus

How well did you know this?

Not at all

Perfectly

What does the lateral hypothalamus do in response to fear stimulus (via the amygdala)?

Activates the SS

How well did you know this?

Not at all

Perfectly

What does the locus coeruleus do in response to fear stimulus (via the amygdala)?

Fight or flight response

How well did you know this?

Not at all

Perfectly

What does the periventricular hypothalamus do in response to fear stimulus (via the amygdala)?

Activates the HPA Axis

How well did you know this?

Not at all

Perfectly

Which part of the brain is responsible for the autonomic part of the acute stress response?

Lateral hypothalamus

How well did you know this?

Not at all

Perfectly

Which part of the brain is responsible for the behavioural part of the acute stress response?

Locus coeruleus

How well did you know this?

Not at all

Perfectly

Which part of the brain is responsible for the endocrine part of the acute stress response?

Periventricular hypothalamus

How well did you know this?

Not at all

Perfectly

How does the HPA Axis work?

Fear stimulus tiggers the amygdala

Amygdala activates the hypothalmus

Hypothalamus releases CRH (corticotrophin releasing hormone) –> pituitary gland

Pituitary gland releases ACTH –> adrenal glands

Adrenal cortex releases cortisol = stress hormone = inhibits the Hypothalamus and Pituitary gland

How well did you know this?

Not at all

Perfectly

Which two parts of the brain regulate the input to the Hypothalamus as part of the HPA axis? How do they both influence it?

Amygdala - stimulates the hypothalamus to release CRH.

Hippocampus - inhibits the hypothalamus from releasing more CRH.

How well did you know this?

Not at all

Perfectly

When will the hippocampus send inhibitory messages to the hypothalamus?

Hippocampus - has lots of glucocorticoid receptors - these are stimulated by release of cortisol from the adrenal cortex - stimulates the hippocampus to send inhibitory messages to the hypothalamus.

How well did you know this?

Not at all

Perfectly

Which part of the brain is responsible for the behavioural (fight or flight) response to stress?

What is it activated by?

What does it release?

Locus Coeruelus

Activated by the amygdala

Releases noradrenaline

How well did you know this?

Not at all

Perfectly

Where is the origin of the noradrenergic system? What is it responsible for?

Locus coeruleus

Increases arousal and anxiety. When fearful stimuli are received - locus coeruleus releases NOR throughout the brain.

How well did you know this?

Not at all

Perfectly

Where is the origin of the serotonergic system?

What can decreased levels of 5-HT cause?

Raphe nuclei

Decreased levels of 5HT can cause inappropriate fear and anxiety

How well did you know this?

Not at all

Perfectly

What role does GABA play in anxiety? How do benzodiazepines affect anxiety?

GABA reduces anxiety (inhibitory). Benzos modulate GABA receptors and also work to reduce anxiety

How well did you know this?

Not at all

Perfectly

Which three NTs in the brain are involved in fear and anxiety?

Noradrenaline
Serotonin
GABA

How well did you know this?

Not at all

Perfectly

What is increased amounts of noradrenaline in the prefrontal cortex associated with?

Impaired cognitive function

How well did you know this?

Not at all

Perfectly

Pharmacologically, what can we use to improve stress-induced cognitive impairment?

Adrenergic receptor antagonists - reduces the amount of noradrenaline binding in the PFC = improved cognitive function

How well did you know this?

Not at all

Perfectly

Where are the Raphe nuclei found?

In the brainstem

How well did you know this?

Not at all

Perfectly

Which drugs increase serotonin levels in the brain?

What are they used to treat?

Selective serotonin reuptake inhibitors (SSRIs)

Treat anxiety and depression

How well did you know this?

Not at all

Perfectly

How do noradrenaline and serotonin interplay in the brain? How can this be related to anxiety disorders in patient? What can be used to treat this?

Both NOR and 5HT have opposing effects in the brain and are often involved in fine balance for normal behaviour. If this balance is upset - e.g. too little 5HT - can cause fear response to inappropriate stimuli. SSRIs can push the balance back to normal levels.

What is the noradrenergic paradox?

The fact that some antidepressants which work increase reuptake of 5HT AND Nor = by increasing NOR amounts in brain it is thought that it should make Ps more anxious - HOWEVER this does not happen. Complicated reasons why, not not fully understood.

How do drugs that increase GABA affect anxiety?

They decrease anxiety

What is a partial agonist of GABA receptors?

Alcohol

What is an indirect agonist of GABA receptors?

Benzodiazepines Barbituates

In what was is it thought that GABA receptors can play a role in anxiety?

Thought that Ps with anxiety could have 1. Fewer GABA A receptors = less inhibition 2. There is an endogenous neuromodulator which blocks the benzodiazepines site on GABA A = means less inhibition occurs

What is the difference between using a benzodiazepine antagonist and a GABA antagonist?

Benzo antagonists - only work to negate the modulatory effect of the benzo - so GABA levels return to normal baseline. GABA antagonists inhibit the GABA receptors completely - therefore much reduce the GABA levels to below the baseline.

What did PET studies on benzodiazepine binding sites show?

That some Ps with panic disorder had fewer of the benzo binding site = does this mean that they had less inhibitory control via GABA?

How does neuroanatomy feature in anxious Ps?

Often seen with changes to their neuroanatomy - e.g. reduced volume & hyperactivity of amygdala, thalamus & hippocampus, anterior cingulate cortex & PFC Overactivity of insula cortex

How does chronic stress affect the hippocampus?

Chronic stress = chronic activation of the hippocamus This increase amount of calcium in the neurons = excitotoxicity & cell death = damage to hippocampus, loss of volume & loss of ability to limit cortisol production.

How has the hippocampus been viewed in Ps with PTSD?

Reduced in volume

Name 5 things seen in the neurobiology of PTSD?

- Dysregulation of HPA axis - Increased NOR - Decreased 5HT - Decreased GABA - Increased glutamate

What does dysregulation of the HPA axis mean for a patient with PTSD?

There will be abnormal stress and fear processing. Can cause hippocampus atrophy

What does increased noradrenaline mean for a P with PTSD?

Increased alertness, startle response, encoding of fear memories, inc pulse & BP

What does decreased 5HT mean for a P with PTSD?

Disturbs dynamic between amygdala and hippocampus - inc levels of NOR. Increases vigilance, startle, impulsive & memory intrusions

What does decreased GABA mean for Ps with PTSD?

Compromised inhibition of other systems

What does increased glutamate mean for Ps with PTSD?

Linked to derealisation and depersonalisation

What neuroanatomical changes are seen in a P with PTSD?

Reduced hippocampal vol (& activity) Increased activity of amygdala (hypervigilance & impaired discrimination of threat) Reduced volume of PFC (impairing executive function) Reduced anterior cingulate volume (inc fear responses)

Which area of the brain is seen to be hyperactive in Ps with fear phobia?

Amygdala

Anticipation of a phobic stimulus activates which part of the brain?

Anterior cingulate cortx

What role does the cortex play in phobia?

Failure to activate the cortical regions that regulate the limbic system (e.e ventromedial PFC) - means there is no rationality to the phobic response

What is seen functionally in Ps with OCD?

Functional changes in neural networks (cortico-striatal-thalmo-cortical path) and hyperactivity in caudate nucleus.

What conditions is OCD associated with?

Conditions which affect the basal ganglia (e.g. Tourettes, encephalitis lethargic & Sydenham's chorea)

What treatments are given to Ps at risk of anxiety or with mild anxiety?

Social prescribing Psychoeducation, problem-solving techniques, self-help & CBT

What treatments are given to Ps with moderate anxiety?

CBT or pharmocotherapy or both

What treatments are given to Ps with severe anxiety / unresponsive anxiety?

CBT + pharmocotherapy

What does CBT focus on and try to change/

Maladaptive thinking and behaviour

Which is the first line antidepressant used?

SSRIs

What is the minimum period of time that SSRIs should be used for?

6 months

Why is use of benzos avoided where possible?

High risk of dependance and tolerance

How long do symptoms have to be present in order to be diagnosed for generalised anxiety disorder? What does this mean?

6 months Symptoms are chronic by time of diagnosis

What are outcomes for generalised anxiety treatment like?

Relatively poor - 25% remission from secondary care. Tends to be chronic and fluctuating course.

How are panic disorders treated?

Same principles as anxiety disorders + Psychoeducation for hyperventilation CBT for panic attacks

How are specific phobias treated?

No real medication for these (poss benzos for immediate situation - e.g. flying). CBT inc graded exposure

What is graded exposure in CBT?

Gradual introduction of the feared stimulus - thinking about etc to actual introduction of the stimulus

How are social anxiety disorders treated?

Specialist CBT Psychodynamic psychotherapy SSRIs may be effective

How is OCD treated?

CBT - focussing on the O & Cs. Medication - SSRIs & poss Clomipramine If no response - may add antipsychotic

What is PTSD not treated before 4 weeks?

P may be suffering from acute stress reaction that may recover spontaneously.

What is the treatment for PTSD?

1st - Specialist psychological therapy - CBT & EMDR (eye movement desensitisation therapy). 2nd - Antidepressants Specialist = combination of drugs inc antipsychotics

What is the first line treatment for most anxiety disorders?

Psychological therapy