LECTURE 17 - anxiety and depression Flashcards

1
Q

What are the 3 main types of mental health conditions?

A
  • anxiety disorders
  • depression
  • bipolar

last 2 are disorders of MOOD or ‘affect’ e.g. affective disorders
- not disorders of thought (those are psychoses)

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2
Q

What is anxiety disorder?

A

‘An inappropriate, or excessive, anticipatory manifestation of the fear response, often to a stressor’

  • defensive behaviours
  • autonomic reflexes
  • corticosteroid secretions
  • -ve emotions
  • -> interference with normal life
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3
Q

What are the different types of anxiety disorder?

A

General anxiety disorder
- somatic & autonomic effects: restlessness/ agitation, tachycardia, sweating, sleep disturbance

Others
- Phobic anxiety
- Panic disorder
=> useless to clump them together as psychopathology is not the same

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4
Q

What is the Hypothalamic-Pituitary-Adrenocortical (HPA) axis?

A

Hypothalamus releases CRF (corticotropin-releasing factor) –> anterior pituitary releases ACTH –> adrenal gland –> releases cortisol to inhibit hypothalamus releasing CRF (-ve feedback, turns itself down)

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5
Q

What happens to the HPA axis in an anxiety disorder?

A

Anticipatory (stressor not necessary)
Could be due to
- amygdala
- hippocampus

Upsetting normal balance of activity affects -ve feedback loop
Balance between amygdala and hippocampus somehow causes hyperactivity - unsure how

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6
Q

How are anxiety disorders treated?

A
  • psychological treatment e.g. phobias, neuroplastic change can sometimes be reversed
  • pharmacological interventions- very diverse
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7
Q

What are benzodiazepines?

A
  • anti-anxiety drugs

- e.g. diazepam, nitrazepam

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8
Q

How do benzodiazepines work?

A
  • target GABAa receptors
  • binds to allosteric (modulatory) sites
  • increased GABA infinity –> increased Cl-
  • hyperpolarisation due to Cl- = less activation
  • however there are GABAa receptors everywhere in the brain so drugs may not affect place we want it to
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9
Q

What are the useful effects of benzodiazepines?

A
  1. reduction in anxiety and aggression - anxiolytic
  2. sleep inducing - hypnotic
    => pharmacokinetic properties of drugs important, want a long duration of action
    diazepam and flurazepam last a long time and have a high metabolite 1/2 life
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10
Q

What are the problems with benzodiazepines?

A
  • sedation
  • acute overdose
  • -> profound sedation
  • -> with alcohol = serious respiratory depression

Long term use
- tolerance (‘tissue tolerance’), receptors stop responding how they used to
- dependence: leads to withdrawal –> increased anxiety, tremor, seizure, insomnia, depression
may be long-lasting therefore

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11
Q

What are novel anxiolytics?

A

5-HT(1A) partial agonists

  • busprione, precise mechanism unclear, slow to act (1-2 weeks)
  • assume some change in circuitry occurs in this time

effects of busprione

  • no sedation/ motor impairment
  • non-addictive, without withdrawal effect
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12
Q

What other drugs can be used to treat anxiety disorders?

A

B-adrenoceptor antagonists

  • reduces somatic symptoms of anxiety e.g. tremor, palpitations, sweating etc
  • used for situational phobias e.g. stage fright
  • works in periphery so alleviates symptoms not cause

Anti-Depressant (AD) drugs e.g. serotonin-selective reuptake inhibitors (SSRI)
=> questions if there is a link between anxiety and depression

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13
Q

What is Major Depressive Disorder (MDD)?

A
  • ~20% experience during lifetime
  • Symptoms
    • misery, despair, loss of motivation, appetite, suicidal thoughts
  • reactive (75%) e.g. bereavement vs endogenous (25%), something occurring in circuity
  • neurobiology not understood as well as neuropharmacology
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14
Q

What is the history of MDD?

A

Monoamine Theory of Depression: depression is due to hypoactivity at monoaminergic (NA and 5-HT) synapses in brain

Evidence for:
- ADs increase monoamine levels in brain rapidly in some animals

Evidence against:

  • ADs take >1-3 weeks to work in people
  • amphetamine and cocaine affect monoamines but neither are ADs
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15
Q

How is MDD treated?

A
  • psychotherapy
  • electroconvulsive therapy (ECT)
  • antidepressant drug classes:
    1. Monoamine oxidase inhibitors (MAOIs)
    2. Tricyclic antidepressants (TCAs)
    3. SSRIs
    4. Newer antidepressants
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16
Q

Monoamine oxidase inhibitors (MAOIs)

A
  • immediate effect = euphoria
  • true AD action - 4 weeks
  • examples: Moclobemide - reversible binding, MAO-A selectively increases 5-HT
  • unwanted effects:
    • unmetabolsited tyramine from diet (e.g. fermented things such as red wine, cheese, yeast)
    • displaces NA from vesicles in sympathetic neurones (e.g. increased heart rate)
    • anti-muscarinic effects
    • alpha-1 antagonism
17
Q

Tricyclic antidepressants

A
  • e.g. amitriptyline, imipramine
  • slow onset
    Mechanism
  • 5-HT/NA reuptake inhibition
    Unwanted effects
  • anti-muscarinic
  • sedative (H1 antagonism)
18
Q

SSRIs

A
  • e.g. fluoxetine (Prozac), paroxetine (Seroxat), Citalopram
    Mechanism
  • immediate increase in synaptic levels 5-HT
  • 2-4 weeks delay due to clinical effect
    Unwanted effects:
  • better than MAOIs and TCAs
  • age of patients impacts how useful they are and side effects
19
Q

Newer drugs

A
  • various uptake/ receptor mediated effects for 5-HT, NA, dopamine
  • but there is still a delay to action
20
Q

What is the network hypothesis of depression?

A
  • new theory to understand MDD
  • MDD –> increased [CRF] and [cortisol] in CSF
  • reversed by successful AD
  • shows some link between 5-HT and HPA axis
  • suggests somehow hyperactivity/ sensitisation of neuroendoricne stress response can lead to depression

Perhaps chronic stress –> anxiety disorder –> depression

21
Q

What is the mechanism of the network hypothesis?

A

Chronic stress

  • changes in hippocampus
  • -> decreased glucocorticoid receptors and BDNF (important for synapse formation)
  • -> decreased neurogenesis (new neurone production) and neuroplasticity

AD changes monoamine which restores ability for neuroplasticity and neurogenesis
- could explain delay in effect as restoration and formation of new neurones has to happen

22
Q

Do AD drugs work?

A
  • ~30% of patients don’t respond
  • trial and error required
  • pharmecogenomics - personalised medicine

Future developments

  • linking MA and neuroendocrine dysfunction
  • requires increased understating of neurobiology: neuroplasticity, neurogenesis and role of BDNF
  • hard to produce new drugs as difficult to evaluate efficacy
  • -> animal models not that useful as can’t ask how they feel
  • -> clinical trials difficult: slow onset of action, mood is variable, high placebo effect
  • -> finding new targets/ drugs is difficult