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Psychology & Neuroscience of Affective Disorders > An introduction to the psychopharmacology of mood disorders > Flashcards

An introduction to the psychopharmacology of mood disorders Flashcards

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1
Q

What is the function of a modulatory neuron?

A

Changes the effects of other neurotransmitters or second messenger systems

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2
Q

How do mood disorder drugs act?

A

Altering brain function:

  • change neurotransmitter function
  • mimic neurotransmitters (agonist)
  • block receptors (antagonist)
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3
Q

What are agonist drugs?

A

Drugs that mimic neurotransmitters

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4
Q

What are antagonist drugs?

A

Which block receptors

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5
Q

What is the main excitatory neurotransmitter?

A

Glutamate

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6
Q

What is the main inhibitory neurotransmitter?

A

GABA

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7
Q

What are the monoamine neurotransmitters?

A
  • Dopamine
  • Serotonin (5-HT)
  • Noradrenaline
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8
Q

What are the targets of monoamine drugs in mood disorders?

A

> Serotonin system

  • SSRI and SNRI antidepressants
  • second generation antipsychotics -> 5HT receptor actions

> Dopamine system
- second generation antipsychotics - D2 and D3 blockade

> Noradrenaline system
- SNRIs (Venlafaxine, Duloxetine)

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9
Q

What is the target of Ketamine and its action?

A
  • Targets glutamate system
  • Blocks NMDA Glu receptor
  • Shows promising efficacy in improving mood in patients with depression
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10
Q

What is the target of benzodiazepines and valproate?

A

GABA system

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11
Q

What is the target of the mood stabilisers lithium, valproate and carbamazepine?

A

Second messenger systems

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12
Q

What are the main discoveries in the history of the psychopharmacology of mood disorders?

A

> 1940s: Electroconvulsive therapy

> 1950s: lithium

> 1960s: First generation antidepressants: MAOIs, MARIs

> 1980s: Anticonvulsants (Carbamazepine, Lamotrigine, Valproate)

> 1990s: Second generation anti-depressants

> 2000s: Next-generation antipsychotics (Quetiapine, Olanzapine, Clozapine, Asenapine, Aripiprazole)

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13
Q

Why is serotonin of interest in mood disorders?

A

> Lowering serotonin levels -> induces depression

> Increasing serotonin levels -> can produce manic symptoms

> SSRI antidepressants and atypical antipsychotics all work in part by changing serotonin systems in brain

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14
Q

How does a normal serotonin system function?

A

> 5hT cell bodies are located in the caudal raphe nuclei (midbrain)

> Serotonin pathways have projections to the limbic system and subgenual cingulate

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15
Q

What are the important serotonin receptors related to mood disorders?

A
  • 5-HT 2

- 5-HT 1A

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16
Q

What is the action of selective serotonin re-uptake inhibitors (SSRIs) in the synapse?

A

Inhibit action of 5-HT re-uptake transporter

-> increases synaptic serotonin levels

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17
Q

What are the 5 types of SSRI antidepressants and their usual dosage?

A

> Citalopram (Cipramil): 20-40mg/day

> Escitalopram: 10-20mg/day

> Sertraline: 50-200mg/day

> Paroxetine: 20-50mg/day

> Fluoxetine (Prozac): 20-60mg/day

18
Q

What is the action of serotonin-noradrenaline reuptake inhibitors (SNRIs) in the synapse?

A

Inhibit action of 5-HT re-uptake transporter AND noradrenaline re-uptake transporter

-> increase serotonin and noradrenaline synaptic levels

19
Q

What are the three types of SNRI antidepressants and their usual dosage?

A

> Venlafaxine (Effexor): 75-375mg/day

> Duloxetine (Cymbalta): 60mg/day
- may increase dopamine levels in PFC

> Vortioxetine (Brintelix): 10-20mg/day

20
Q

How may the SNRI antidepressant Vortioxetine (Brintellix) improve cognitive impairment?

A
  • Blocks 5HT2, 5HT7 receptors
  • Stimulates 5HT1A receptor
  • > may improve cognitive impairment through 5HT7 blockade
21
Q

Why is dopamine relevant to mood disorders?

A

> Increasing synaptic dopamine levels can produce effect similar to mania

> Reducing synaptic dopamine levels improves manic symptoms but worsens depression

22
Q

What is the role of dopamine antagonist antipsychotics?

A
  • Main treatment for mania

- Used as mood stabilisers

23
Q

What is the role of dopamine in mania?

A

Mania is a result of increases in dopamine system

- particularly in nigrostriatal and limbic systems

24
Q

What is the action of dopamine antagonists in the mesolimbic pathway?

A
  • Lowers psychotic symptoms

- Lowers manic symptoms

25
Q

What is the action of dopamine antagonists in the tuberoinfundibular pathway?

A

Increase of prolactin secretion (via pituitary gland)

26
Q

What is the action of dopamine antagonists in the mesocortical pathway?

A
  • Increases negative symptoms
  • Increases cognitive dysfunction
  • May increase depressive symptoms
27
Q

What is the action of dopamine antagonists in the nigrostriatal pathway?

A

Impairs motor function (via substantia nigra pars compacta)

28
Q

What is the action of antipsychotics in the synapse?

A

Block dopamine postsynaptic receptors

-> decreased dopamine levels

29
Q

How are D2 antagonist antipsychotics used as mood stabilisers?

A

> Treat manic symptoms or prevent manic relapse

> Few antipsychotics treat depressive episodes in bipolar disorder

> Most antipsychotics block D2 receptors AND 5HT receptors (5HT2, 5HT1A, 5HT7)

30
Q

What is Quetiapine and its action?

A

Dopamine antipsychotic
- prevents both manic and depressive recurrence

  • blocks D2 and 5-HT2A receptors
31
Q

What is Olanzapine and its action?

A

Dopamine antipsychotic
- used to treat mania and bipolar depression

  • blocks D2 and 5-HT2A receptors, histamine H1 receptors, and the alpha-1 receptor
32
Q

What is Aripiprazole and its action?

A

Antipsychotic dopamine stabiliser
- prevents manic relapse

  • blocks D2, 5-HT1A, and 5-HT2A receptors
33
Q

What is the main target of benzodiazepines?

A

GABA-A receptor binding site

- main inhibitory system

34
Q

What are benzodiazepines used for?

A

Short term treatment of anxiety disorders

  • e.g. Diazepam, Clonazepam
35
Q

What are Z type hypnotics used for?

A

Short term treatment of sleep impairment
- through GABA-A binding site

  • e.g. Zopiclone, Zolpidem
36
Q

What is Sodium Valproate used for?

A

Mood stabiliser

- act in part through changing GABA levels

37
Q

What are second messenger systems?

A

Intracellular signalling molecules that are activated when neurotransmitter binds to G-protein coupled receptors

  • e.g. cyclic AMP, Inositol triphosphate
  • actions include increasing neurotransmitter release
38
Q

Why are second messenger systems important?

A

> Many drugs for mood disorders may act by altering second messenger systems

  • lithium
  • sodium valproate
  • carbamazepine

> Effects of these drugs on neurotransmitter release and other neuronal functions remain poorly understood

39
Q

What is the effect of mood disorder drugs on second messenger systems?

A

Inositol depletion hypothesis and bipolar disorder:
- medication blocks transfer of Inositol into neuronal cells

  • Lithium and Valproate may affect the activation of second messenger systems within neuron
40
Q

What is lithium and its role in mood disorders?

A

One of the most effective mood stabilisers
- prevents manic recurrence

  • less effective against depression
  • as monotherapy it’s probably effective for a minority of patients
  • levels greater than0.6mmol/L generally needed in prophylaxis may benefit patients with predominantly manic symptoms
  • reduces risk of suicide
41
Q

What is prophylaxis?

A

Measures designed to preserve health and prevent spread of disease

42
Q

What is the currently observed action of lithium in the brain?

A
  • Adjusts neurotransmitter balances
  • Adjusts basal and/or stimulated fluctuations in second messenger and protein kinases
  • Protects neurons from toxic insults
  • Modulates expression of specific genes
  • Modifies cytoskeletal function
  • Adjusts basal and/or stimulated fluctuations in transcription factors

Psychology & Neuroscience of Affective Disorders (16 decks)

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