Neurobiology of affective disorders Flashcards Preview

202: Theme 3, Modulatory systems in psychiatry > Neurobiology of affective disorders > Flashcards

Flashcards in Neurobiology of affective disorders Deck (25)
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1

Environmental links to depression

Accumulation of stress--> HPA axis

Adverse childhood experiences
- History of maltreatment
- Affects HPA axis function

Past depressive episodes
- Affects PFC and hippocampus

2

Biological basis of major depression

Disruption in the Serotonin and noradrenaline system

Disruption of hypothalamal-pituitary-adrenal axis

Inflammation

3

Serotonin/ NA system and depression

5-HT and NA are reduced in depression

- Reduced 5-HT from Raphe nuclei
- Reduced NA from Locus Coerulus
- Reduced 5-HT transporters


Supported by anti-depressives drugs
- Reduced symptoms by affecting SRT and NA systems

4

HPA axis

Hypothalamic-pituitary-adrenal axis

Stress triggers release of hormones

1. Hypothalamus releases corticotrophin releasing hormone [CRH]
- Stimulates the release of adrenocorticotrophin hormone [ACTH] from the anterior pituitary

2. ACTH stimulates glucocorticoid release from the adrenal glands--> stimulates cortisol release

5

HPA axis and depression

Stress stimulates excess release of cortisol [from adrenal gland] via the HPA axis

Cortisol inhibits activity in the hypothalamus and hippocampus

Glucocorticoid receptors in the hypothalamus are altered, affecting the sensitivity to cortisol [lack of dexamethasone suppression]

6

Inflammation and depression

Increase in inflammatory markers thought to stimulate depressive symptoms.

Raised cytokine levels
- IL-6
- TNF-alpha

NF-kB--> decreases monoamine levels

7

Evidence for inflammatory mechanism behind depression

Chronic inflammatory disease show co-morbidity with depression

Administration of cytokines stimulate depressive symptoms

PET studies show microglial activation in brains with depression

8

Monoamine oxidase inhibitors
- Type
- Mechanism
- Examples

First generation antidepressant.

Mechanism: NON-selectively inhibits breakdown of monoamines--> SRT, NA, DA

Examples
Type A
- Phenelzine
- Tranylcypromine

Type B
- Selegiline

9

Monoamine oxidase inhibitors
- Side effects

Non-selectivity= affects wide range of systems

Dry mouth
GI constipation
Headache
Drowsiness
Insomnia
Dizziness
Hypertensive crisis due to food interaction

10

Tricyclic antidepressants
- Type
- Mechanism
- Examples

First generation antidepressant

Mechanism
-NON selective inhibition of monoamine re-uptake transporters

Examples:
- Amitryptiline
- Clomipramine

11

Tricyclic antidepressant side effects

Constipation

Orthostatic hypotension

Dry mouth

Drowsiness

Cardiac toxicity in overdose

12

SSRIs
- Type
- Mechanism
- Use/ treatment
- Examples

Selective serotonin re-uptake inhibitor
- Selectively inhibits serotonin re-uptake transporter

Can also be used to treat
- OCD
- PTSD
- Social/ general anxiety disorder

Treatment
- Slow titration due to prevalence of side effects in the initial treatment

Examples
- Fluoxetine
- Sertraline
- Citalopram
- Escitalopram

13

SSRIs
- Side effects

GI symptoms- nausea, diarrhoea

Headache

Irritability

Anxiety

Reduced libido and sexual dysfunction

14

SNRI
- Type
- Examples

Selective noradrenaline re-uptake inhibitor
- Second generation antidepressant

Examples:
- Venlafaxine
- Duloxetine

15

Venlafaxine
- Type
- Side effects

SNRI
- Antidepressant

Side effects:
- Nausea
- Vertigo
- Headache
- Insomnia

16

Alpha-2 and 5-HT2c antagnoist
- Function
- Example

Second generation antidepressant
- Modulate the release of serotonin and NA release

Example
- Mirtazapine

17

Mirtazapine
- Type
- Mechanism
- Side effects

Second generation antidepressant

Mechanism:
- Alpha-2 and 5-HT2c antagonist
- Modulates SRT and NA release
- Also a very potent antihistamine

Side effects:
- Drowsiness
- Sedation
- Hypotension
- Increased appetite
- Weight gain

18

Antipsychotics

Primarily increase action of dopamine
- D2/3 antagonists
- Also 5-HT action

Side effects:
- Extrapyramidal [haloperidol]
- Weight gain
- Glucose and lipid dysregulation
- Parkinsonism

19

Haloperiodol
- Action
- Side effects

D2/D3 antagonist
- Anti-psychotic
- Non-selective--> Extrapyramidal side effects

20

Aripiprazole
- Action

DA partial agonist

Atypical antipsychotic
- Treats bipolar
- Major depressive disorder

21

Lamotrigine
- Type
- Action
- Use

Anticonvulsant
- GABA agonist
- Inhibits Na+ channels

Use
- Prevents depressive relapse
- Not effective as an anti-manic agent

22

Carbamazepine in bipolar

Very effective in preventing manic relapse
- Not as effective in maintaining treatment

23

Treatment of acute manic episodes

DA antagonists
- Haloperidol
- Olanzapine
- Risperidone
- Quetiapine

Valproate [not in child bearing women]

24

Buspirone
- Side effect

5HT1A partial agonist
- Treats anxiety disorders

Interacts with grapefruit

25

Typical antipsychotic side effects [Haloperidol]

EPS

Tardive dyskinesia