Neurobiology of affective disorders Flashcards
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
Biological basis of major depression
Disruption in the Serotonin and noradrenaline system
Disruption of hypothalamal-pituitary-adrenal axis
Inflammation
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
HPA axis
Hypothalamic-pituitary-adrenal axis
Stress triggers release of hormones
- Hypothalamus releases corticotrophin releasing hormone [CRH]
- Stimulates the release of adrenocorticotrophin hormone [ACTH] from the anterior pituitary - ACTH stimulates glucocorticoid release from the adrenal glands–> stimulates cortisol release
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]
Inflammation and depression
Increase in inflammatory markers thought to stimulate depressive symptoms.
Raised cytokine levels
- IL-6
- TNF-alpha
NF-kB–> decreases monoamine levels
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
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
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
Tricyclic antidepressants
- Type
- Mechanism
- Examples
First generation antidepressant
Mechanism
-NON selective inhibition of monoamine re-uptake transporters
Examples:
- Amitryptiline
- Clomipramine
Tricyclic antidepressant side effects
Constipation
Orthostatic hypotension
Dry mouth
Drowsiness
Cardiac toxicity in overdose
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
SSRIs
- Side effects
GI symptoms- nausea, diarrhoea
Headache
Irritability
Anxiety
Reduced libido and sexual dysfunction
SNRI
- Type
- Examples
Selective noradrenaline re-uptake inhibitor
- Second generation antidepressant
Examples:
- Venlafaxine
- Duloxetine
Venlafaxine
- Type
- Side effects
SNRI
- Antidepressant
Side effects:
- Nausea
- Vertigo
- Headache
- Insomnia
Alpha-2 and 5-HT2c antagnoist
- Function
- Example
Second generation antidepressant
- Modulate the release of serotonin and NA release
Example
- Mirtazapine
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
Antipsychotics
Primarily increase action of dopamine
- D2/3 antagonists
- Also 5-HT action
Side effects:
- Extrapyramidal [haloperidol]
- Weight gain
- Glucose and lipid dysregulation
- Parkinsonism
Haloperiodol
- Action
- Side effects
D2/D3 antagonist
- Anti-psychotic
- Non-selective–> Extrapyramidal side effects
Aripiprazole
- Action
DA partial agonist
Atypical antipsychotic
- Treats bipolar
- Major depressive disorder
Lamotrigine
- Type
- Action
- Use
Anticonvulsant
- GABA agonist
- Inhibits Na+ channels
Use
- Prevents depressive relapse
- Not effective as an anti-manic agent
Carbamazepine in bipolar
Very effective in preventing manic relapse
- Not as effective in maintaining treatment
Treatment of acute manic episodes
DA antagonists
- Haloperidol
- Olanzapine
- Risperidone
- Quetiapine
Valproate [not in child bearing women]
Buspirone
- Side effect
5HT1A partial agonist
- Treats anxiety disorders
Interacts with grapefruit
Typical antipsychotic side effects [Haloperidol]
EPS
Tardive dyskinesia
