L6 Affective Disorders Neurobiology and Treatment Flashcards
Biological basis of depression
Disruption in the 5HT and NA system
Disruption of HPA
Inflammation
What is HPA-axis function?
Hypothalamic pituitary adrenal (HPA) axis is our central stress response system.
intertwining of the central nervous system and endocrine system.
Stress triggers release of hormones
- Hypothalamus releases CRH (Corticotrophin releasing hormone)
- stimulated release of ACTH (adrenocorticotrophin) from the anterior pituitary - ACTH stimulated glucocorticoid release from adrenal glands- this stimulates cortisol release
Causes of depression
Multifactorial
Incompletely understood
Interactions of genetic factors
Stress
How does depression affect 5HT/NA systems? [2]
1) 5-HT concentrations
(acute tryptohan depletion) studies
2) Reduced 5-HT Transporter in post- mortem suicide studies
Where is serotonin synthesised?
Raphe-Nucleus
Amitriptyline
- Class
- MOA
- Trycyclic antidepressents
- first generation
-Nonselectively inhibit reuptake of monoamines (5HT, NE, DA)
Fluoxetine
-second generation antidepressent
- second generation antidepressent
- SSRI: Selective serotonin reuptake inhibitors
SSRIs
large spectrum of action
Efficacy equal to tryciclics in outpatients
Large spectrum of action (OCD, PTSD, Panic, GAD, social anxiety)
Low toxicity and safe in overdose
Treatment of bipolar and mania
Lithium
- Narrow therapeutic index
- Mood stabilising
- Anti-suicidal
- Effects on kidneys ans thyroid
Antiepileptics
Valproate
Lamotrigine
Carbamazepine
How can a depressive episode be treated?
Antipsychotics (Quetiapine, lurasidone)
SSRI- Fluoxetine/Olanzapine combinations
Antidepressants to be co-prescribed with an anti-manic drug
Consider Lamotrigine (usually with antimanic drug)
How can acute manic episodes be treated?
Dopamine antagonists (haloperidol, olanzapine, risperidone and quetiapine)
Valproate
Discontinue any antidepressant treatment
HPA dysfunction in depression
stress = lots of cortisol via HPA axis
cortisol inhibits activity in hypothalamus and hippocampus
Glucocorticoid Receptor alterations- affects sensitivity to cortisol
[Lack of dexamethasone suppression]
Inflammation and Depression
Increase in inflammatory markers= stimulate depressive episodes
Raised plasma cytokine levels (provokes depression)
- IL-6
- TNF-α
MAOi
- Class
- MOA
First generation antidepressant.
Nonselectively inhibit enzymes involved in breakdown of monoamines (5HT, DA, NE)
Non-selective so affects wide range of symptoms…
