The role of Neuroimflammation in affective disorder Flashcards
What is the role of inflammation?
Heal, defend and repair
What are the key processes of the inflammatory response?
Blood platelets stop the bleeding
mast cells increase blood flow to the area
Increased blood brings Neutrophils-Phagacytosis
Macrophages release cytokines to blood vessels to increase immune response
What are the two elements that regulate inflammation?
HPA axis-controls stress response
GC receptors- Negative feedback loop- Immunosuppressive and anti-inflammatory response
What are the names given to the activation and negative alteration of GR?
Transactivation and Transrepression
What are the disorders found will Hyper and Hypo HPA activation?
Hyper: MDD, Schizophrenia, Alzhiemers
Hypo: PTSD, Chronic Fatigue, Atypical Depression
What is the relationship between MDD and HPA axis activity?
Up-regulation is consistently linked with MDD
As is :
Enlarged adrenals
Increased cortisol
Exageratted response to ACTH
What is the paradox regarding cortisol, depression and inflammation?
Depressed patients show increased cortisol and inflammation despite cortisol being an anti-inflammatory.
Occurs due to Glucocorticoid resistance.
What is GC resistance?
The inability of the GC hormone to regulate it’s own production, leading to an inability to inhibit CRH and ACTH production.
How does impaired GC receptor sensitivity increase inflamtion and what are the consequences?
The usual response to stop producing inflammatory cytokines is not stopped.
Leading to:
Higher levels of cytokines, higher CRP
Inflammation Genes
All seen in depressed patients.
What is the effect of depression on the heart?
Increased CRP due to inflammation increases:
Heart Attacks
Angina
Cardiac events
This risk factor is bi Directional.
What are the highest 2 burdens of disease?
Leading causes of disability in Developed countries:
1: Heart Disease
2: Depression
Estimated entire world 2020
How has the blood brain barrier protection hypothesis been challenged recently?
Cytokines have been observed to breakdown BBB
Cytokines have also been seen to use transport molecules.
Passive penetration too
How can inflammation effect depression via serotonin production?
Inflammation and the pro inflammatory cytokines disrupt the tryptophan production increasing IDO and KMO leading to 3 HydroxyKryunene and Quinollinic Acid leading to the neurotic effect of NMDA agonists.
Why may 1/3 of conventional therapies fail?
They fail to address the inflammation and immune response.
