Inflammation and Depression- Hunter Flashcards
Smith suggested that depression was caused by inflammation and acute phase response via cytokines such as (blank, blank, and blank)
TNF-alpha, IL-1Beta. and IL-6
Smith also suggested that cytokines gained access to the brain and caused hyperactivity of the (blank), disturbance of (blank) and cause neurovegative symptoms
HPA axis
serotonin metablism
What are neurobegative symptoms?
sleep disturbances, decreased appetite and energy
App. 1/3rd of people with depression have higher levels of the inflammatory marker (blank)
CRP
App. 1/3rd of people with depression have higher levels of the proinflammatory cytokines (blank X 3)
TNF-alpha
IL-1B
IL-6
Are the levels of proinflammatoy cytokines and inflammatory maker similiar to levels seen in autoimmune or infectious disease?
no
What are the levels of proinflammatoy cytokines and inflammatory markers similiar to?
diseases where inflammation in implicated (i.e CV disease, stroke, diabetes)
THe most replicated findings pertain to raised (blank) and (blank). These cytokines may serve as biomarkers for risk or prognostic indicators.
CRP
IL-1B
The most replicated findings pertain to raised CRP and IL-1b confirmed by at least two recent meta-analyses. These cytokines may serve as (blank) for risk or (blank)
biomarkers
prognostic indicators
T or F
Not all patient with depession have elevated inflammatory mediators
T
Why is it difficult to justify depression as an inflammatory illness?
because it is neither necessary nor sufficient to be the sole cause of depression
The data supports that inflammation as a feture of depression does exist in a subset of patients and this is due to (Blank) and (Blank) factors for depression
environmental
genetic
Is inflammation/immune disruption specific to depression?
nope, found in lots of neuropsychiatric conditions including schizophrenia
T or F
depression occurs at a 5-10 times higher rate in those with known inflammatory diseases
T
What are the peripheral inflammatory diseases that cause depression?
-psoriasis
-rheumatoid arthritis
-IBS
(average rate of depression is 15%)
Depression is also common in diseases of the central nervous system such as (blank)
Multiple sclerosis
50% are sad, suicide rate as high a 15%
How do you treat hep c, why is this bad?
IFN-alpha and IL-2
->causes a cytokine storm that can resut in depression
(blank) percent of patients treated with IFN-alpha develop clinical depression
30
T or F
anti-inflammatory treatments have been associated with antidepressant effects
T
What was the “proof” that anti-inflammatories cure depression?
gave anti-TNF alpha antibody (infliximab) to Chrohn’s disease patients and it resulted in remission in depression
A study found the (Blank) percent of patients with psoriasis and depression who were treated with (Blank) showed improved becks depression inventory scores , with an effect size comparable to antidepressants. What was awesome about this study?
50%
Etanercept (soluble TNF-alpha receptor)
These reults were found to be independent of improvement in psoriasis
A study showed that (blank) added to reboxetine (a selective norepinephrine reuptake inhibitor) improved depressive symptoms more than reboxetine alone.
celecoxib
I.e add an anti-inflammatory to an anti-depressant will reduce depression more than an anti-depressant alone
What does celecoxib do?
Cox 2 inhibitor
What were antidepressant shown to reduce levels of (especially SSRI)?
IL-1B, IL-6 along with depressive symptoms
note: did not reduce levels of TNF-alpha**
Antidepressants block the effect of (blank) in the brain
inflammatory cytokines
The data suggests that inflammation is associated with depression, however this inflammation induced depression may only occur in a subset of (Blank) susceptible individuals
genetically
Inflammation may not only act as a (blank) factor that pushes a person into depression, but also as a (blank) factor that may pose an obstacle to recovery
precipitating factor
perpetuating factor
Inflammatory mediators may be potential (blank), aiding in diagnosis or even helping to predict prognosis
biomarkers
Treatment with (blank) has promise in some patients with depression
anti-inflammatory drugs
Can you find cytokines in the brain?
yes! they are made their and the brain couldnt survive without them
Cytokines in the brain are produced by what ?
neurons, microglia, and astrocytes
Neurons, microglia and astrocytes have (blank) receptors
cytokine
Do peripheral cytokine have an effect on the brain?
yes through 4 different mechanisms
What are the four ways that peripheral cytokines can effect the brain?
- triggering afferents
- humoral pathway (volume diffusion)
- humoral pathway 2 (cytokine transporter)
- secretion of secondary messangers
Cytokines produced in the periphery trigger sensory afferents of cranial nerves that transmit signals to the brain. This is called the (blank) pathway. What nerves transmit the signal?
(vagal, glossopharyngea nerves)
Neural pathway
How do peripheral cytokines get to the brain via the humoral pathway?
1) volume diffusion of cytokines from “leaky” circumventricular organs, which lie outside the blood-brain barrier (BBB)
2) saturable cytokine transporters in the BBB
How do secondary messangers allow for peripheral cytokines to access the brain?
secondary messangers like (PGE2 and NO) are secreted by cells that make up the BBB in response to peripheral cytokines
Proinflammatory cytokines can influence the (blank X 3) of autoimmune neurotransmitters like serotonin and dopamine
metabolism, production and reuptake
Proinflammatory cytokines can have an effect on neuroplasticity by messing with (blank)
BDNF
Proinflammatory cytokines can affect (Blank) which will influence the production of cortisol thus lessening the inflammatory response and reducing depression. What happens if you dont have this normal response?
CRH levels
you will get glucorticoid resistance and lose your feedback mechanism so reduce inflammation and thus will get depression
Stress can cause stimulation of the (blank) system which will trigger the release of the neurotransmitter (blank)
sympathetic nervous system
NE
Macrophages have what kind of receptors and why is this important?
adrenergic and ACh reeptors
Cuz when the sympathetic nervous system is triggered by stress, norepinephrine will be released and bind to macrophages.
When a macrophage gets bound by NE what happens?
What does this indicate about stress?
upregulation of NFkB which increaes proinflammatory cytokines
psychosocial stress can cause depression
What can the motor vagus do in regards to inflammation?
normally: can downregulate it via ACh
In profound stress: motor vagus system falas apart and wont have negative feedback
What is the theory behind glucocorticoid resistance?
the inability for your glucocorticoids to inhibit NFkB and thus you get lots of inflammation and then depression
Infection or tissue damage recognized by pattern recognition receptors such as (Blank) stimulates (blank).
TLR-4
NF-kB
Proinflammatory mediators are produced and secreted …what are they?
cytokines TNF-alpha, IL-1B, IL-6
Cytokines participate in various pathways related to depression. Cytokines can alter (blank) and (Blank) signaling
serotonergic and dopaminergic
Cytokines participate in various pathways related to depression. Cytokines can activate (Blank) and engage the HPA axis (cortisol production)
CRH
Cytokines participate in various pathways related to depression. Cytokines can disrupt (blank)
synaptic plasticity (BDNF)
What do environmental stress do that make you depressed?
activate sympathetic neurons that synapse on macrophages via NE and stimulates NF-kB (proinflammatory)
Stressors also induce withdrawal of (Blank) input
inhibitory motor vagal. I.e wont inhibit NFKB so you have increase in NFkB and increase in proinflammatory cytokines
Activation of the mitogen activated protein kinase pathway (MAP- kinase pathway) inhibits the function of (blank), thereby releasing Nf-kB from negative regulation by glucocorticoids (glucocorticoid resistance)
glucocorticoid receptors
