Inflammation and Depression- Hunter

Question 1

Smith suggested that depression was caused by inflammation and acute phase response via cytokines such as (blank, blank, and blank)

Answer 1

TNF-alpha, IL-1Beta. and IL-6

Question 2

Smith also suggested that cytokines gained access to the brain and caused hyperactivity of the (blank), disturbance of (blank) and cause neurovegative symptoms

Answer 2

HPA axis

serotonin metablism

Question 3

What are neurobegative symptoms?

Answer 3

sleep disturbances, decreased appetite and energy

Question 4

App. 1/3rd of people with depression have higher levels of the inflammatory marker (blank)

Answer 4

CRP

Question 5

App. 1/3rd of people with depression have higher levels of the proinflammatory cytokines (blank X 3)

Answer 5

TNF-alpha
IL-1B
IL-6

Question 6

Are the levels of proinflammatoy cytokines and inflammatory maker similiar to levels seen in autoimmune or infectious disease?

Answer 6

no

Question 7

What are the levels of proinflammatoy cytokines and inflammatory markers similiar to?

Answer 7

diseases where inflammation in implicated (i.e CV disease, stroke, diabetes)

Question 8

THe most replicated findings pertain to raised (blank) and (blank). These cytokines may serve as biomarkers for risk or prognostic indicators.

Answer 8

CRP

IL-1B

Question 9

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)

Answer 9

biomarkers

prognostic indicators

Question 10

T or F

Not all patient with depession have elevated inflammatory mediators

Answer 10

T

Question 11

Why is it difficult to justify depression as an inflammatory illness?

Answer 11

because it is neither necessary nor sufficient to be the sole cause of depression

Question 12

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

Answer 12

environmental

genetic

Question 13

Is inflammation/immune disruption specific to depression?

Answer 13

nope, found in lots of neuropsychiatric conditions including schizophrenia

Question 14

T or F

depression occurs at a 5-10 times higher rate in those with known inflammatory diseases

Answer 14

T

Question 15

What are the peripheral inflammatory diseases that cause depression?

Answer 15

-psoriasis
-rheumatoid arthritis
-IBS
(average rate of depression is 15%)

Question 16

Depression is also common in diseases of the central nervous system such as (blank)

Answer 16

Multiple sclerosis

50% are sad, suicide rate as high a 15%

Question 17

How do you treat hep c, why is this bad?

Answer 17

IFN-alpha and IL-2

->causes a cytokine storm that can resut in depression

Question 18

(blank) percent of patients treated with IFN-alpha develop clinical depression

Answer 18

30

Question 19

T or F

anti-inflammatory treatments have been associated with antidepressant effects

Answer 19

T

Question 20

What was the “proof” that anti-inflammatories cure depression?

Answer 20

gave anti-TNF alpha antibody (infliximab) to Chrohn’s disease patients and it resulted in remission in depression

Question 21

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?

Answer 21

50%

Etanercept (soluble TNF-alpha receptor)

These reults were found to be independent of improvement in psoriasis

Question 22

A study showed that (blank) added to reboxetine (a selective norepinephrine reuptake inhibitor) improved depressive symptoms more than reboxetine alone.

Answer 22

celecoxib

I.e add an anti-inflammatory to an anti-depressant will reduce depression more than an anti-depressant alone

Question 23

What does celecoxib do?

Answer 23

Cox 2 inhibitor

Question 24

What were antidepressant shown to reduce levels of (especially SSRI)?

Answer 24

IL-1B, IL-6 along with depressive symptoms

note: did not reduce levels of TNF-alpha**

Question 25

Antidepressants block the effect of (blank) in the brain

Answer 25

inflammatory cytokines

Question 26

The data suggests that inflammation is associated with depression, however this inflammation induced depression may only occur in a subset of (Blank) susceptible individuals

Answer 26

genetically

Question 27

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

Answer 27

precipitating factor | perpetuating factor

Question 28

Inflammatory mediators may be potential (blank), aiding in diagnosis or even helping to predict prognosis

Answer 28

biomarkers

Question 29

Treatment with (blank) has promise in some patients with depression

Answer 29

anti-inflammatory drugs

Question 30

Can you find cytokines in the brain?

Answer 30

yes! they are made their and the brain couldnt survive without them

Question 31

Cytokines in the brain are produced by what ?

Answer 31

neurons, microglia, and astrocytes

Question 32

Neurons, microglia and astrocytes have (blank) receptors

Answer 32

cytokine

Question 33

Do peripheral cytokine have an effect on the brain?

Answer 33

yes through 4 different mechanisms

Question 34

What are the four ways that peripheral cytokines can effect the brain?

Answer 34

- triggering afferents - humoral pathway (volume diffusion) - humoral pathway 2 (cytokine transporter) - secretion of secondary messangers

Question 35

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?

Answer 35

(vagal, glossopharyngea nerves) | Neural pathway

Question 36

How do peripheral cytokines get to the brain via the humoral pathway?

Answer 36

1) volume diffusion of cytokines from "leaky" circumventricular organs, which lie outside the blood-brain barrier (BBB) 2) saturable cytokine transporters in the BBB

Question 37

How do secondary messangers allow for peripheral cytokines to access the brain?

Answer 37

secondary messangers like (PGE2 and NO) are secreted by cells that make up the BBB in response to peripheral cytokines

Question 38

Proinflammatory cytokines can influence the (blank X 3) of autoimmune neurotransmitters like serotonin and dopamine

Answer 38

metabolism, production and reuptake

Question 39

Proinflammatory cytokines can have an effect on neuroplasticity by messing with (blank)

Answer 39

BDNF

Question 40

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?

Answer 40

CRH levels you will get glucorticoid resistance and lose your feedback mechanism so reduce inflammation and thus will get depression

Question 41

Stress can cause stimulation of the (blank) system which will trigger the release of the neurotransmitter (blank)

Answer 41

sympathetic nervous system | NE

Question 42

Macrophages have what kind of receptors and why is this important?

Answer 42

adrenergic and ACh reeptors | Cuz when the sympathetic nervous system is triggered by stress, norepinephrine will be released and bind to macrophages.

Question 43

When a macrophage gets bound by NE what happens? | What does this indicate about stress?

Answer 43

upregulation of NFkB which increaes proinflammatory cytokines psychosocial stress can cause depression

Question 44

What can the motor vagus do in regards to inflammation?

Answer 44

normally: can downregulate it via ACh | In profound stress: motor vagus system falas apart and wont have negative feedback

Question 45

What is the theory behind glucocorticoid resistance?

Answer 45

the inability for your glucocorticoids to inhibit NFkB and thus you get lots of inflammation and then depression

Question 46

Infection or tissue damage recognized by pattern recognition receptors such as (Blank) stimulates (blank).

Answer 46

TLR-4 | NF-kB

Question 47

Proinflammatory mediators are produced and secreted ...what are they?

Answer 47

cytokines TNF-alpha, IL-1B, IL-6

Question 48

Cytokines participate in various pathways related to depression. Cytokines can alter (blank) and (Blank) signaling

Answer 48

serotonergic and dopaminergic

Question 49

Cytokines participate in various pathways related to depression. Cytokines can activate (Blank) and engage the HPA axis (cortisol production)

Answer 49

CRH

Question 50

Cytokines participate in various pathways related to depression. Cytokines can disrupt (blank)

Answer 50

synaptic plasticity (BDNF)

Question 51

What do environmental stress do that make you depressed?

Answer 51

activate sympathetic neurons that synapse on macrophages via NE and stimulates NF-kB (proinflammatory)

Question 52

Stressors also induce withdrawal of (Blank) input

Answer 52

inhibitory motor vagal. I.e wont inhibit NFKB so you have increase in NFkB and increase in proinflammatory cytokines

Question 53

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)

Answer 53

glucocorticoid receptors