Thank you @
morinos. This is very interesting.
Could you please give a link to that doctor's post in that forum? So that from time to time I may have a look at what they discuss.
There is full post, which was translated with google translator special for you =)
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For colds will not necessarily decrease in depressive symptoms , and may be increased - it depends on the predominant type of immune response of the patient to infection : Th1 type response " aggressive" immune response , response -dependent T-cell type 1 , with early and excessive secretion of IFN, IL- 1 , IL- 2 , IL- 6, and such patients during infection gets worse and more often depressed "tail" after a cold , and "calm " answer - this early switch from Th1 to Th2 type cytokine secretion , when the " inflammatory " cytokines IFN, IL- 1 , IL- 2 , IL- 6 secretion quickly replaced inflammatory IL- 10 , IL- 12 and such patients during infections can become better because they have colds during the normalization of cytokine profile .
What is the impact tsiktokiny depression ? It is known that doses of interferon used to treat , for example, hepatitis C, or kidney cancer often does not cause depression , and very often, interleukins 1 and 2 - the same as in depressed patients , these interleukins and interferon can be chronically raised, and it is shown that changes in cytokine profile proportional not so much gravity as prolonging the depression.
As interferon penetrate the BBB ? And this does not occur , interferon causes inflammation of the vascular endothelium , endothelium releases prostaglandins and nitric oxide (NO), and those in turn , stimulate microglial cells - natural immune cells of the brain which serve as monocytes , macrophages , etc. Microglia in the BBB and begins to behave as well as on immune cells perferii , shifting the center of an immune response similar to that which occurs at the periphery , namely the same secrete IFN-a, IL- 1 , IL- 2 .
Neurons that are combined with this active microglia , " sick " : lose axons decreases their electrical activity occurring receptor changes reduced plasticity membranes neuron may just die - to undergo apoptosis , especially under the influence of FNO. And it was shown that patients with depression and aggression microglia activation and increased secretion of inflammatory cytokines occurs nowhere else but in the hippocampus and limbic where inflammation damages and kills neurons . Facts atrophy of the hippocampus and limbic transferred after many phases or one lingering long been known , as well as protective (and even restorative ) effect of antidepressants and mood stabilizers ETT process .
It is shown that the longer the depression, the more pronounced hypercortisolemic and shifts in cytokine profile and cellular immunity . Lowering the production of interferons and interleukins , while normalization of T cell function (a T- cell-mediated immunity is lowered by depression) during prolonged , protracted , polyvalent resistant depression helps "break" resistance , " connected" with the immune processes .
On the other hand the presence of the original patient autoimmune or atopic allergic diseases (asthma , psoriasis , atopic dermatitis, allergic rhinitis, allergic conjunctivitis) involves changes in cytokine profile and cellular immunity and depression in this patient requires intervention in immune mechanisms . The role of immune mechanisms can check laboratory - immunogram and cytokine profile , reduced function of T-suppressors and simultaneously lowered function of T-killers , can be increased humoral immunity, decreased phagocytic activity of leukocytes and macrophages , decreased T- suppressor activity predisposes to autoimmune processes , and reduced T- killer and macrophage explains frequent colds and stuff.
- immunogram - T-helpery/T-supressory ratio has a value of T- killer activity , NK- killer activity
- cytokine profile - Increased IFN-a, IL- 1 , IL- 2 , IL- 6 , FNO-a, a reduced inflammatory IL-10
- in the hormonal profile - elevated cortisol
( reduce the error in the study is possible, if carefully and measure 24 -hour urine cortisol or measure basal cortisol and cortisol after dexamethasone suppression , and a cannula into a vein before and set to take a stress-free , or saliva to measure cortisol )
Ie task is to reduce the activity of microglia. Actually BP also immunomodulators, through the influence of 5 -HT and other receptors on microglial cells , osuschestvlyut anti-inflammatory, cytoprotective effects , normalize cytokine secretion microglial cells . But sometimes this is not enough , when the immune regulation less mobile , need immunomodulators are able to penetrate the BBB , also reduce this most vicious microglia activation , alone they do not work , but only create opportunities for BP.
Today there are only two immunomodulator penetrating the BBB and affect cytokine and killer activity of microglia : levamisole and chloroquine ( hydroxychloroquine ) . Penetration through the BBB prerequisite normalization of cytokines on the periphery, in the blood does not give the desired effect , it is necessary to normalize the activity of microglia on the spot.
Levamisole , then 150 mg twice a week ( 150 mg for 2 consecutive days once a week - a more aggressive but toxic variant).
- Chloroquine is 250 mg . every evening after dinner.
Applies only one drug combination does not enhance the effect , but will toxic side effects . Immunomodulator therapy within 4-8 weeks , along with a powerful antidepressant in adequate doses (SNRI or TCA - because we are dealing with a lingering, resistant depression ) . Longer therapy only makes sense if there is concomitant disease which itself requires an immunomodulator (rheumatoid arthritis , SLE , etc.).
It is known that etanercept (soluble human type II receptors for FNO-a ( r75kD ) and human IgG1 to Fc- fragment , etanercept has dual action , inhibits tumor necrosis factor -alpha (FNO-a) and lymphotoxin ) enhances appetite and mood cancer patients when etanercept was applied for the treatment of ulcerative colitis , and so on . then noted that even before the clinical improvement in patients with normal sleep , appetite, behavior and mood. Etanercept experienced and depression - it helps potentiates BP - but it is a theoretical option - very expensive, it is important that once again shows the role of immune mechanisms .
Prolonged , resistant depression is a special stratagem neuronal interactions , immune and endocrine factors . You do not know what to answer (or not answer ) a particular patient - to add delagila or adding zheezy thyroid hormones , or, for example , ketoconazole . In any case in a given volume of the immune system and the hypothalamic - pituitary-adrenal axis is involved genesis of depression always . You can remember about BDNF, buyout increased against the background of ECT with antidepressants , lithium, and valproate . The ultimate goal is the same - rescue neurons from apoptosis .
What happens after the injection pyrogenal or after administration of a decent dose of interferon or IL- 1, 22 ? Condition very similar to depression in many ways , the so-called sickness behavior: lack of appetite , sleep disturbances , while drowsiness, weakness, lethargy , weakness , fatigue, aches and pain in muscles, joints, bones . It is believed that interferon, interleukins , FNO-a partly responsible for the lack of appetite , weight loss , fatigue , weakness , drowsiness , lethargy in depressed patients . Selective antagonists of IL- 1, 2, also showed interesting effects on affect.
With the increase in IL- 1, 2 , FNO-a - automatically increased cortisol - the adrenal glands are trying to counter inflammation , on the other hand, if the affected neurons of the hypothalamus , the adverse effect on the adrenal glands excited only amplified, and the relationship of cortisol and depression - obvious .
And this applies not only to depression. In schizophrenia also exhibit elevated levels of inflammatory cytokines in the blood and the activity of microglia , and precisely in the frontal lobes - where reduced activity or neuronal death cries deficit symptoms .
Atypical antipsychotics act including immunoregulatory way through the 5 -HT2, implementing prevention of neuronal loss in the prefrontal cortex ."
