health discussion has abundant information about depression.Depression and Candida

Poor intestinal flora can contribute to depression by altering the immune system. Let’s examine this relationship a bit closer. Cytokines are produced by our immune system. In depression, there is an increase in inflammatory cytokines called IL-1, IL-6, and TNF. These same cytokines can be increased by exposure to the LPS in the cell wall of gram-negative intestinal bacteria. By increasing these cytokines, intestinal bacteria have been shown to induce depression, anxiety and cognition impairment.

Antidepressants modify the brain’s response to cytokines. In fact, this might be one of the ways that these drugs work to relieve depression. The same inflammatory cytokines that are associated with depression can activate the hypothalmic-pituitary-axis (HPA). An activated HPA is also associated with depression. These same inflammatory cytokines can also cause central hypothyroidism. There is some indication that central hypothyroidism is present in depression. However, this type of central hypothyroidism is not easily found by the usual tests. If central hypothyroidism exists, it is important to treat it. Without treatment, there is less chance that anti-depressants will work.

Central hypothyroidism means that there is not enough thyroid hormones circulating in the body because the brain is not regulating them properly. Doctors often employ a TSH test to screen for thyroid problems. TSH is a chemical produced in the brain that tells your thyroid gland to produce thyroid hormones. If TSH is high, it usually means that your thyroid is having trouble meeting the demands of the body and that you need a supplement of thyroid hormones. However, TSH is suppressed in central hypothyroidism. The brain isn’t making enough of it in response to the body’s need for thyroid. Therefore TSH won’t register high even though the body needs more thyroid hormone.

Unfortunately, many institutions rely solely on this TSH test to screen patients for thyroid abnormalities. The TSH test will not detect central hypothyroidism. To detect central hypothyroidism, a TRH test is usually employed. However, a doctor cannot even rely on the TRH test. In depression, the suppression of TSH seems to occur at night, not during the day when a TRH test is usually administered. Therefore many cases of hypothyroidism in depression can be missed.

A doctor cannot even totally rely on the thyroid hormone levels in the blood to tell him if hypothyroidism is present. There is a slow clearance of thyroid hormones from the blood when hypothyroidism exists. This throws off these tests.

A form of thyroid hormone called T3 seems to be very important in the treatment of depression. Be careful to find a doctor willing to gradually try introducing the T3 form of thyroid into your treatment protocol. Unfortunately, most doctors have been taught to just use T4 thyroid when treating hypothyroidism. An alternative doctor or a psychiatrist is more likely to employ T3 thyroid. (Natural thyroids like Armour contain T4 and T3 thyroid.)

There is another relationship between your immune system, the gut and depression. A healthy intestine will produce an enzyme called DPP IV. (The intestines and kidney are where most of this enzyme is created. Certain intestinal bacteria can create this enzyme too.) This enzyme is important for the digestion of food, and it is important for the immune system. It appears to have a major role in depression, as evidenced by the following observations.

1.    The activity of this enzyme is low in the blood serum of people with depression.

2.    Treatment with either interferon-alpha or IL-2 will reduce DPP IV activity in the blood. This reduction in DPP IV activity directly correlates with an increase in depressive symptoms.

3.    The DPP IV enzyme is important for methylation in the body. Methylation appears to be important in the treatment of depression. (eg. SAMe)

4.    The DPP IV enzyme degrades (helps to get rid of) IL-1, IL-6, and TNF. These inflammatory cytokines are often elevated in depression.

DPP IV is contained in several digestive aids on the market. However, as of yet, there are no studies where DPP IV has been used to treat depression. Used by itself, DPP IV may or may not be a good idea in the treatment of depression. The ideal solution is to heal the gut and let the body create its own DPP IV and other digestive peptidases.

References

1.    Maes M. “Evidence for an immune response in major depression: a review and hypothesis.” Prog Neuropsychopharmacol Biol Psychiatry. 1995 Jan;19(1):11-38. Review, and

2.    Reichenberg A, Yirmiya R, Schuld A, et al: Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 2001, 58:445-452. (Low dose Salmonella toxin induced anxiety, depression, and cognition impairment. Psychological changes were correlated with the increase in IL-1, IL-6, and TNF.).

3.    Maes M, et al.. “Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: relationships with immune-inflammatory markers.” Psychoneuroendocrinology. 1997 Feb;22(2):65-78

4.    Maes M, Capuron L, Ravaud A, Gualde N, Bosmans E, Egyed B, Dantzer R, Neveu PJ. “Lowered serum dipeptidyl peptidase IV activity is associated with depressive symptoms and cytokine production in cancer patients receiving interleukin-2-based immunotherapy.” Neuropsychopharmacology 2001 Feb;24(2):130-40

5.    Maes M, Bonaccorso S, Marino V, Puzella A, Pasquini M, Biondi M, Artini M, Almerighi C, Meltzer H “Treatment with interferon-alpha (IFNalpha) of hepatitis C patients induces lower serum dipeptidyl peptidase IV activity, which is related to IFNalpha-induced depressive and anxiety symptoms and immune activation.” Mol Psychiatry 2001 Jul;6(4):475-80

6.    Wang J, Dunn AJ. “The role of interleukin-6 in the activation of the hypothalamo-pituitary-adrenocortical axis and brain indoleamines by endotoxin and interleukin-1 beta.”

7.    Lopez JF, Vazquez DM, Chalmers DT, Watson SJ “Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide”, Ann N Y Acad Sci 1997 Dec 29; 836:106-34 (Increase activity of the HPA axis is associated with suicide.)

8.    Bartalena L, Placidi GF, Martino E, Falcone M, Pellegrini L, Dell'Osso L, Pacchiarotti A, Pinchera A. “Nocturnal serum thyrotropin (TSH) surge and the TSH response to TSH-releasing hormone: dissociated behavior in untreated depressives.” J Clin Endocrinol Metab 1990 Sep;71(3):650-5 (a lack of nocturnal TSH surge supports the case for some degree of central hypothyroidism in depression.)

9.    Cooke RG, Joffe RT, Levitt AJ., “T3 augmentation of antidepressant treatment in T4-replaced thyroid patients.” J Clin Psychiatry, 1992 Jan;53(1):16-8,

10.    Bunevicius R, Prange AJ “Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism.” Int J Neuropsychopharmacol 2000 Jun;3(2):167-174

11.    Joffe RT, Singer W, “Antidepressants and thyroid hormone levels.” Acta Med Austriaca. 1992;19 Suppl 1:96-7.,

12.    Sokolov ST, Levitt AJ, Joffe RT. “Thyroid hormone levels before unsuccessful antidepressant therapy are associated with later response to T3 augmentation.” Psychiatry Res. 1997 Mar 24;69(2-3):203-6

13.    Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M., “Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis.” Eur Neuropsychopharmacol 2001 Jun;11(3):203-8

14.    Hildebrandt M, Reutter W, Arck P, Rose M, Klapp B, “A guardian angel: the involvement of dipeptidyl peptidase IV in psychoneuroendocrine function, nutrition and immune defence. Clinical Science 2000, 99, 93-104

15.    Sasaki M, et al, “Comparison of proteolytic activities in various lactobacilli” J Dairy Res 1995 Nov; 62(4):601-10