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Depression is a broad term for a host of unpleasant feelings, including emotional numbness, lack of energy and motivation, feeling like a failure and feeling undesirable. These feelings frequently show up for the first time in middle-aged people who feel like they're over the hill. Elderly people too frequently get depressed, and are particularly at risk of suicide. Depression is a growing problem among teenagers as well. Doctors have long known that giving estrogen to women and testosterone to men during mid-life can avert symptoms of depression, although the effects have never been phenomenal. Reports are stacking up that another hormone, dehydroepiandrosterone (DHEA), works better-much better. DHEA turns into both estrogen and testosterone. And it just so happens that it goes south about the time people start thinking about being "over the hill." DHEA is involved in brain chemistry. It's not only utilized by the brain, it's manufactured by it. Although researchers don't know what it's supposed to do yet, they do know that giving a person 500 mg of DHEA will cause them to have more REM (dream) sleep. This suggests that DHEA has a major role in the brain. DHEA is the only hormone besides cortisol that has consistently been linked with depression. It was studied as far back as the 1950s as an antidepressant. Back then, researchers reported that it gave people energy and confidence, and made them less depressed. While it seemed to work great, no one followed up on the original studies. DHEA emerged on the scene again in the 1980s when interest in antiaging hormones geared up. It was noted then that antidepressant activity was part of DHEA's overall antiaging benefits. Then, in 1996, a report suggested that DHEA's antidepressant effects might be direct, and not just part of its overall antiaging effect. Researchers at Cambridge University then discovered that young kids with major depression have abnormally low levels of DHEA (and abnormally high levels of cortisol). This seemed to confirm that DHEA had a direct effect on mood. In the late 1990s, DHEA's mood-enhancing effect was confirmed in a study from the University of California at San Diego. Researchers analyzed old data from a large study that had been done on 699 older women living in Rancho Bernardo, California. Their analysis is the largest study ever done on the association between levels of DHEA and depression. Nine different hormones had been measured during the study, which took place during the 1970s and '80s. Included in the measurements were such things as bioavailable testosterone and sex hormone binding globulin. When the results were in, DHEAS (DHEA sulfate, a metabolite) was the only hormone strongly associated with depression. Women with the least DHEA were more likely to be depressed. This confirms an earlier study in which the percentage of women with depression was 21.7% if they had no detectable DHEA, versus 4.6% if DHEA could be detected in their blood. Interestingly, levels of DHEA in the Rancho study correlate with mood even within the normal range. In other words, the lower the DHEA, the worse the mood got. And DHEA correlated with mood irrespective of whether a person was taking antidepressants or not. DHEA Stops Depression A group at UC at San Francisco went at the DHEA/depression question another way. Researchers decided to give DHEA to people with depression and see if it would help. In the first double-blind, placebo-controlled study on DHEA's potential as an antidepressant, 11 patients with major depression were given up to 90 mg/day of DHEA for six weeks, and 11 were given a placebo. One week before the study actually began, all patients were given a placebo to weed out people who would respond to a sugar pill. People getting the real McCoy received 30 mg/day of DHEA for the first two weeks, 60 the second two weeks, and 90 the last two weeks. The idea of the graduated dose was to bring patients up to the DHEA levels they had when they were 20-30 years old (DHEA declines with age). Although the amount of DHEA wasn't adjusted individually, as it could have been, the graduated dose approximates what it takes to reach a "youthful" level in most people, according to Dr. Owen Wolkowitz, principle investigator on the study. Some of the participants were taking antidepressants. For these people, the antidepressants were either working partially, or not working at all. Only people who had been on the same antidepressant for at least six weeks without changing were allowed in the study, and no changes could be made in anyone's medication during the study. After six weeks, psychological tests indicated that about half the participants responded to DHEA therapy, with an overall enhance of mood scores by 30.5%. This is close to the response rate of antidepressant drugs. An even better response was seen in another study conducted by researchers at the National Institute of Mental Health. In this study, participants were middle-aged people with dysthymia, a chronic, low-grade depression. They were given 90 mg of DHEA a day for three weeks, then 450 mg a day for three weeks more. A battery of psychological tests were administered, including the Hamilton Depression Rating Scale, the Beck Depression Inventory, a visual analogue scale, and the Cornell Dysthymia Scale. (In addition, a day's worth of cognitive function tests were given, but DHEA didn't show a significant effect on cognition in this study. However, the researchers note a trend towards better cognition that could have played out if the study had lasted longer). None of the patients were taking any prescription drugs whatsoever except one man who was taking a hypertension drug. The study was set up in a very rigorous way: all participants got the drug or the placebo for six weeks, and then they were all secretly switched. All people involved in the study were blind to who was getting what. DHEA significantly alleviated the participants' depression. Seven symptoms in particular got much better: lack of pleasure, low energy, low motivation, emotional numbness, sadness, inability to cope and excessive worry. DHEA worked for most people within 10 days. If the supplement was stopped, the symptoms came back. Overall, the response rate was 60%, which is better than what antidepressants usually do for dysthymia. Ninety milligrams a day was sufficient. No extra benefit was provided by the 450 mg dose. Researchers have different theories about how DHEA alleviates depression. Both DHEA and DHEAS can cross the blood-brain barrier and interact with the brain directly. DHEA can affect serotonin, GABA receptors and other brain factors. A recent study indicates it might modulate the serotonin signaling pathway. DHEA also has anti-stress effects that may be part of its antidepressant action. Research shows that cortisol, the stress hormone, is elevated in major depression. DHEA counteracts cortisol. Interestingly, calmness appears to be associated with higher levels of DHEA. People who practice transcendental meditation have higher levels of DHEA than those who don't. People who took part in a stress reduction program were able to increase their DHEA by 100%. At the same time, they reduced their stress hormone by 23%. Exercise has been reported to enhance mood. This mood-enhancing effect may be due to DHEA. Exercise raises levels of DHEA. In turn, DHEA has positive effects on the heart. In a study published in the American Journal of Cardiology, depression and heart attack went together: women with depression were at greater risk of heart attack, and vice-versa. One way DHEA is good for the heart is that it keeps arteries clear. In a study from Italy, higher levels of DHEAS correlated with less carotid artery thickening, and a lower risk of heart attack and stroke. DHEA works by inhibiting the growth of cells in the arteries. Alleviating depression is the latest in a long list of benefits from DHEA. Antioxidant protection of the brain, bone enhancement, and heart protection are a few of the other benefits scientists are uncovering about the body's most abundant steroid. Considering the side effects and lag time of anti-depressants, DHEA is a good alternative. ---------------------------------------------------- References Barrett-Connor E, et al. 1999. Endogenous levels of dehydroepiandrosterone sulfate, but not other sex hormones, are associated with depressed mood in older women: the Rancho Bernardo Study. J Am Geriatr Soc 47:685-91. Bernini GP, et al. 1999. Endogenous androgens and carotid intimal-medial thickness in women. J Clin Endocrinol Metab 84:2008-12. Bloch M, et al. 1999. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry 45:1533-41. Furutama D, et al. 1998. Inhibition of migration and proliferation of vascular smooth muscle cells by dehydroepiandrosterone sulfate. Biochim Biophys Acta 1406:107-14. Glaser JL, et al. 1992. Elevated serum dehydroepiandrosterone sulfate levels in practitioners of the Transcendental Meditation (TM) and TM-Sidhi programs. J Behav Med 15:327-41. Goodyer IM, et al. 1996. Adrenal secretion during major depression in 8-to16-year olds. Altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation. Psychol Med 26:245-56. Inagaki M, et al. 1999. Effect of acute and chronic administration of dehydeoepiandrosterone on (+/-)-1-(2,5-dimethosy-4-iodophenyl)-2-aminopropane-induced wet dog shaing behavior in rats. J Neural Transm 106:23-33. Johnson LG, et al. 1997. Effects of estrogen replacement therapy on dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol responses to exercise in postmenopausal women [published erratum appears in Fertil Steril 1998 Mar;69:606]. Fertil Steril 68:836-43. Lavie CJ, et al. 1999. Effects of cardiac rehabilitation and exercise training programs in women with depression. Am J Cardiol 83:1480-3, A7. McCraty R, et al. 1998. The impact of a new emotional self-management program on stress, emotions, heart rate variability, DHEA and cortisol. Integr Physiol Behav Sci 33:151-70. Morales AJ, et al. 1995. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 78:1360-67; correction, 80:2799. Sands DE, et al. 1952. Treatment of inadequate personality in juveniles by dehydroisoandrosterone: preliminary report. BMJ 2:66-68. Strauss EB, et al. 1955. Use of dehydroepiandrosterone in psychiatric practice. J Neurol Neurosurg Psychiatry 18:137-44. Wolkowitz OM, et al. 1995. Antidepressant and cognition-enhancing effects of DHEA in major depression. Ann NY Acad Sci 477:337-39. Wolkowitz OM, et al. 1999. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 156:646-49. Yaffe K, et al. 1998. Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry 1:694
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