Depression and DHEA Treatment

Depression and DHEA Treatment

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.
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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.

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Great read!!!!!!!!!!! Thanks… I just starting taking DHEA about two weeks ago and I’m already feeling better. :)

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

A Hypothetical Explanation of Panic Disorder



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Copyright ã 2001 James Michael Howard and German Journal of Psychiatry 2001; 4: 40-42


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Abstract



Panic attacks may result from severe reduction of dehydroepiandrosterone (DHEA) in a person of low DHEA with normal or increased levels of cortisol. That is, an excessive ratio of cortisol to DHEA occurs which extinguishes the effects of unstable DHEA and magnifies the effects of cortisol. Prolactin increases during panic attacks and is correlated with attack severity. That is, prolactin increases to stimulate DHEA, but the response is inadequate to stabilize the DHEA to cortisol ratio and inhibit prolactin production. Therefore, prolactin remains elevated during an attack. Panic attacks occur when the effects of excessive cortisol excite prolactin stimulation of DHEA in a person who cannot respond with adequate DHEA.

Key words: cortisol, cholecystokinin, dehydroepiandrosterone, panic disorder, prolactin

The physiological mechanism of panic attacks is unexplained. I suggest panic attacks occur because of an acute reduction in availability of the major adrenal steroid hormone, dehydroepiandrosterone (DHEA) in people who already produce low levels. My primary hypothesis is DHEA optimizes transcription and replication of DNA. Therefore, all tissues are activated by DHEA. It follows that DHEA activates the brain. Therefore, consciousness is a function of times of high DHEA and sleep is a time of low DHEA. I think cortisol, the second major adrenal steroid hormone, evolved to counteract the effects of DHEA during aggressive, potentially harmful or lethal, conflicts. Antagonism of DHEA by cortisol may be the basis of "fight or flight," which has high survival value. Cortisol production causes stress. The ratio of DHEA to cortisol should affect all tissues, especially neurological tissues, and becomes pathological in individuals who experience panic attacks.

Cortisol is involved in panic attacks. One study of panic attacks reported "subtle but significant elevation of cortisol levels" compared to controls, however, these levels did not correlate significantly with the severity of panic attacks (Bandelow, et al., 2000a). A subsequent study found nocturnal cortisol levels tend to be higher and "occurred mainly in more severely ill panic patients." (Bandelow, et al., 2000b). Another study confirms lack of high cortisol levels with all panic attacks, i.e., plasma cortisol was elevated only during some attacks (Cameron, et al., 1987). Cortisol is connected to panic attacks, but cortisol levels, alone, do not cause panic attacks

Cholecystokinin (CCK) increases cortisol and provokes panic attacks, even in some healthy subjects. "In seven subjects, cholecystokinin-4 provoked a short-lasting (one to four minutes) panic-like attack (an intense unexplainable fear) at doses between 20 and 100 micrograms. In the other three subjects, doses of 80 to 100 micrograms induced severe anxiety, but no panic-like attack." (de Montigny, 1989). A larger study of healthy individuals of two different age groups (20-35 years- and 65-81 years-old) treated with CCK found "cortisol was significantly greater with CCK than with placebo," but the cortisol levels "were not correlated with symptom severity, suggesting that other factors may have contributed to the differential effect of panic on the HPA axis." (Flint, et al., 2000). In patients with panic disorder, CCK consistently stimulated panic attacks identical to spontaneous panic attacks (Bradwejn, et al., 1990).

Prolactin production increases during spontaneous panic attacks and panic attacks induced by CCK (de Montigny, 1989). In the study of CCK in healthy adults of differing ages, Flint, et al., found that "maximum increase in prolactin, ACTH and cortisol was significantly greater with CCK," compared to placebo (Flint, et al., 2000). More importantly, prolactin correlates with the severity of spontaneous panic attacks. "Plasma prolactin was elevated at the peak of most of the attacks and correlated with attack severity." (Cameron, et al., 1987). Prolactin levels are directly tied to panic attacks and their severity.

I suggest the increase in prolactin during spontaneous panic attacks and during "panic-like attacks in healthy volunteers" induced by CCK (de Montigny, 1989) represent a mechanism for increasing DHEA during attacks. In young baboons, prolactin specifically stimulates DHEA: "in contrast to ACTH, the action of PRL [prolactin] on the adrenal is apparently specific for androgen [DHEA] production." (Pepe, 1985). Hyperprolactinemia occurs with elevated DHEAS in women. When hyperprolactinemia is reduced with bromocriptine, DHEAS levels are reduced without changes in cortisol levels (Schiebinger, et al., 1986). Reducing prolactin reduces DHEAS. (DHEA sulfate, DHEAS, is the large supply of DHEA available in blood. The active molecule, DHEA, is derived from this supply.) >P? Fava, et al., measured the ratio of DHEAS to cortisol in panic disorder. They examined this ratio because the ratio had "been used as an index of adrenocortical function, [they hypothesized the ratio] would be altered in panic disorder patients and would change after treatment." They reported "No significant differences were noted between pretreatment and posttreatment DHEA-S/cortisol ratio values in patients treated with alprazolam(n = 8), in patients treated with clonazepam (n = 13), or in patients treated with placebo (n = 3)." Of importance to this treatise is their finding that "The DHEA-S/cortisol ratio values in the 24 patients with panic disorder (mean = 20.5, SD = 11.6) were significantly higher than those of a group of 60 normal controls (mean = 11.5, SD = 6.01) and were also significantly higher than those of a group of 22 depressed patients (mean = 10.6, SD = 6.33)." (Fava, et al., 1989)

If one assumes that DHEA is the active molecule, the findings of Fava, et al., may be explained. Patients with panic disorder may produce significantly less DHEA than controls and depressed patients because panic attack patients are not producing DHEA from DHEAS, so their DHEAS to cortisol ratio is very high. Fava, et al., also found no differences when their patients were treated with alprazolam. However, Kroboth, et al., report that alprazolam increases DHEA significantly in "healthy volunteers (25 young men, aged 22-35, and 13 elderly men, aged 65-75)." "Alprazolam produced (1) significant increases in DHEA concentrations at 7 hours in both young and elderly men; (2) significant decreases in cortisol concentrations; and (3) no change in DHEA-S concentrations." (Kroboth, et al., 1999). The lack of change in DHEAS levels may suggest the conversion from cortisol to DHEA in healthy individuals.

DHEA reduces prolactin levels (Milewich, et al., 1995). A sufficiently high level of DHEA inhibits prolactin production. This is a cyclic mechanism involving prolactin and DHEA. Healthy individuals produce sufficient DHEA to reduce prolactin levels. Patients with panic attack disorder who produce very low DHEA cannot reduce prolactin by feedback inhibition from DHEA. This is why "Plasma prolactin was elevated at the peak of most of the attacks and correlated with attack severity." (Cameron, et al., 1987).

It is my hypothesis that DHEA stimulates consciousness during the day and declines at night, to allow sleep. During sleep, I think DHEA declines to lowest levels during delta (slow-wave) sleep, with levels maintained just sufficient to support cardiovascular activity. This level is maintained by the cyclic mechanism involving prolactin. When DHEA declines to low levels, prolactin increases and stimulates sufficient DHEA to maintain the brainstem. When this cycling occurs, DHEA levels overshoot and decrease prolactin. This extra DHEA stimulates the brain. This slight increase in DHEA during sleep activates the brain and produces REM sleep or dreaming. Therefore, according to my model of sleep, delta sleep represents a time of low DHEA and REM sleep represents a time of higher DHEA during sleep. Kronenberg, et al., administered CCK to healthy subjects during REM sleep and delta sleep. CCK produced panic attack-like effects of greater intensity during the time of lowest DHEA, that is, delta sleep. "In nine subjects, stimulation with 50 µg CCK-4 during REM sleep failed to elicit a full-blown panic awakening, while the same dose, administered during delta sleep, produced full-blown panic attacks in two participants. Similarly, stimulation of six subjects with 100 µg CCK-4 during REM sleep resulted in only one panic response, whereas four of nine subjects awoke experiencing a panic attack following stimulation with the identical dose during delta sleep. Severity of panic symptomatology, as measured by the self-rated Acute Panic Inventory, was also significantly increased when CCK-4 was administered during delta sleep." (Kronenberg, et al., 2001). This study supports a connection of low DHEA with panic attacks. Since Bandelow, et al., 2000b, found higher levels of nocturnal cortisol in "more severely ill panic patients" and Abelson and Curtis also reported "overnight hypercortisolemia" in panic disorder (Abelson and Curtis, 1996), this could indicate conversion from DHEA to cortisol in panic disorder.

Panic attacks may be due to very low DHEA levels relative to cortisol levels, possibly resulting from conversion of DHEA to cortisol. Therefore, normal levels of cortisol may predispose an individual to panic attacks even without a triggering event. If cortisol levels are high relative to DHEA between attacks, the individual may experience intermittent or continuous anxiety. Therefore, any latent physiological or psychological change which increases the cortisol to DHEA ratio could excite a panic attack. Prolactin levels increase during panic attacks and are directly connected to severity. Prolactin increases to stimulate DHEA. Since prolactin levels are decreased by DHEA and panic attack sufferers cannot produce sufficient DHEA, prolactin levels remain high and connected with the panic attack. Panic attacks result from the inability to respond to excess cortisol relative to DHEA.



Res. 1989; 28: 345-50.

Um dont know if you two realized this or not but no one has posted in this thread in 5 years