DHEA Levels and "Stress Burden and Lifetime of Psychiatric Disorder (Depressive and Anxiety Disorders)"
James Michael Howard
jmhoward at arkansas.net
Wed May 5 09:18:31 EST 2004
DHEA Levels and "Stress Burden and Lifetime of Psychiatric Disorder (Depressive
and Anxiety Disorders)" (abstract at end)
Copyright 2004, James Michael Howard, Fayetteville, Arkansas, U.S.A.
I suggest the explanation of the findings of Turner and Lloyd reside in levels
of (dehydroepiandrosterone) DHEA, more precisely, the ratio of cortisol to DHEA.
In 1985 I first suggested low levels of DHEA may result in depression. This has
since been supported and a connection of low DHEA and anxiety has been
demonstrated. Also in 1985, I suggested cortisol, a glucocorticoid, the other
major adrenal steroid hormone, evolved to counteract the actions of DHEA. I
suggested this is the basis of the "fight or flight" mechanism. The cortisol to
DHEA ratio has been recognized as important in a number of mental disorders and
the damaging effects of excessive, prolonged cortisol to neural structures are
well known. (All of this is derived from my principal hypothesis that DHEA was
selected by evolution because it optimizes replication and transcription of DNA.
Therefore, DHEA levels affect all tissues, especially the brain. I think
increases in DHEA levels in evolution produced mammals and their big brains.
"Hormones in Mammalian Evolution," Rivista di Biologia / Biology Forum 2001; 94:
177-184. Cortisol evolved to counteract the positive effect of DHEA on
motivation; cortisol evolved to reduce the negative effects of fighting by
reducing the motivation to fight. If an animal experiences prolonged increases
in the cortisol to DHEA ratio, as is often the case in humans, the loss of
support of DHEA for the brain results eventually in damage to the brain.)
Turner and Lloyd found that "Evidence suggests that high levels of lifetime
exposure to adversity are causally implicated in the onset of depressive and
anxiety disorders." I suggest that, depending upon the growth and development
of the brains of individuals, this may reduce DHEA and, therefore, the function,
and possibly, the structure of their brains. That is, during growth and
development of the brain, levels of DHEA will participate in robust or
less-robust development of the brain. A brain less robust will be more
negatively affected by stress (cortisol) later in life. For example, it is my
hypothesis that schizophrenia results from reduced development of the brain due
to low DHEA and this is why a stressful, precipitating event is often connected
with the onset of schizophrenia around a time when DHEA naturally begins to
decline around age twenty. I suggest this is why schizophrenia often occurs in
the late teens and early twenties. DHEA is known to be low in schizophrenia.
Along a continuum affected by "robustness" of brain development, life
experiences resulting in stress (cortisol), and the cortisol to DHEA level of
the individual, various neuropathies / psychopathies may be exposed.
Individuals whose combination of these results in deviation from "normal," may
result in disorders characterized by a combination of these effects. I suggest
Turner and Lloyd have described this effect in a group which exhibit depression
and anxiety as a result, that is, those whose brains are not reduced to the
level of schizophrenia.
The mechanism I have just described may be demonstrated. While in a system
other than the brain, the much more powerful glucocorticoid, prednisolone,
reduces DHEA levels (Hum Reprod 1999; 14: 1440-4). However, in the brain, it is
known that prolonged treatment with prednisolone significantly reduces brain
volume (Mult Scler 2002; 8: 415-9). This powerful glucocorticoid results in
negative effects on DHEA production and brain structure.
DHEA has been found to be efficacious in schizophrenia: "Our preliminary
observations report for the first time in double-blind fashion the efficacy of
DHEA augmentation in the management of negative, depressive, and anxiety
symptoms of schizophrenia." (Arch Gen Psychiatry 2003; 60: 133-41). An
increased ratio of cortisol to DHEA has been connected with depression:
"Elevated cortisol-DHEA ratios may be a state marker of depressive illness and
may contribute to the associated deficits in learning and memory. Administration
of DHEA or other antiglucocorticoid treatments may reduce neurocognitive
deficits in major depression." (Am J Psychatry 2002; 159: 1237-9). DHEA has
demonstrated anxiety-reducing (anxiolytic) effects (Acta Physiol Scand 1999;
I suggest the findings of Turner and Lloyd result from the same mechanism caused
by prolonged exposure to cortisol that may cause DHEA levels to decline and
negatively affect function and structure resulting in anxiety and depression in
the individuals whom they studied.
Here is the abstract of Turner and Lloyd:
"Stress burden and the lifetime incidence of psychiatric disorder in young
adults: racial and ethnic contrasts," Archives of General Psychiatry 2004; 61:
481-8, R.J. Turner and D.A. Lloyd.
"RESULTS: Level of lifetime exposure to adversity was found to be associated
with an increased risk of subsequent onset of depressive and/or anxiety
disorder. This association remained clearly observable when childhood conduct
disorder, attention-deficit/hyperactivity disorder, prior substance dependence,
and posttraumatic stress disorder were held constant and when the possibility of
state dependence effects was considered. CONCLUSION: Evidence suggests that high
levels of lifetime exposure to adversity are causally implicated in the onset of
depressive and anxiety disorders."
More information about the Neur-sci