Posted by inmostleaf on October 13, 2008, at 13:14:59
First, thank you to the people who replied to my first post. I really appreciate the thoughtful responses, and especially the thread in regards to HPA dysfunction.
However, I'm still looking to go a little further and hopefully this thread will shed some more light into physiological, biological, and neurological areas.
So...as I stated in the previous thread I was diagnosed with Dysthymic Disorder which seems very similar to PTSD.
From what I've read it seems to me that possibly both can be caused by low dopaminergic & norepinephrine tone over a long period of time (specifically in the mesolimbic pathway), leading an overexpression of GR/MR receptors and increased sensitivity in part in the anterior pituitary, resulting in negative feedback to the adrenals to decrease cortisol secretion. All though it seems there other GR/MR receptors aren't affected by the DA tone of the mesolimbic pathway.
As amphetamine not only acutely fixes that, but also with chronic use leads to sensitization of the mesolimbic pathway to DA (reverse tolerance).
So, in theory it should then also both acutely and chronically resolve the problems with the overexpression and hypersensitivity of the affected GR/MR receptors, leading to eventually a more normalized cortisol state.
Yes, No, Maybe?
At any rate, that's my theory. I would suspect that cardiovascular exercise and its release of endogenous PEA would accomplish something similar, especially if done regularly to increase DA tone via improved calcium transport, but probably at a slower rate due to MAO annihilating PEA.
Lastly, I forgot exactly where I found this info as I copied & pasted into a folder, but I'll try to locate the source. I would like to know what you think of this...
Dysthymia is a mild chronic depressive state where a person never regains a normal mood. It lasts at least 2 years (an arbitrary length of time to allow it to be distinguished from major depressive disorder or adjustment disorders). It can be attributed to psychological, stress, and/or physical health problems.
Thus, dysthymia may occur in neurotransmitter and hormone problems.
This includes conditions with one OR more of the following (oversimplified descriptions):
1. Low Serotonin
2. Low Dopamine
3. Low Norepinephrine
4. Low Testosterone
5. Low Estrogen
6. Low DHEA
7. Low Cortisol
8. Low Progesterone
9. Low Thyroid
10. High Insulin
11. etc. etc.
Note: Recent tests revealed low LH, DHT, Testosterone (free & total), DHEA, Cortistol, a somewhat raised TSH. I also had an MRI done to check for a possible pituitary tumor to exclude Hypogonadism and tests were negative for a tumor. And my testosterone levels have ranged from 335-350 in two tests.
Then I found this via Pubmed...
1: J Affect Disord. 2006 Dec 18;
Plasma testosterone and dehydroepiandrosterone sulfate in male and female patients with dysthymic disorder.
* Markianos M,
* Tripodianakis J,
* Sarantidis D,
* Hatzimanolis J.
Athens University Medical School, Psychiatric Clinic, Eginition Hospital, Vas. Sophias 74, Athens 11528, Greece.
BACKGROUND: Depressive symptomatology has been connected with an activation of the hypothalamus-pituitary-adrenal axis and, in several studies, with reduced androgen levels, while administration of androgens, usually in older subjects, may have positive effects on mood, both in males and females. Regarding dysthymic disorder (DD), low serum testosterone levels have been reported in older males, while information on younger male or on female patients is lacking. METHODS: We assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and cortisol in male and female patients with DD, and compared them to the levels of sex and age matched controls. Eighteen male and 43 female patients in the age range of 22 to 71 years were studied and diagnosed according to the Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups with subjects below or over 50 years of age were also built and compared. RESULTS: Serum T levels were lower than controls mainly in the subjects aged below 50 years, in both genders. More pronounced were reductions in DHEAS levels both in male and female patients, while cortisol levels were normal or reduced. T levels were positively correlated to both DHEAS and cortisol. The negative correlations of DHEAS and T to age were significant for all groups and subgroups, except in the group of male patients. Four male patients (22%) had T levels below 2.0 ng/ml. CONCLUSIONS: Male and female patients with DD aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder.
Interestingly the treatments for dysthymia and PTSD are also similar; some SSRIs and 5-HT(2) antagonists/atypical antipsychotics show the best results, with tricyclics and bupropion not being very effective. The data on St. John's Wort is weak for dysthymia, and nonexistant for PTSD. (which I find odd, as SSRIs and St. John's Wort will both agonize 5-HT(2) receptors... but chronic treatment with paroxetine decreases 5-HT(2) receptor density, though it increases under St. John's Wort)
Given that 5-HT(2) serves an excitatory role, I think PTSD and dysthymia might represent two endpoints on a spectrum of prolonged intrusion/avoidance stress that resolves upon desensitization of the amygdala's hypervigilance long enough to reverse the neuroplastic changes brought about by stress to the amygdala as well as extinction of the stress-linked memories. And blocking the 5-HT(2) receptor seems key here as other catecholamine levels tend to be low in these conditions.
One thing I don't understand though is why psychostimulants are effective for both dysthymia and PTSD. While boosting the abnormally low catecholamine levels probably helps a lot, wouldn't the hypersensitivity to cortisol cause problems?
And the studies which I believe support my aforementioned theory:
"PTSD displays biochemical changes in the brain and body, which are different from other psychiatric disorders such as major depression.
In PTSD patients, the dexamethasone cortisol suppression is strong, while it is weak in patients with major depression. In most PTSD patients the urine secretion of cortisol is low, at the same time as the catecholamine secretion is high, and the norepinephrine/cortisol ratio is increased. Brain catecholamine levels are low, and corticotropin-releasing factor (CRF) concentrations are high. There is also an increased sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis, with a strong negative feedback of cortisol, due to a generally increased sensitivity of cortisol receptors (Yehuda, 2001).
The response to stress in PTSD is abnormal with long-term high levels of norepinephrine, at the same time as cortisol levels are low, a pattern associated with facilitated learning in animals. Translating this reaction to human conditions gives a pathophysiological explanation for PTSD by a maladaptive learning pathway to fear response (Yehuda 2002). With this deduction follows that the clinical picture of hyperreactivity and hyperresponsiveness in PTSD is consistent with the sensitive HPA-axis."
CONCLUSIONS: Male and female patients with DD (dysthymia disorder) aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder.
This case report describes an individual suffering from PTSD who experienced almost complete remission of her symptoms following the prescription of a centrally acting stimulant for unrelated reasons. ... Further investigation of amphetamine-like substances and related compounds in PTSD is required.
These results show that chronic hyperactivity of the CRF system leads to a transient dysfunction of the dopaminergic systems, possibly through oxidative mechanisms, and suggest that stress could be a cofactor in the pathogenesis and/or progression of disorders of the dopaminergic systems.
Our results, together with other reports showing that dopamine inhibits the expression of corticosteroid receptors in the anterior pituitary, suggest that (mesolimbic) dopamine transmission exerts a negative control on central corticosteroid receptors.
They also suggest that long-term changes to a dopamine-sensitive mechanism in prefrontal cortex may contribute to the development of stimulant-induced sensitization of mesolimbic dopamine function.
(I couldn't find a more direct study, but dopaminergic drugs increase DA sensitivity even after discontinuation)
Obtained results indicate that repeated AMPH administration down-regulates GR receptors and increases plasma corticosterone level.
Thank you again for all your time and help.