Supressing HPA axis and endocrine basis for depression

[streetsurfer]

From what I know that an overactive HPA axis and a hyper adreanal state in the brain is strongly linked to depression . What I want to know is are there any practical interventions as far as novel treatments for depression go?

I am totally shooting from the hip here and my understanding of neuroscience leaves alot to be desired but as far as I can tell depression seems to be basicly an endocrine disease??

Thoughts?

Endocrine disturbances in depression.

Tichomirowa MA, Keck ME, Schneider HJ, Paez-Pereda M, Renner U, Holsboer F, Stalla GK.

Max-Planck-Institute of Psychiatry, Munich, Germany. [email protected]

Depression is one of the most common psychiatric disorders. For a long time, clinicians suspected a causal link between depression and the endocrine system. The most frequently occurring endocrine abnormality in depressed subjects is hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. CRH and AVP are likely to play a substantial role in the pathophysiology of this disorder, and their receptors appear to be a specific target for future antidepressant drugs. Depression also affects the hypothalamic-pituitary-GH (HPGH) and -thyroid (HPT) axes. Alterations in the reproductive system may also play a role in the pathology of depression. In addition, there is increasing evidence that leptin and neurosteroids, such as DHEA, are implicated in mood disorders.

The neuroendocrinology of posttraumatic stress disorder: new directions.

Rasmusson AM, Vythilingam M, Morgan CA 3rd.

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. [email protected]

Studies of the hypothalamic-pituitary-adrenal (HPA) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at gamma-aminobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.

I

Depression is characterised by an over activity of the hypothalamic-pituitary-adrenal (HPA) axis that resembles the neuro-endocrine response to stress.? These HPA axis abnormalities participate in the development of depressive symptoms.? Moreover, antidepressants directly regulate HPA axis function.? These novel findings are reshaping our understanding of the causes and treatment of this disabling disorder.


Major depression – major importance


Costing more than 30 billion pounds every year in the UK and the US alone, major depression is a significant cause of disability and the most important cause of suicide worldwide.? Why should neuro-endocrinologists bother with depression?? Depression is characterised by an over activity of the hypothalamic-pituitary-adrenal (HPA) axis that resembles the neuro-endocrine response to stress.? In this Briefing I will claim that HPA axis hyperactivity is not a mere epiphenomenon of depression, but rather a crucial biological mechanism in the pathogenesis of this disorder and a fundamental target for its successful treatment.


HPA axis activity is governed by the secretion of corticotropin-releasing hormone (CRH) from the hypothalamus.? CRH activates the secretion of adrenocorticotropic hormone (ACTH) from the pituitary.? ACTH, in turn, stimulates the secretion of glucocorticoids (cortisol in humans) from the adrenal glands.? Glucocorticoids interact with their receptors - the corticosteroid receptors - in almost every tissue in the body, and the best known effect is the regulation of energy metabolism.? By binding to corticosteroid receptors in the brain, glucocorticoids also inhibit the further secretion of CRH from the hypothalamus and ACTH from the pituitary (negative feedback).


Three lines of evidence demonstrate the link between stress, depression and the HPA axis.? First, depression, in its core symptoms of dysphoric or low mood, inability to take pleasure and low energy, is a universal cross-cultural response to stressful events, particularly when the stress is chronic or the individual has no control over the situation.? Second, stress activates the HPA axis, leading to a powerful release of glucocorticoids into the bloodstream; depression, especially when severe, is also characterised by over activity of the HPA axis.? Third, treatments that modify the stress response, like “talking therapies” improving the ability to cope with stress, have an antidepressant effect; moreover, known antidepressants directly decrease HPA axis activity.


Facts and questions


The HPA axis abnormalities in patients with major depression are remarkably similar to those present in animals experiencing chronic stress.? Depressed patients have an increased drive to the HPA axis, as shown by the larger production of CRH in the brain.? They also have an impaired negative feedback by glucocorticoids.? Finally, they have an increased volume of the adrenal and pituitary glands.? One accepted explanation for the HPA axis over activity in depression is that, because of the reduced function of the corticosteroid receptors, circulating cortisol is unable to successfully inhibit HPA axis activity (“glucocorticoid resistance”). Consistent with this, antidepressants directly increase the expression and function of corticosteroid receptors in the brain, thus enhancing the negative feedback and reducing HPA axis activity.


“One? way to conceptualise depression is a pathological stress response gone awry”...Charles B. Nemeroff, 1996
?


There is, however, a big unanswered question (see Figure).? Does the fact that depressed patients have a hyperactive HPA axis actually mean that a lot of cortisol is flooding their brain, and that the depressive symptoms are consequence of this putative “toxic” effect of cortisol (Pathway A)?? Or is the opposite true: that patients have a hyperactive HPA axis as a compensatory mechanism, because their brain is resistant to the effects of circulating cortisol (Pathway B)?? The question is not trivial, especially in our quest for a more effective treatment.? In the first scenario, our recommendation should be the lowering of cortisol levels.? In the second scenario, our recommendation should be the administering of more cortisol.? The situation is complicated by the fact that increased cortisol levels in the bloodstream do not necessarily translate into increased effects of glucocorticoids on the brain, because the brain sensitivity to cortisol is also regulated by the function of the corticosteroid receptors as well as by efflux systems at the blood-brain barrier.? In what seems to be a clear effort of nature to tease us all, depression has been described in endocrine disorders characterised by elevated cortisol levels, like Cushing’s disease, but also in disorders characterised by low cortisol levels, like Addison’s disease.? Moreover, high and low levels of cortisol give similar functional and morphological changes in the brain.? Even more strikingly, both the lowering of cortisol levels and the administering of cortisol have antidepressant effects in depressed patients.



Two hypothetical pathways by which the activation of the HPA axis participates in the development of depression. In Pathway A, the elevated levels of cortisol induce the depressive symptoms (as in Cushing?s disease). In Pathway B, the lack of effects of cortisol induces the depressive symptoms (as in Addison?s disease). See text.
Hero or villain?


Why should the stress-induced activation of the HPA axis, a biological system that is life saving and enables us to fight or escape our enemy, lead to such a bad thing as depression?? The answer, from an evolutionary point of view, is that depression - if you are a fawn in a cold barren land, or a defeated gorilla that has fallen in the dominance hierarchy - is an adaptive response.? Depression stops you dispersing energy in the pursuing of unavailable goals, prevents further aggressive behaviour from the dominant animals, and signals your difficulty.? Today, an increasing number of researchers believe that the stress-induced HPA axis activation directly causes depressive symptoms, by interacting with the brain neurotransmitter systems regulating these behavioural changes.? This idea is further supported by clinical studies showing that normalization of HPA activity by antidepressants precedes the therapeutic effects on the depressive symptoms.? While the exact mechanism of this effect is still unknown - and we are divided on whether cortisol is a hero or is a villain - the galloping development in this research field is already changing our understanding of neurobiology and our clinical practice.

Last Updated ( Tuesday, 14 June 2005 )
Depression is characterised by an over activity of the hypothalamic-pituitary-adrenal (HPA) axis that resembles the neuro-endocrine response to stress.? These HPA axis abnormalities participate in the development of depressive symptoms.? Moreover, antidepressants directly regulate HPA axis function.? These novel findings are reshaping our understanding of the causes and treatment of this disabling disorder.


Major depression – major importance


Costing more than 30 billion pounds every year in the UK and the US alone, major depression is a significant cause of disability and the most important cause of suicide worldwide.? Why should neuro-endocrinologists bother with depression?? Depression is characterised by an over activity of the hypothalamic-pituitary-adrenal (HPA) axis that resembles the neuro-endocrine response to stress.? In this Briefing I will claim that HPA axis hyperactivity is not a mere epiphenomenon of depression, but rather a crucial biological mechanism in the pathogenesis of this disorder and a fundamental target for its successful treatment.


HPA axis activity is governed by the secretion of corticotropin-releasing hormone (CRH) from the hypothalamus.? CRH activates the secretion of adrenocorticotropic hormone (ACTH) from the pituitary.? ACTH, in turn, stimulates the secretion of glucocorticoids (cortisol in humans) from the adrenal glands.? Glucocorticoids interact with their receptors - the corticosteroid receptors - in almost every tissue in the body, and the best known effect is the regulation of energy metabolism.? By binding to corticosteroid receptors in the brain, glucocorticoids also inhibit the further secretion of CRH from the hypothalamus and ACTH from the pituitary (negative feedback).


Three lines of evidence demonstrate the link between stress, depression and the HPA axis.? First, depression, in its core symptoms of dysphoric or low mood, inability to take pleasure and low energy, is a universal cross-cultural response to stressful events, particularly when the stress is chronic or the individual has no control over the situation.? Second, stress activates the HPA axis, leading to a powerful release of glucocorticoids into the bloodstream; depression, especially when severe, is also characterised by over activity of the HPA axis.? Third, treatments that modify the stress response, like “talking therapies” improving the ability to cope with stress, have an antidepressant effect; moreover, known antidepressants directly decrease HPA axis activity.


Facts and questions


The HPA axis abnormalities in patients with major depression are remarkably similar to those present in animals experiencing chronic stress.? Depressed patients have an increased drive to the HPA axis, as shown by the larger production of CRH in the brain.? They also have an impaired negative feedback by glucocorticoids.? Finally, they have an increased volume of the adrenal and pituitary glands.? One accepted explanation for the HPA axis over activity in depression is that, because of the reduced function of the corticosteroid receptors, circulating cortisol is unable to successfully inhibit HPA axis activity (“glucocorticoid resistance”). Consistent with this, antidepressants directly increase the expression and function of corticosteroid receptors in the brain, thus enhancing the negative feedback and reducing HPA axis activity.


“One? way to conceptualise depression is a pathological stress response gone awry”...Charles B. Nemeroff, 1996
?


There is, however, a big unanswered question (see Figure).? Does the fact that depressed patients have a hyperactive HPA axis actually mean that a lot of cortisol is flooding their brain, and that the depressive symptoms are consequence of this putative “toxic” effect of cortisol (Pathway A)?? Or is the opposite true: that patients have a hyperactive HPA axis as a compensatory mechanism, because their brain is resistant to the effects of circulating cortisol (Pathway B)?? The question is not trivial, especially in our quest for a more effective treatment.? In the first scenario, our recommendation should be the lowering of cortisol levels.? In the second scenario, our recommendation should be the administering of more cortisol.? The situation is complicated by the fact that increased cortisol levels in the bloodstream do not necessarily translate into increased effects of glucocorticoids on the brain, because the brain sensitivity to cortisol is also regulated by the function of the corticosteroid receptors as well as by efflux systems at the blood-brain barrier.? In what seems to be a clear effort of nature to tease us all, depression has been described in endocrine disorders characterised by elevated cortisol levels, like Cushing’s disease, but also in disorders characterised by low cortisol levels, like Addison’s disease.? Moreover, high and low levels of cortisol give similar functional and morphological changes in the brain.? Even more strikingly, both the lowering of cortisol levels and the administering of cortisol have antidepressant effects in depressed patients.



Two hypothetical pathways by which the activation of the HPA axis participates in the development of depression. In Pathway A, the elevated levels of cortisol induce the depressive symptoms (as in Cushing?s disease). In Pathway B, the lack of effects of cortisol induces the depressive symptoms (as in Addison?s disease). See text.
Hero or villain?


Why should the stress-induced activation of the HPA axis, a biological system that is life saving and enables us to fight or escape our enemy, lead to such a bad thing as depression?? The answer, from an evolutionary point of view, is that depression - if you are a fawn in a cold barren land, or a defeated gorilla that has fallen in the dominance hierarchy - is an adaptive response.? Depression stops you dispersing energy in the pursuing of unavailable goals, prevents further aggressive behaviour from the dominant animals, and signals your difficulty.? Today, an increasing number of researchers believe that the stress-induced HPA axis activation directly causes depressive symptoms, by interacting with the brain neurotransmitter systems regulating these behavioural changes.? This idea is further supported by clinical studies showing that normalization of HPA activity by antidepressants precedes the therapeutic effects on the depressive symptoms.? While the exact mechanism of this effect is still unknown - and we are divided on whether cortisol is a hero or is a villain - the galloping development in this research field is already changing our understanding of neurobiology and our clinical practice.

Last Updated ( Tuesday, 14 June 2005 )


http://www.neuroendo.org.uk/content/view/31/11/

Low doses of dexamethasone can produce a hypocorticosteroid state in the brain.

Karssen AM, Meijer OC, Berry A, Sanjuan Pinol R, de Kloet ER.

Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, The Netherlands.

The synthetic glucocorticoid dexamethasone (dex) blocks stress-induced hypothalamic-pituitary-adrenal (HPA) activation primarily at the level of the anterior pituitary because multidrug resistance P-glycoprotein hampers its penetration in the brain. Here, we tested the hypothesis that central components of the HPA axis would escape dex suppression under conditions of potent peripheral glucocorticoid action. We subchronically treated rats with low or high doses of dex. The animals were subjected on the last day of treatment for 30 min to a restraint stressor after which central and peripheral markers of HPA axis activity were measured. Basal and stress-induced corticosterone secretion, body weight gain, adrenal and thymus weight, as well as proopiomelanocortin mRNA in the anterior pituitary were reduced in a dose-dependent manner by dex administered either 5 d sc or 3 wk orally. In the brain, the highest dose dex suppressed CRH mRNA and CRH heteronuclear RNA in the paraventricular nucleus (PVN). However, in the peripherally active low-dose range of dex CRH mRNA and heteronuclear RNA showed resistance to suppression, and CRH mRNA expression in the PVN was in fact enhanced under the long-term treatment condition. In the PVN, c-fos mRNA was suppressed by the highest dose of dex, but this effect showed a degree of resistance after long-term oral treatment. c-fos mRNA responses in the anterior pituitary followed those in PVN and reflect central drive of the HPA axis even if corticosterone responses are strongly reduced. The results support the concept that low doses of dex can create a hypocorticoid state in the brain.

Reserch on vassopressin
but what is really interesting is oxytocin. Is there any reason why I shouldn't try it? Or just any other thoughts would be appreciated thanks

http://www.ncbi.nlm.nih.gov/entrez/..._uids=14675803&query_hl=7&itool=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/...uids=10102788&query_hl=12&itool=pubmed_docsum


Oxytocin modulates neural circuitry for social cognition and fear in humans.

http://www.ncbi.nlm.nih.gov/entrez/...uids=16339042&query_hl=14&itool=pubmed_docsum

Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice.

http://www.ncbi.nlm.nih.gov/entrez/...uids=16249339&query_hl=14&itool=pubmed_docsum

## Spun out studies like this...

Oxytocin is associated with human trustworthiness.

http://www.ncbi.nlm.nih.gov/entrez/...uids=16109416&query_hl=14&itool=pubmed_DocSum

G'night Y'all

 

[BilZ0r]

Yeah, the old immuno-theory of depression..

This idea you've got reminds of an article out in PLoS medicine
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030208

Basically, the Author is ragging on the idea that all diseases are caused by a loss of homeostasis, e.g. ideas like depression is caused by low serotonin, or an over active HPA axis etc...

Depression correlates with lots of shit, IQ, weight, hippocampal volume etc... but that doesn't mean it causes any of them, of they cause depression...

...But no, I don't know of any way to reduce HPA activation safely off the top of my head.

 

[streetsurfer]

ok, but just out of interest consider this..

Differential effects of acute and chronic social defeat stress on hypothalamic-pituitary-adrenal axis function and hippocampal serotonin release in mice.

Keeney A, Jessop DS, Harbuz MS, Marsden CA, Hogg S, Blackburn-Munro RE.

Psychopharmacological Research, H. Lundbeck A/S, Copenhagen, Denmark.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) stress axis and disturbances in serotonin (5-HT) neurotransmission have been implicated in the pathogenesis of depressive disorder. Repeated social defeat of male NMRI mice has been shown to induce increases in core body temperature and corticosterone, indicative of a state of chronic stress in subordinate animals. The present study further characterised the HPA axis response to social defeat stress, and also examined hippocampal extracellular 5-HT release during the stress. Exposure to an acute social defeat elicits increases in plasma adrenocorticotrophic hormone and corticosterone levels, peaking at 15 and 30 min, respectively, and enhances corticotrophin-releasing factor (CRF) mRNA, but not arginine vasopressin (AVP) mRNA within the medial parvocellular division of the hypothalamic paraventricular nucleus. A concomitant increase in hippocampal corticosterone and 5-HT levels is observed. By contrast, although chronic social defeat is associated with greatly elevated corticosterone levels, the predominant drive appears to be via parvocellular AVP rather than CRF. Furthermore, subordinate animals allowed to recover for 9 days after chronic social defeat display an increase in immobility in the forced swimming model of depression, indicating that animals previously exposed to the homotypic defeat stress are sensitised to the behavioural effects of a novel stressor. These results demonstrate that social defeat induces prolonged activation of the HPA axis and alterations in 5-HT neurotransmission that could be of relevance to some of the pathological abnormalities observed in clinical depression.

Dynamics and mechanics of social rank reversal.

Summers CH, Forster GL, Korzan WJ, Watt MJ, Larson ET, Overli O, Hoglund E, Ronan PJ, Summers TR, Renner KJ, Greenberg N.

Biology and Neuroscience, University of South Dakota, 414 East Clark Street, Vermillion, SD 57069-2390, USA. [email protected]

Stable social relationships are rearranged over time as resources such as favored territorial positions change. We test the hypotheses that social rank relationships are relatively stable, and although social signals influence aggression and rank, they are not as important as memory of an opponent. In addition, we hypothesize that eyespots, aggression and corticosterone influence serotonin and N-methyl-D: -aspartate (NMDA) systems in limbic structures involved in learning and memory. In stable adult dominant-subordinate relationships in the lizard Anolis carolinensis, social rank can be reversed by pharmacological elevation of limbic serotonergic activity. Any pair of specific experiences: behaving aggressively, viewing aggression or perceiving sign stimuli indicative of dominant rank also elevate serotonergic activity. Differences in the extent of serotonergic activation may be a discriminating and consolidating factor in attaining superior rank. For instance, socially aggressive encounters lead to increases in plasma corticosterone that stimulate both serotonergic activity and expression of the NMDA receptor subunit 2B (NR(2B)) within the CA(3) region of the lizard hippocampus. Integration of these systems will regulate opponent recognition and memory, motivation to attack or retreat, and behavioral and physiological reactions to stressful social interactions. Contextually appropriate social responses provide a modifiable basis for coping with the flexibility of social relationships.

PMID: 15372303 [PubMed - indexed for MEDLINE]

 

[streetsurfer]

Endocrine disturbances in depression.

Tichomirowa MA, Keck ME, Schneider HJ, Paez-Pereda M, Renner U, Holsboer F, Stalla GK.

Max-Planck-Institute of Psychiatry, Munich, Germany. [email protected]

Depression is one of the most common psychiatric disorders. For a long time, clinicians suspected a causal link between depression and the endocrine system. The most frequently occurring endocrine abnormality in depressed subjects is hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. CRH and AVP are likely to play a substantial role in the pathophysiology of this disorder, and their receptors appear to be a specific target for future antidepressant drugs. Depression also affects the hypothalamic-pituitary-GH (HPGH) and -thyroid (HPT) axes. Alterations in the reproductive system may also play a role in the pathology of depression. In addition, there is increasing evidence that leptin and neurosteroids, such as DHEA, are implicated in mood disorders.

Publication Types:
Review

PMID: 15816377 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/...uids=15816377&query_hl=12&itool=pubmed_docsum

 

[streetsurfer]

So you don't think homeostatix interventions like below carry any credence?
What is your take on depression BilZ0r? My current thinking is that it is evolutionary based biological changes in the brain brought on by the environment that corrolates with changes in various brain systems WHICH I belive can be pharmacetically or biologically reverse engineered to the state of mind that we desire ie. happy, domminent, agressive, smart, sensitive etc etc
yada yada

Biological rhythm disturbances in mood disorders.

Wirz-Justice A.

Centre for Chronobiology, Psychiatric University Clinics, Basel, Switzerland. [email protected]

From earliest times, psychiatrists have described biological rhythm disturbances as characteristic of mood disorders. The present flourishing of circadian biology has revealed the molecular basis of 24-h rhythmicity driven by 'clock' genes, as well as the importance of zeitgebers (synchronisers). Winter depression was first modelled on regulation of animal behaviour by seasonal changes in daylength, and led to application of light as the first successful chronobiological treatment in psychiatry. Light therapy has great promise for many other disorders (e.g. sleep-wake cycle disturbances in Alzheimer's dementia, bulimia, premenstrual disorder, depression during pregnancy) and, importantly, as an adjuvant to antidepressant medication in major non-seasonal depression. The pineal hormone melatonin is also a zeitgeber for the human circadian system, in addition to possessing direct sleep-promoting effects. Chronobiology has provided efficacious non-pharmaceutical treatments for mood disorders (such as sleep deprivation or light therapy) as well as novel approaches to new drugs (e.g. agomelatine).

PMID: 16436934 [PubMed - in process]

 

[streetsurfer]

Nobody is replying to me so I am going to keep posting studies along this line until someone convinces me this is a dead end of enquiry.
As it stands, what is at the core of depression? The seritonin hypothasis has been disproven as has the monomine amise theory..... Neurogenesis??? That seems to largly regulated by hormonal influences also.
Thoughts?

Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics.

Marx CE, Stevens RD, Shampine LJ, Uzunova V, Trost WT, Butterfield MI, Massing MW, Hamer RM, Morrow AL, Lieberman JA.

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA. [email protected]

Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics. We therefore investigated neuroactive steroid levels in post-mortem brain tissue from subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects to determine if neuroactive steroids are altered in these disorders. Posterior cingulate and parietal cortex tissue from the Stanley Foundation Neuropathology Consortium collection was analyzed for neuroactive steroids by negative ion chemical ionization gas chromatography/mass spectrometry preceded by high-performance liquid chromatography. Subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects were group matched for age, sex, ethnicity, brain pH, and post-mortem interval (n = 14-15 per group, 59-60 subjects total). Statistical analyses were performed by ANOVA with post-hoc Dunnett tests on log transformed neuroactive steroid levels. Pregnenolone and allopregnanolone were present in human post-mortem brain tissue at considerably higher concentrations than typically observed in serum or plasma. Pregnenolone and dehydroepiandrosterone levels were higher in subjects with schizophrenia and bipolar disorder compared to control subjects in both posterior cingulate and parietal cortex. Allopregnanolone levels tended to be decreased in parietal cortex in subjects with schizophrenia compared to control subjects. Neuroactive steroids are present in human post-mortem brain tissue at physiologically relevant concentrations and altered in subjects with schizophrenia and bipolar disorder. A number of neuroactive steroids act at inhibitory GABA(A) and excitatory NMDA receptors and demonstrate neuroprotective and neurotrophic effects. Neuroactive steroids may therefore be candidate modulators of the pathophysiology of schizophrenia and bipolar disorder, and relevant to the treatment of these disorders.

PMID: 16319920 [PubMed - in process]

Full article
http://www.nature.com/npp/journal/v28/n3/full/1300084a.html

 

[streetsurfer]

Supressing hpa axis

Comparison of the effects of Sho-hange-ka-bukuryo-to and Nichin-to on human plasma adrenocorticotropic hormone and cortisol levels with continual stress exposure.

Katagiri F, Inoue S, Sato Y, Itoh H, Takeyama M.

Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Japan. [email protected]

Sho-hange-ka-bukuryo-to and Nichin-to, traditional Chinese herbal (Kampo) medicines have been used to treat vomiting and nausea. Traditional herbal medicines have frequently been used in the empirical treatment. Some patients who take these medicines have no organic disease but have conditions classified as non-ulcer dyspepsia (NUD). To determine the pharmacological effects of Sho-hange-ka-bukuryo-to, Nichin-to, and the two herbs (Pinelliae Tuber and Zingiberis Rhizoma, both of which are included in Sho-hange-ka-bukuryo-to and Nichin-to), we examined the effects of these medicines on the plasma levels of adrencorticotropic hormone (ACTH) and cortisol under stress conditions by repetitive blood sampling. After a single administration of Kampo medicine or a placebo, venous blood samples were taken before and 20-240 min after administration. A single administration of Sho-hange-ka-bukuryo-to caused significant suppression of an increase in plasma ACTH-immunoreactive substance (IS) levels at 120 to 180 min and tended to suppress increases in plasma cortisol levels at 240 min, compared with the response to a placebo. A single administration of Nichin-to caused significant suppression of increases in plasma ACTH-IS levels at 120 min compared with a placebo group, but had no effect on plasma cortisol levels. Pinelliae Tuber had no significant effects in plasma ACTH-IS or cortisol, but Zingiberis Rhizoma significantly suppressed the increase of ACTH-IS (120 min) and cortisol (180 min). These medicines have a modulatory effect on the hypothalamo-pituitary-adrenal (HPA) axis and autonomic nervous function. These effects might be beneficial in stress-related disease and suggest that this medicine has clinical pharmacological activity.

 

[BilZ0r]

Neurogenisis is an interesting angle, but it's not the be all and end all. A recent paper showed that the antianxiety effect of environment enrichment (which I think is related to antidepressant effect) is independent of the neurogensis stimulating properties of excersise http://www.ncbi.nlm.nih.gov/entrez/..._uids=16648847&query_hl=8&itool=pubmed_docsum