4 replies to this topic

[Irishdude]

I have been through this myself multiple times. I have found venlafaxine has killed the associated anxiety and > 50% alleviation of cognitive impairments but not much help with depression.

 

I have yet to try Tianeptine but if I feel like falling off the cliff again, I will order some. Its not available here on Rx. I was diagnosed with ADHD (@ 29 yo) but I don't know if I am truly ADHD or its just the effects of long term depression/anxiety. I was put on Atomoxetine @ 80mg. I've been on that 4 months and I do not see much effect yet on my cognition. Hard to tell. Zero side effects.

 

I would love to understand how long term stress/anxiety/depression impacts the brain and try and counter it. Any suggestions from people who have been through it and recovered?

 

 

Some people on here point to glutamate and the unregulated kappa network.

 

Edited by Irishdude, 19 March 2017 - 11:56 AM.

[Mind_Paralysis]

Stress-induced cognitive decline, without such Depersonalisation/Derealisation symptoms, are not necessarily related to Glutamate and Kappa - they're related to actual, PHYSICAL damage to the brain, caused by excessive cortisol-exposure of the Hippocampus - in essence, what you are describing is BURNOUT, which can be classified as a sort of "depression PLUS".

 

Traditional antidepressants are INEFFECTIVE against the cognitive damage which Burnout causes - the reason is because they only cause a maximum of 5% hippocampal growth! Tianeptine is believed to cause somewhat greater of an effect, but it's unclear how much more - the only drug which would theoretically TRULY give gains here is NSI-189 - 20% hippocampal growth - 4 times more effective! = )

 

I think, what you need to do, is to stop thinking about your stress-induced symptoms as a mental disease, but as an actual PHYSICAL disease - it's actually more akin to the cognitive brain-damage which alcoholics are struck by - those symptoms are also long-term, and very difficult to treat, even after recovery from the alcoholism - the brain-damage will still be there.

 

 

I myself was diagnosed with ADHD-PI at the age of 28 - however, I was not struck with burnout until a few years later, when I tried to TRULY change my life and push forward, no matter the cost, to GET the life I wanted to have, even though my disability stood in my way - the result was catastrophic burnout.

 

A small note regarding Atomoxetine - if you are ADHD-PI it's more likely to help, but if you are just traditional ADHD-C, then it's not likely to help - if you identify more with ADHD-C, then consider shifting to a dopaminergic like DextroAmphetamine instead.

 

I myself do not identify with ADHD-C, at all, in fact, I don't identify with my ADHD-PI diagnosis even! Instead, I identify with a disease called Sluggish Cognitive Tempo - unlike ADHD, SCT is not dopaminergic, it's Norepinephrinergic, hence why I am currently trialling Atomoxetine to treat the symptoms.

 

 

References:

----------------------

Understanding the burnout experience: recent research and its implications for psychiatry

https://www.ncbi.nlm...les/PMC4911781/

 

Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus

https://www.ncbi.nlm...les/PMC4464753/

(slight exercise have been noted as a treatment-option for patients suffering from occupational Burnout here in Scandinavia - the above study confirms WHY that is the case - this region is also, for some reason, the one which is struck the most with the syndrome - perhaps because of genetics)

 

Fear of terror and increased job burnout over time: Examining the mediating role of insomnia and the moderating role of work support

http://onlinelibrary...2/job.1980/full

(problems with insufficient sleep, which nearly EVERY ADHD-er suffers CHRONICALLY from, will also make it harder to recover from the brain-damage)

 

 

Chronic Stress Can Damage Brain Structure and Connectivity

https://www.psycholo...nd-connectivity

 

Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus

http://www.nature.co...mp2013190a.html

 

Traumatic stress: effects on the brain

https://www.ncbi.nlm...les/PMC3181836/

 

Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, and the Hippocampus

http://pediatrics.aa...119/3/509.short

 

The brain and the stress axis: The neural correlates of cortisol regulation in response to stress

http://www.sciencedi...053811909005837

 

(notice how cortisol and the hippocampus is brought up again, and again, and again...)

 

 

Regarding Tianeptine's potentially greater effect on the symptoms than traditional antidepressants:

 

Tianeptine: An Antidepressant with Memory-Protective Properties

https://www.ncbi.nlm...les/PMC2701287/

 

Neurobiological and clinical effects of the antidepressant tianeptine.

https://www.ncbi.nlm...pubmed/18072812

[不滅の]

​On a thread I made a while back I listed a number of symptoms I was experiencing and symptoms like yours seem to be a part of the same spectrum. A loose concensus around here based on the available scientific literature points to cronic inflammation/histamine presence being the primary culprit so looking into this might be beneficial. But I digress. Cronic stress and long-term anxiety disorder is something I share with you. I am no stranger to ADHD symptoms either and I suspect that much of my current cognitive impairment; brain fog, Depersonalisation/Derealisation and depression has to do with the effect of long-term high cortisol production.

​

​Very interesting post by Stinkorninjor, but strong pharmaceuticals are a last resort to me. Wouldn't treating the cortisol problem (rosea, l-theanine, curcumin, excercise, ect.), and promoting NGF (Fish oil, Zinc, Melatonin, Ashitaba, Lion's mane, excercise, ect.) help? What else promotes hippocampus repair?

[Irishdude]

Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression

Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs, and that specific white matter abnormalities are closely associated with MDD onset.  [Nature]

 

Efficacy and tolerability of an mGlu2/3 agonist in the treatment of generalized anxiety disorder.

Abstract

LY354740, a potent and selective mGlu (metabotropic glutamate receptor)2/3 agonist, has shown efficacy in the treatment of generalized anxiety disorder (GAD). LY544344 is a LY354740 prodrug that increases LY354740 bioavailability. This 8-week study was designed to evaluate the efficacy, safety, and tolerability of LY544344 in the treatment of GAD. Participants had a diagnoses of GAD, baseline Hospital Anxiety and Depression Scale anxiety subscale scores > or = 10, and moderate illness severity. Patients were randomized to double-blind treatment with LY544344 16 mg b.i.d. (n = 28), LY544344 8 mg b.i.d. (n = 36), or placebo (n = 44). LY544344 16 mg b.i.d.-treated patients showed significantly greater improvement from baseline in Hamilton Anxiety and Clinical Global Impression-Improvement scores, as well as response and remission rates compared with placebo-treated patients. LY544344 was well tolerated and there were no significant differences in the incidence of treatment-emergent adverse events among the three treatment groups. However, the trial was discontinued early based on findings of convulsions in preclinical studies. In conclusion, the findings of this study support the potential efficacy of mGlu2/3 receptor agonist agents in the treatment of GAD. Additional studies will be needed to further assess the toxicological and clinical profile of LY354740/LY544344. 

 

Edited by Irishdude, 20 March 2017 - 11:02 PM.

[Mind_Paralysis]

 

Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression

Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs, and that specific white matter abnormalities are closely associated with MDD onset.  [Nature]

 

Efficacy and tolerability of an mGlu2/3 agonist in the treatment of generalized anxiety disorder.

Abstract

LY354740, a potent and selective mGlu (metabotropic glutamate receptor)2/3 agonist, has shown efficacy in the treatment of generalized anxiety disorder (GAD). LY544344 is a LY354740 prodrug that increases LY354740 bioavailability. This 8-week study was designed to evaluate the efficacy, safety, and tolerability of LY544344 in the treatment of GAD. Participants had a diagnoses of GAD, baseline Hospital Anxiety and Depression Scale anxiety subscale scores > or = 10, and moderate illness severity. Patients were randomized to double-blind treatment with LY544344 16 mg b.i.d. (n = 28), LY544344 8 mg b.i.d. (n = 36), or placebo (n = 44). LY544344 16 mg b.i.d.-treated patients showed significantly greater improvement from baseline in Hamilton Anxiety and Clinical Global Impression-Improvement scores, as well as response and remission rates compared with placebo-treated patients. LY544344 was well tolerated and there were no significant differences in the incidence of treatment-emergent adverse events among the three treatment groups. However, the trial was discontinued early based on findings of convulsions in preclinical studies. In conclusion, the findings of this study support the potential efficacy of mGlu2/3 receptor agonist agents in the treatment of *GAD*. Additional studies will be needed to further assess the toxicological and clinical profile of LY354740/LY544344. 

 

 

Ah yes, this drug is called EGLUMEGAD - it's not actually intended for improvement in cognition and depression though - it's mainly intended for anxiety (even though, yes, it's shown some effect on depression as well).

 

Last time I checked, you don't seem to suffer from GAD - Generalized Anxiety Disorder anyway, so don't feel too bad about that notice there.

 

Substances which show enhanced stress-tolerance and neurogenic effects, should be where you put most of your money and effort - remember, you have white-matter abnormalities (most likely - your symptoms match those that do).

 

 

As such... like I said... NSI-189 + Tianeptine.

 

Go get!! = )