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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 6 to 30 of 34. Go back in thread:
Posted by linkadge on April 21, 2018, at 15:23:12
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by bleauberry on April 21, 2018, at 10:09:59
I understand what you are saying, but when you talk about "underlying cause" it is likely there are hundreds / thousands of different underlying causes.
Of course, everybody would like to fix their underlying cause, the problem is that they may not be able to identify it, or may not have the means to do so.
There are good bacteria and bad bacteria (in terms of mental health). Suggesting an antibiotic for everybody could make some people worse.
Linkadge
Posted by Christ_empowered on April 21, 2018, at 17:18:47
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by linkadge on April 21, 2018, at 15:23:12
i think status and resources and social connections are powerful "antidepressants," personally.
Posted by Hordak on April 21, 2018, at 17:33:43
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by Christ_empowered on April 21, 2018, at 17:18:47
> i think status and resources and social connections are powerful "antidepressants," personally.
for a man.
For a women it's beauty and youthfulness
Posted by baseball55 on April 21, 2018, at 18:27:30
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by Hordak on April 21, 2018, at 17:33:43
> > i think status and resources and social connections are powerful "antidepressants," personally.
>
> for a man.
> For a women it's beauty and youthfulness
>
>
Not necessarily. Women also crave status, resources and social connections. Poverty is a huge stressor. Low status at work (and resulting sexual harassment and hostile environment) are huge stressors. Loneliness and lack of social connection are huge stressors. Remember that the days when women went to college for their MRS degrees then stayed home and reared children are long gone.
Women work and are out in the world. They earn, on average, 20% less than men due and are discriminated against in many well-paid professions. They deal with constant hostile work situations, child care difficulties, double-shifts (doing all the housework plus working, even if they have a husband at home).
Women today have a lot more to worry about than being pretty and youthful.
Posted by SLS on April 21, 2018, at 21:55:27
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by bleauberry on April 21, 2018, at 8:37:20
> I would just say that maybe another novel approach would be to identify the cause of the "times of stress" and fix that.
Genes + childhood diversity = psychiatric illness.
How would you fix this particular scenario, understanding the realities of our current society?
> Make it so we fix the actual problems so we don't need a protein manipulating drug.
Would you venture a guess as to what these actual problems are?
Borrelia burgdorferi? Nutrition? Genes? Prenatal exposures? Bullying? Learned helplessness? Sexual abuse? Neglect? Stroke? Brain trauma? Substance abuse? Bereavement?
My vote is for "all of the above - and more".
> I mean, I have a question. Our scientists are so brilliant that they can figure out how to manipulate various proteins this way or that way, but they can't figure out what is actually wrong with the person's chemistry?
You are angry at the scientists?
And yes, we do need to manipulate biological functions in order to help people feel better until you or scientists can figure out the rest.
> Why do they focus on downstream but not upstream?
How far upstream would you like to go? Can you provide neuroscience with knowledge so that they can focus their attention there? Are you willing to support scientists or simply rail against them? And while we are here talking about scientists, they are not a monolithic consortium plotting against you and the two doctors you rely upon for your belief system.
As far as I can see, scientists focus on as many things as they can conceive of given the technologies that are available and the knowledge provided to them. Knowledge is always accumulating and evolving. Perhaps you expect too much of today's scientists. They are closer than they were yesterday and further away than they will be tomorrow - as long as science is not stymied by the dogma of demagogues and the disinformation spread by charlatans.
> In any case, the medical world could use some new options in terms of psychiatric medications so hopefully these new discoveries will help to improve the quality of life for some folks.
> > A novel set of antidepressant drugs might be developed that inhibit the actions of TRIP8b. This protein acts during times of stress to suppress activity in the hippocampus via the entorhinal cortex, which is located upstream. The hippocampus is a brain structure involved in mood and memory. When TRIP8b is inhibited, both of these regions become more active. In the laboratory, TRIP8b knock-out mice demonstrated antidepressant behavior and memory-enhancement. I couldn't guess at how long it would take for such compounds to become available - if at all. Some of us will never see them, but our children might.
This isn't a new option?
Hopefully, mankind will be able to help improve the quality of life for all folks.
I always appreciate your enthusiasm.
- Scott
Posted by SLS on April 21, 2018, at 22:01:40
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » bleauberry, posted by SLS on April 21, 2018, at 21:55:27
Correction:
> Genes + childhood diversity = psychiatric illness.
Should be:
Genes + childhood adversity = psychiatric illness.
Sorry.
- Scott
Posted by PeterMartin on April 22, 2018, at 2:44:02
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by linkadge on April 21, 2018, at 15:23:12
A baldness pill would double as an antidepressant for me and I'm sure many other men.
Hard to believe science hasn't figured that one out yet.
(Not to hijack your thread but on the subject of things that seemingly only our children will see)
Posted by linkadge on April 22, 2018, at 7:32:25
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by Christ_empowered on April 21, 2018, at 17:18:47
>i think status and resources and social
>connections are powerful "antidepressants,"
> personally.
I would argue only up to a point. Research shows that income can reduce overall levels of stress / depression but only up to about $70,000 of income a year.
After that income, most people's basic needs are met and buying further toys / goodies / larger house / faster car doesn't create any lasting sense of happiness. Nor does it do anything to ameliorate genetic issues.Also, when wealth is used as a cruch, it may impede recovery in some ways. For example, I would argue that friendships / connections among the rich are perhaps more superficial.
Linkadge
Posted by linkadge on April 22, 2018, at 7:37:10
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by baseball55 on April 21, 2018, at 18:27:30
Much of the "status" effect is learned (i.e. relative deprivation). Many "poor" people still live with resources far above that experienced in other countries.
If I lived in the bush and had a better mud hut than my peers, that might create a constructed feeling of superiority. However, if the base needs are met, the net effect of social status is likely overestimated.
Some studies show that those with higher social status, in fact have higher cortisol levels. This is true in primates where social status positively correlates with cortisol levels.
Social status matters to a point, after which it can itself become a stressor.
"A celebrity is somebody who works their whole life to be noticed, then wears dark sunglasses to avoid being noticed".
Linkadge
Posted by linkadge on April 22, 2018, at 7:45:25
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » bleauberry, posted by SLS on April 21, 2018, at 21:55:27
I've lived in middle (or perhaps lower middle) class my entire life. Some of that may in fact be a result of my depression as opposed to a cause.
I graduated with a 90+ average in high school and with an A+ average in a math / science degree at a respected university. However, I currently earn somewhere between the poverty line and median income.
My illness has perhaps made me complacent. I see that I live in a great country where my base needs are met with a basic job. The only thing worth buying is time / freedom IMHO.
I don't care for status / large house, or other material possessions that people think makes them happy. If celebrities are any proxy for the rich, they sure aren't immune from depression, bipolar, anxiety, alcoholism, drug issues etc.
I have saved quite a bit of money, and I do think that helps relieve stress. However, my day-day life is pretty meagre. I'd be lucky if I spend $100 a year on discressionary items.
That all being said, I'd say I'm living in remission. I don't attribute that to my social status.
Linkadge
Posted by linkadge on April 22, 2018, at 7:50:51
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by PeterMartin on April 22, 2018, at 2:44:02
The problem is the difference between what people perceive will make them happy and what actually makes them happy.
Studies of lottery winners repeatedly show little / lasting effect of winning the lottery on overal level of happiness.
Such studies show that people (over the course of about a year) simply return to their baseline. If they were happy / go lucky, that's what they return to. If they were gouchy, that's what they return to.
It's human nature to believe that obtaining something new / better will improve happiness level. If we didn't think this way, we would not achieve much at all.
Linkadge
Posted by SLS on April 22, 2018, at 8:16:11
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by linkadge on April 21, 2018, at 9:07:10
Hi, Linkadge.
> TRIP8b inhibitors apparently exert their effect through HCN1 channels (no expert here, just google searches).
>
> Ketamine inhibits HCN1. Zinc may also interact with both HCN channels and TRIP8b.Wow. Did you come across anything suggesting that there is a relationship between HCN channels and BDNF production?
> Keep in mind though, that this is the stress induced model of depression. While most people will experience some degree of depression if subjected to enough stress, not all depressive disorders are a result of external stress.
>
> Some researchers argue that focusing on the stress model of depression may be ignoring the underlying cause of a significant group of patients.I had an interesting thought, Linkadge. Regardless of psychosocial stress or biogenic etiologies, depression is itself a stress on the system. If the reaction to this stress is for the brain to increase TRIP8b activity and thus a worsening or persistence of depression, a positive feedback loop is created. Once created, the cycle must be hard to break. Persistent brain inflammation might follow a similar path. Just pondering.
- Scott
Posted by SLS on April 22, 2018, at 8:20:31
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by linkadge on April 22, 2018, at 7:45:25
I hope that you are still improving.
- Scott
Posted by Hordak on April 22, 2018, at 12:10:45
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by PeterMartin on April 22, 2018, at 2:44:02
Big 3 + Seti + needle rolling...
> A baldness pill would double as an antidepressant for me and I'm sure many other men.
>
> Hard to believe science hasn't figured that one out yet.
>
> (Not to hijack your thread but on the subject of things that seemingly only our children will see)
>
Posted by linkadge on April 22, 2018, at 14:19:32
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » linkadge, posted by SLS on April 22, 2018, at 8:16:11
Hi SLS,
Yes, depression is likely a stressor which in turn could end up activating the genes associated with stress induced depression.
However, I remember reading that (at least in rodent studies) the genes associated with the depressive lines of rats were different from the genes associated with stress induced anhedonia / depression.
Linakdge
Posted by linkadge on April 22, 2018, at 14:23:41
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » SLS, posted by linkadge on April 22, 2018, at 14:19:32
Just to add. Sometimes when there are really big stressors in my life, I feel great. I'm not sure if this is a hypomania (or something). It's when the stress ends, and my life goes back to being a meaningless, repetitive sequence of boredom, that I seem incapable of making any changes to.
Linkadge
Posted by linkadge on April 22, 2018, at 16:44:30
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » linkadge, posted by SLS on April 22, 2018, at 8:16:11
As far as your other question, there does seem to be a link between TRIP8b HCN1 and BDNF: See:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418514/Just to add. I am far, far from any expert on this, but (from my reading) there appears to be a whole sequence of events that typically occurs during sucessful 'antidepressant' effects.
Many of the targets, WNT, GSK3, HCN1, TREK, BDNF, mTOR, AMPA (many many others) are all connected in the sucessful treatment of depression. Some are more upstream than others. I.e. a successul treatment with an SSRI may (eventually) activate all the targets mentioned. HCN1 may be part of the pathway, or closer to the final destination (i.e. faster acting) than others.
But, when a treatment works, it is likely associated with alteration of many of these pathways simultanioulsly, or in sequence.
Linkadge
Posted by baseball55 on April 22, 2018, at 18:22:19
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » baseball55, posted by linkadge on April 22, 2018, at 7:37:10
>
> Some studies show that those with higher social status, in fact have higher cortisol levels. This is true in primates where social status positively correlates with cortisol levels.
>
> Social status matters to a point, after which it can itself become a stressor.
Depends on what we mean by status. If status means greater power and authority in the workplace (which is what we generally mean), then the literature is clear. Those with higher status suffer less stress and are less likely to get sick. Researchers in the UK did a survey of civil servants by status/authority level and found that, when exposed to cold viruses, lower level employees were more likely to get sick than their superiors.Yes, we can talk about absolute poverty and how much better off poor Americans are than the poor in Kenya or India. But psychologically, poverty is experiences as a relative condition. To be without a phone, computer, electricity, indoor plumbing, transportation, in the context of US society, represents serious deprivation and huge stress.
>
>
>
Posted by SLS on April 23, 2018, at 0:58:54
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » SLS, posted by linkadge on April 22, 2018, at 16:44:30
> As far as your other question, there does seem to be a link between TRIP8b HCN1 and BDNF: See:
> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418514/Thanks.
> Just to add. I am far, far from any expert on this,You know a heck of a lot more than me!
> but (from my reading) there appears to be a whole sequence of events that typically occurs during sucessful 'antidepressant' effects.
>
> Many of the targets, WNT, GSK3, HCN1, TREK, BDNF, mTOR, AMPA (many many others) are all connected in the sucessful treatment of depression. Some are more upstream than others. I.e. a successul treatment with an SSRI may (eventually) activate all the targets mentioned. HCN1 may be part of the pathway, or closer to the final destination (i.e. faster acting) than others.
>
> But, when a treatment works, it is likely associated with alteration of many of these pathways simultanioulsly, or in sequence.Sounds good to me.
- Scott
Posted by bleauberry on April 23, 2018, at 11:38:48
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » bleauberry, posted by SLS on April 21, 2018, at 21:55:27
>
> Genes + childhood diversity = psychiatric illness.
>
> How would you fix this particular scenario, understanding the realities of our current society?I couldn't speculate on that. What kind of genes? What kind of adversity? What kind of psychiatric illness? You will find some of the people in this imaginary scenario would respond well to Acupuncture, another to an sssri, another to some herbs, and another to simply avoiding gluten.
>
>
> Would you venture a guess as to what these actual problems are?
>
> Borrelia burgdorferi? Nutrition? Genes? Prenatal exposures? Bullying? Learned helplessness? Sexual abuse? Neglect? Stroke? Brain trauma? Substance abuse? Bereavement?The 1st one requires a skilled LLMD and maybe some temporary psych meds. Nutrition is easy to fix. Genetic technology is only in its infancy so it isn't much assistance at this time. The next 3 need a counselor and/or a pastor. Same for substance abuse and bereavement. The substance abuse person might need some medication for about a year. Stroke and brain trauma there really isn't a whole lot we can do except make the person comfortable and as functional as possible.
>
> My vote is for "all of the above - and more".
>
> > I mean, I have a question. Our scientists are so brilliant that they can figure out how to manipulate various proteins this way or that way, but they can't figure out what is actually wrong with the person's chemistry?
>
> You are angry at the scientists?Everybody should be concerned with inadequate science and inadequate medical treatments. Getting angry helps nothing.
>
> And yes, we do need to manipulate biological functions in order to help people feel better until you or scientists can figure out the rest.Armchair quarterbacking at best. Half of the 'manipulations' we assume are doing something could be way off base. Just one of hundreds of examples - zyprexa turns on or up a couple dozen different genes - zyprexa also turns down or off a couple dozen other genes. It also is an antagonist at certain receptors. We automatically deduce that when improvement of mood happens, it is because of something dopamine related or something antagonistic related. But we never even consider that maybe those just make side effects and its the manipulated genes that did the healing. We can discuss manipulating things all day long but a quick glance at the folks at psychobabble immediately tells you that particular approach is unsatisfactory.
>
> > Why do they focus on downstream but not upstream?
>
> How far upstream would you like to go?All the way to the tick bite, to the amalgam filling, to the gluten, to whatever insults the person's body is experiencing. Get rid of all obvious potential insults. Can you provide neuroscience with knowledge so that they can focus their attention there? Are you willing to support scientists or simply rail against them? And while we are here talking about scientists, they are not a monolithic consortium plotting against you and the two doctors you rely upon for your belief system.
I don't agree with your stance of pitting one group against another. They are all supposed to be healing patients but only some of them actually are. Focus on them. Doctors and scientists who are not generally showing patients what remission looks like do not deserve much focus. imo. But I disagree with making a competition about it. The patient is what matters - not theory, not textbooks, not consensus. That's how I view things.
>
> As far as I can see, scientists focus on as many things as they can conceive of given the technologies that are available and the knowledge provided to them. Knowledge is always accumulating and evolving. Perhaps you expect too much of today's scientists. They are closer than they were yesterday and further away than they will be tomorrow - as long as science is not stymied by the dogma of demagogues and the disinformation spread by charlatans.There is way too much disinformation and politics that has corrupted the world of science. Maybe that's why I had to suffer for 20 years without good reason. The CDC is particularly guilty of disinformation, especially in discussions of Lyme, and that is only scratching the surface.
I can literally point my finger at the white coat academia pinheads over at the CDC and blame them directly for losing 20 years of my life to treatment resistant depression. That's because THEY were the ones who instructed MY doctor to tell the patient the DONT HAVE Lyme disease IF THE TEST COMES BACK NEGATIVE! And that is exactly what happened.
>
> > In any case, the medical world could use some new options in terms of psychiatric medications so hopefully these new discoveries will help to improve the quality of life for some folks.In my opinion the next great antidepressant discovery would be a substance that does this: 1.It binds up anything in the blood system that isn't supposed to be there - endotoxins, heavy metals, plastics, undigested foods, stray protein fragments, etc. 2.It provides anti-inflammation from multiple mechanisms and angles. This antidepressant would have nothing to do with agonism, antagonism, reuptake, monoamines, or any of that. It's job would be to remove the most common insults that cause depression, in my opinion.
For example - my case - I walked around for years with endotoxins of Borellia infection hitting my brain receptors and causing psychiatric stuff. Nobody knew. Nobody here even suggested it. But just imagine if there was such a drug that mopped up the endotoxins. You would immediately be able to rule-in or rule-out certain things.
Right now we can't do anything like that. We basically toss a coin in the air and guess at this drug or that drug. And after a few years when we find out that drug is no better than any of its predecessor, we wait with great enthusiasm for the next one. And so it goes, round and round.
Scientists really should be doing a better job helping patients restore wellness. imo I don't mean that in a blanket way for all scientists - primarily the ones in the health field are focusing their expertise on the wrong things, the wrong mechanisms, if you ask me.
>
> I always appreciate your enthusiasm.
>
>
> - Scott
Posted by linkadge on April 23, 2018, at 14:06:55
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » linkadge, posted by baseball55 on April 22, 2018, at 18:22:19
>To be without a phone, computer, electricity, >indoor plumbing, transportation, in the context of >US society, represents serious deprivation and
>huge stress.I disagree. As long as people have a reliable source of food, shelter, clothing and purpose, they will tend to revert to their genetic homeostatis.
People can always look up or look down and be bummed. Again, studies on lottery winners repeatedly show no lasting effect of moving from middle class, to upper class, or upper class to upper, upper class.
I simply cluster with people of a similar socioeconomic status, so that I don't feel relative deprivation.
Again, I was raised middle class, but I am currently living lower class. I have adjusted just fine.
Linkadge
Posted by linkadge on April 23, 2018, at 14:08:39
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by linkadge on April 23, 2018, at 14:06:55
I don't own a cell phone. I've never owned one.
Should I be depressed about this? Never thought about it.
Linkadge
Posted by baseball55 on April 23, 2018, at 19:40:44
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » linkadge, posted by linkadge on April 23, 2018, at 14:08:39
> I don't own a cell phone. I've never owned one.
>
> Should I be depressed about this? Never thought about it.
>
> LinkadgeI didn't say depressed. Just stressed. Without access to a phone (not necessarily a cell phone, though they are actually cheaper today than land-lines), it's hard to find a job or keep a job or arrange child care.
Without electricity, what exactly do people in modern cities due. Burning candles and kerosene is dangerous and often illegal. Your kids can't do their homework at night. You can;t do the housework you need at the end of a long workday.
And yes - adequate food, shelter, clothing, etc can be enough. But what's adequate? In Mumbai, a tiny one room shanty would be more than adequate, since many have no home at all. But that would not be okay in America. In Nigeria, villagers may have only one outfit and will wear it with holes until it completely falls apart. What parent can send a child to school this way in the US/Canada?
I've spent time in some of the poorest places on earth and people are accustomed to a level of deprivation in many parts of the world that would be unthinkable here. Do you think children do not notice, when they go to school, that their classmates have better clothing, more nutritious food, etc.? Do you think they and their parents do not feel stressed by this? People are shamed by relative poverty, especially children and parents. They are stressed trying to make ends meet and nearly failing on a daily basis.
Of course, you live in Canada that has free health care and a bit of a dole. You are a single adult. So things look different to you.
The male privilege always evident on this list has finally, I think, driven me away.
Posted by SLS on April 23, 2018, at 20:01:35
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants., posted by baseball55 on April 23, 2018, at 19:40:44
Hi.
> The male privilege always evident on this list has finally, I think, driven me away.I'm afraid that I am clueless as to what this is.
Please don't go away.
- Scott
Posted by SLS on April 23, 2018, at 20:14:01
In reply to Re: TRIP8b inhibitors? Truly novel antidepressants. » SLS, posted by bleauberry on April 23, 2018, at 11:38:48
I take umbrage to your characterizations of scientists and the state of biological psychiatry.
- Scott
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Dr. Bob is Robert Hsiung, MD,
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