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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 98. This is the beginning of the thread.
Posted by Trotter on December 19, 2012, at 23:44:21
I found this thesis very interesting. It confirmed a lot of my own thinking about how a high fat diet combined with pathogenic intestinal bacteria leads to systemic inflammation. (sorry about the untidy link)
This online book is all about how systemic inflammation causes depression.
http://www.cytokines-and-depression.com/
Put the two together and what do you get? A high fat diet causes -> inflammation -> depression.
Some other research is also very interesting as it seems bifidobacteria may provide an antidote from the HFD -> inflammation. I hypothesize that the bifidobacteria attach to the bowel wall and prevent translocation of LPS from the pathogenic bacteria. The HFD seems to reduce bifidobacterial numbers, but this can be reversed by consuming oligofructose prebiotic.
Posted by SLS on December 20, 2012, at 7:27:04
In reply to High fat diet -) inflammation -) depression, posted by Trotter on December 19, 2012, at 23:44:21
In most cases, I am inclined to view brain inflammation as a consequence of depression rather than its cause. However, once the immune system is triggered by depression, I should think that it would make the depression more severe or treatment-resistant. There might be a sort of positive feedback loop operating. Not good. Of course, systemic inflammation is another story. Sometimes, an infection can trigger or make worse a depressive episode in people who already have MDD or BD. I have seen this occur on multiple occasions.
- Scott
Posted by Trotter on December 20, 2012, at 13:22:29
In reply to Re: High fat diet -) inflammation -) depression, posted by SLS on December 20, 2012, at 7:27:04
The thesis I linked to in my previous post proved a causal link between high fat diet, invasive bowel bacteria and systemic inflammation. The following trials in mice provide strong causal link between high fat diets and depression. When taken together, this is further evidence of a causal relationship between inflammation and depression. That said, I'm sure you are right that people who already suffer from depression are more likely to suffer worse when experiencing systemic inflammation.
http://psychcentral.com/news/2012/05/28/high-fat-diet-linked-to-depression-anxiety-in-mice/39295.html
http://www.sciencedaily.com/releases/2012/12/121212092104.htm
Posted by SLS on December 20, 2012, at 15:09:26
In reply to Re: High fat diet -) inflammation -) depression » SLS, posted by Trotter on December 20, 2012, at 13:22:29
> The thesis I linked to in my previous post proved a causal link between high fat diet, invasive bowel bacteria and systemic inflammation. The following trials in mice provide strong causal link between high fat diets and depression. When taken together, this is further evidence of a causal relationship between inflammation and depression. That said, I'm sure you are right that people who already suffer from depression are more likely to suffer worse when experiencing systemic inflammation.
>
> http://psychcentral.com/news/2012/05/28/high-fat-diet-linked-to-depression-anxiety-in-mice/39295.html
> http://www.sciencedaily.com/releases/2012/12/121212092104.htm
>I still don't see a causal relationship being established here. Your first citation mentions the word inflammation once and indicates a line or reasoning why it is related to high-fat diets. However, the connection being made between inflammation and depression is still a correlate without proof of causation. It is a rather tenuous link to other people's work in that they pose the hypothesis that it "may lead to"...
"Other research has shown that food high in saturated fat such as hamburgers, bacon, pork sausages, cheese, butter, and ice cream cause inflammation in the body, including the brain, and that this inflammation may lead to negative mood states."
The second citation doesn't mention inflammation at all.
I am not willing to jump on the "inflammation causes depression" bandwagon just yet.
I don't know why diets high in animal fat and obesity are associated with depression. Is inflammation the common denominator? According to your citations, it seems as if changes in reward center activation, sensitivity, and gene expression are considered causal. Perhaps I am misinterpreting the articles.
- Scott
Posted by Trotter on December 20, 2012, at 18:13:44
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 20, 2012, at 15:09:26
I think you missed my point. The thesis I linked in an earlier post proves that high fat diet causes inflammation. Those last two links were not presented as proof that inflammation causes depression, but that high fat diet causes depression. My argument is that if high fat diet causes inflammation, and high fat diet causes depression, then it is highly likely the chain of events is high fat diet -> inflammation -> depression. I agree it isn't conclusive that this is the process, but when taken along with all the other evidence linking inflammation to depression I think the argument is pretty compelling.
You are of course aware that there are lots of cases where pro-inflammatory cytokines have been provoked in animals and humans and that depressive symptoms have resulted. Surely this is cause and effect?
Posted by SLS on December 20, 2012, at 18:44:35
In reply to Re: High fat diet -) inflammation -) depression » SLS, posted by Trotter on December 20, 2012, at 18:13:44
> You are of course aware that there are lots of cases where pro-inflammatory cytokines have been provoked in animals and humans and that depressive symptoms have resulted.
Actually, I am not aware of this.
Provoked by what? Stress response?
- Scott
Posted by Trotter on December 20, 2012, at 23:18:23
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 20, 2012, at 18:44:35
> > You are of course aware that there are lots of cases where pro-inflammatory cytokines have been provoked in animals and humans and that depressive symptoms have resulted.
>
> Actually, I am not aware of this.
>
> Provoked by what? Stress response?
>
>
> - Scott"Marshall et. all cite several studies connecting depression with increased levels of TNF alpha, IL-1, and IL-6 in cerebrospinal fluid of test subjects injected with an endotoxin, similar to levels in severely depressed patients."
http://serendip.brynmawr.edu/bb/neuro/neuro06/web1/jengelman.html
"In addition, administration of proinflammatory cytokines, e.g. in cancer or hepatitis C therapies, has been found to induce depressive symptomatology. Administration of proinflammatory cytokines in animals induces 'sickness behaviour', which is a pattern of behavioural alterations that is very similar to the behavioural symptoms of depression in humans"
http://www.ncbi.nlm.nih.gov/pubmed/15694227
"IL1 given to animals or humans triggers a deluge of whole body responses. IL1 causes: sleep, fever, inflammation, pain, malaise, aching joints, fatigue; irritability, depressed mood, social withdrawal, lack of interest in things,"
"Cytokines given chronically (i.e. more than 10 days) result in a different set of symptoms. Fever is usually not present. Varying combinations of neuropsychiatric symptoms are usually more prominent, such as, fatigue, loss of interest in things, apathy, inability to concentrate, poor attention span, headache, irritability, anxiety and depression. In most subjects, the symptoms are mild, but in almost all the experiments, between 10 and 50% of the subjects report severe and debilitating symptoms"
http://www.cytokines-and-depression.com/chapter5.html
"The profound effects of cytokines on mood, thought and behavior were first discovered in the early 1980's. For the first time in history, physicians had found molecules made by the human body which, when given to humans, produced all the symptoms necessary for the diagnosis of depression."
"A few year later Rohatiner et al.6 published a more detailed study. They gave INFα intravenously for seven days to eleven volunteers and observed the effects. All volunteers became feverish, fatigued and lacked appetite. They were socially withdrawn, slow to answer questions, lost interest in their surroundings and slept most of the day. In one week, these volunteers developed nearly all the symptoms necessary for the diagnosis of major depressive episode"
"A year later, Adams et al.7 did a longer term (four week, ten patient) study on the effects of INFα. For the first few days fever, headache, aching muscles and other flu like symptoms occurred, but they did not persist. They were replaced by symptoms of severe depression."
"In a more recent clinical study, Niiranen et al.8 gave high dose intravenous INFα to nine cancer patients for five days, followed by a lower intra muscular dose three times a week. None of the patients had prior neurological or psychiatric disease and just prior to treatment with interferon all patients were judged to be mentally healthy. After initiating INFα therapy, neuropsychiatric abnormalities developed gradually. Very interestingly, on the second day, "a short-lasting but clear euphoric phase was seen. Patients were in a heightened mood and abnormally hopeful, resembling mania." The depressive symptoms begin appearing on the third day. All volunteers exhibited fatigue, lack of appetite, lack of interest, slowed movement and thought, clumsiness, excessive sleep and all but one was irritable (two very severely) and confused. Very severe depressed mood affected five out of nine and anxiety was reported by three volunteers. This clinical study confirmed the ability of INFα to produce all the symptoms necessary for the diagnosis of major depressive episode. Notable in this trial was the irritability and depressed mood exhibited by the majority of the patients."
"McDonald, Mann and Thomas9 published a paper in 1987 in the Lancet titled 'Interferons as Mediators of Psychiatric Morbidity'. This was a controlled trial of 43 hepatitis B patients, in which 29 patients were given INFα three times weekly for up to six months. Most of the patients on INFα reported fatigue, loss of interest, lack of concentration, anxiety and depression. Control patients not given INFα did not report these symptoms. An amazing 63% of the volunteers on interferon became psychiatric patients!"
"Human volunteers given TNF intravenously develop many neuropsychiatric symptoms. Fatigue, anorexia, headache, muscle ache and malaise were the most common symptoms reported13,14,15 Essentially TNF makes a person feel lousy, just like someone with major depression feels."
"IL1 is primarily secreted by monocytes and macrophages. The effects of IL1 on behavior has only been studied in laboratory animals. Laboratory animals exhibit "sickness behavior" when given IL1. Sickness behavior includes symptoms like anorexia, reduced activity, loss of interest in usual activities, malaise, increased sleep, lack of body-care activities, reduced social exploration and less food-motivated behavior.20 These behaviors are considered an adaptive response to infection and they are very similar to the behaviors found in human depression"
"Recently, monkeys were given IL1 in a quiet setting followed later by an experimenter entering the room and having direct eye contact with the monkey.21 During the quiet setting, without the experimenter in the room, the monkeys showed typical sickness behavior, that is, less activity, less exploration, fewer vocalizations and more sleep. Then the experimenter entered the room and made direct eye contact with the monkeys. This is considered a socially stressful situation for the monkeys. Very interestingly, the monkeys given IL1 exhibited more agitation, more threatening behavior and more anxiety when the experimenter made eye contact than the animals not given IL1. Therefore, under non-stressful social conditions, IL1 produces sickness behavior. But under stressful social conditions, IL1 produces anxious, irritable and hostile behavior. This is very significant, because anxious, irritible and hostile behavior is very common in depressed persons. In fact, irritability is a DSM-IV symptom of depression."
"Low doses of IL-2 produce symptoms of depression. Severe lethargy, impaired memory, slowed responses, impaired attention, anorexia, lack of interest and irritability are found with most volunteers after receiving low doses of IL2. High doses of IL2 provoke very severe symptoms of schizophrenia, including hallucinations, delusions, disorientation in time, place or person.22 These observations have prompted the development of a macrophage-lymphocyte model of schizophrenia.23,24,25"
"INFγ given to humans usually provokes fatigue, malaise, headache, lack of appetite, weight loss, weakness, lethargy and decreased concentration.26,27 All of these are common symptoms of depression."
http://www.cytokines-and-depression.com/chapter7.htmlDid you realise that most, if not all, antidepressants have anti-inflammatory action?
Posted by SLS on December 21, 2012, at 8:07:33
In reply to Re: High fat diet -) inflammation -) depression » SLS, posted by Trotter on December 20, 2012, at 23:18:23
Hi.
Thanks for taking the time to post the citations and quotes. I have not read them all yet.
> Did you realise that most, if not all, antidepressants have anti-inflammatory action?
>
> http://www.ncbi.nlm.nih.gov/pubmed/18580840Fact: depression and stress have pro-inflammatory actions. It makes sense that an *effective* antidepressant treatment would reduce the inflammation these stressors trigger. The article you cited does nothing more than associate depression with inflammation. It does not demonstrate causality.
"...are causally related to depression (following external (psychological) and internal (organic) stressors."
They pretty much proved my point here without realizing it. Stress leads to depression. Although they use the word "causality", they do not demonstrate it.
The authors made no attempt to offer a biological mechanism by which an antidepressant drug exerts an anti-inflammatory effect. They simply have not proved causality in their paper - only association. My suggestion (and it is only a suggestion) would explain all of their observations as easily as theirs would.
I really do think that:
Chronic (psychosocial or systemic) stress > depression > inflammation > more depression > more inflammation > more depression > etc.
If I didn't think that inflammation were an important component to the *persistence* and worsening of depressive illness, I wouldn't bother taking drugs like minocycline. I am convinced that chronic stress produces brain inflammation. Actually, if I could draw a tree here, I would also place inflammation as a secondary component of the stress response via excess cortisol secretion, eventually merging with the main line and leading to a worsening of the depression that had already been triggered.
You might want to look into the relationship between glial cells (including microglia) and inflammation. Once triggered (by stress or depression), they produce pro-inflammatory cytokines. So, here we have a measurable observation of a stressed brain tissue actually causing inflammation - not the other way around.
http://www.ncbi.nlm.nih.gov/pubmed/23051934
We are talking about affective disorders here - Major Depressive Disorder (MDD) and Bipolar Disorder (BD). I am sure that drugs like interferon, interleukin, and other immune system activators can make someone feel depressed, much as I have placed inflammation in my diagram. However, they do not trigger the MDD or BD diseases processes. When you discontinue the offending pro-inflammatory drug, the feelings of depression disappear. Thus, the drug has not produced MDD or BD.
- Scott
Posted by Trotter on December 21, 2012, at 13:29:52
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 21, 2012, at 8:07:33
Hmm...
You may well be right that chronic stress causes depression. Without having researched it, I would be surprised if chronic stress was not a factor in causing depression.
I also have little doubt that one's genetic makeup is also a factor in depression. There are probably lots of things that can cause depression. After all, depression is only a collection of symptoms.
However I think I have produced compelling evidence that inflammation causes depression. And back to the topic of this thread I believe that I have presented strong evidence that a high fat diet causes inflammation and this inflammation causes depression.
Posted by jono_in_adelaide on December 21, 2012, at 19:13:59
In reply to Re: High fat diet -) inflammation -) depression » SLS, posted by Trotter on December 21, 2012, at 13:29:52
Omega 3 fatty acids are reputed to help depression and reduce inflamation - a good reason to add a decent dose of fish oil to ones intake of pills
Posted by SLS on December 21, 2012, at 19:59:06
In reply to Re: High fat diet -) inflammation -) depression » SLS, posted by Trotter on December 21, 2012, at 13:29:52
> Hmm...
>
> You may well be right that chronic stress causes depression.Perhaps in some cases.
> However I think I have produced compelling evidence that inflammation causes depression.
Perhaps in some cases.
> And back to the topic of this thread I believe that I have presented strong evidence that a high fat diet causes inflammation and this inflammation causes depression.
Perhaps in some cases.
As you have noted:
> "There are probably lots of things that can cause depression. After all, depression is only a collection of symptoms"
I don't dispute here that there are depressions that are the result of inflammation. However, I have a problem with any statement that suggests that all depressions are caused by inflammation.
A sick organ tells the immune system to come to the rescue (via cytokines, etc.). Why would the brain be such an exception? Only here, the sickness is MDD or BD.
I am not yet compelled by the work of the authors you have so far presented. Perhaps I will change my mind, but I would really need to see a diagram or model of a hypothetical cascade of biological events from start to finish that begins with inflammation and leads to MDD or BD.
- Scott
Posted by SLS on December 21, 2012, at 20:39:28
In reply to Re: High fat diet -) inflammation -) depression, posted by jono_in_adelaide on December 21, 2012, at 19:13:59
> Omega 3 fatty acids are reputed to help depression and reduce inflamation - a good reason to add a decent dose of fish oil to ones intake of pills
It is hard to argue against that. However, Carlson's fish oil makes me feel decidedly worse.
I think there might be something pharmacological going on with high-dose omega-3 whereby depression is ameliorated by mechanisms more immediate to the site of mood dysregulation than is the reduction of brain inflammation. Some people actually become manic immediately after taking their first dose of fish oil. To me, that seems far to quick to be explained by a reduction in inflammation. Of course, one (me) could argue that O3FA might facilitate a reduction in inflammation by removing the stress that produces it. That stress very well might be the depression itself.
O3FA > (membrane stability / CREB / BDNF) > reduced depressive stress > reduced inflammation.
I guess arguments could be made either way.
Some people suggest that when there are multiple explanations for a phenomenon, the simplest one is probably the right one. I think that inflammation is an attractive explanation to account for depression for precisely this reason. There are times when it is attractive to me, too.
- Scott
Posted by Trotter on December 21, 2012, at 21:18:49
In reply to Re: High fat diet -) inflammation -) depression, posted by SLS on December 21, 2012, at 20:39:28
Personally I think fish oil works for some people because it has an anti-inflammatory action. This is not just because I believe that inflammation causes depression. You see the main 'good' fatty acids in fish oil are DHA and EPA. Of the two, only EPA seems to be effective in reducing depression. I don't think it's a coincidence that of the two, EPA is also the only one that reduces inflammation.
Posted by jono_in_adelaide on December 21, 2012, at 21:20:46
In reply to Re: High fat diet -) inflammation -) depression, posted by SLS on December 21, 2012, at 20:39:28
I agree SLS, there are a lot of ifs, buts and maybes in there
Posted by Trotter on December 21, 2012, at 21:25:13
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 21, 2012, at 19:59:06
Actually, I am not saying that inflammation is the sole cause of depression. I have never said that. I know that some 'experts' believe that is the case, but I'm not saying that. All I'm saying that there is overwhelming evidence that inflammation can cause depression in susceptible people. The same goes for stress, high fat diets etc etc.
> > Hmm...
> >
> > You may well be right that chronic stress causes depression.
>
> Perhaps in some cases.
>
> > However I think I have produced compelling evidence that inflammation causes depression.
>
> Perhaps in some cases.
>
> > And back to the topic of this thread I believe that I have presented strong evidence that a high fat diet causes inflammation and this inflammation causes depression.
>
> Perhaps in some cases.
>
> As you have noted:
>
> > "There are probably lots of things that can cause depression. After all, depression is only a collection of symptoms"
>
> I don't dispute here that there are depressions that are the result of inflammation. However, I have a problem with any statement that suggests that all depressions are caused by inflammation.
>
> A sick organ tells the immune system to come to the rescue (via cytokines, etc.). Why would the brain be such an exception? Only here, the sickness is MDD or BD.
>
> I am not yet compelled by the work of the authors you have so far presented. Perhaps I will change my mind, but I would really need to see a diagram or model of a hypothetical cascade of biological events from start to finish that begins with inflammation and leads to MDD or BD.
>
>
> - Scott
>
Posted by Trotter on December 21, 2012, at 21:32:40
In reply to Re: High fat diet -) inflammation -) depression, posted by jono_in_adelaide on December 21, 2012, at 21:20:46
I advocate 1g EPA/day. Try to avoid too much DHA as they 'compete' with each other. The only successful trials involving fish oil for depression have involved at least 7:1 EPA to DHA. Some 'experts' advise taking up to 4g EPA or more, but in the only trial of various doses, the most effective was 1g.
Posted by SLS on December 21, 2012, at 23:35:21
In reply to Re: High fat diet -) inflammation -) depression » jono_in_adelaide, posted by Trotter on December 21, 2012, at 21:32:40
> I advocate 1g EPA/day. Try to avoid too much DHA as they 'compete' with each other. The only successful trials involving fish oil for depression have involved at least 7:1 EPA to DHA. Some 'experts' advise taking up to 4g EPA or more, but in the only trial of various doses, the most effective was 1g.
If I were to return to fish oil, I would take Omegabrite.
- Scott
Posted by SLS on December 22, 2012, at 1:16:11
In reply to Re: High fat diet -) inflammation -) depression » SLS, posted by Trotter on December 21, 2012, at 21:18:49
> I don't think it's a coincidence that of the two, EPA is also the only one that reduces inflammation.
I agree with most of what you have to say.
To help bolster your argument, you might want to look into the association between BDNF and inflammation.
It is known that chronic stress is associated with lower BDNF levels, increased cortisol levels, and reductions in hippocampal volume. More recently, inflammation has been observed to be present under these conditions. I would like to see a proposed physiological mechanism that would explain how inflammation may decrease BDNF levels directly, and that this not be mediated through the actions of increased cortisol at the cellular level. It is important to determine the directionality of the associations between cortisol and inflammatory markers. Perhaps the chronic elevation of cortisol produces cortisol-resistance and thereby allows inflammation to occur.
It is possible that you are right about everything. Right now, I am a hard sell.
- Scott
Posted by jono_in_adelaide on December 22, 2012, at 1:16:21
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 21, 2012, at 23:35:21
I just take generic 1000mg fish oil capsules, 4 a day..... I take it for general health benifits, but if it helps my mental state as well, all the better
Posted by SLS on December 22, 2012, at 1:26:05
In reply to Re: High fat diet -) inflammation -) depression, posted by jono_in_adelaide on December 22, 2012, at 1:16:21
> I just take generic 1000mg fish oil capsules, 4 a day..... I take it for general health benifits, but if it helps my mental state as well, all the better
Do you have any ideas as to why some people feel worse when they take fish oil? For me, Carslson's makes me feel worse (bipolar depression). I tried it twice as a rechallenge just to be sure. Perhaps more interesting is why some people become activated or manic as an immediate reaction to the initial doses of fish oil. It is hard to believe that inflammation would be reduced so instantaneously as to allow some sort of rebound mania. Perhaps something more pharmacological than nutritional is going on.
- Scott
Posted by Trotter on December 22, 2012, at 1:34:06
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 21, 2012, at 23:35:21
> > I advocate 1g EPA/day. Try to avoid too much DHA as they 'compete' with each other. The only successful trials involving fish oil for depression have involved at least 7:1 EPA to DHA. Some 'experts' advise taking up to 4g EPA or more, but in the only trial of various doses, the most effective was 1g.
>
> If I were to return to fish oil, I would take Omegabrite.
>
>
> - ScottThat's what I buy.
Posted by Trotter on December 22, 2012, at 1:43:14
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 22, 2012, at 1:16:11
> It is possible that you are right about everything. Right now, I am a hard sell.
>
>
> - Scott
You are a hard sell! But it has been good to debate because it's forced me to update my own references. Cheers.
Posted by jono_in_adelaide on December 22, 2012, at 2:03:04
In reply to Re: High fat diet -) inflammation -) depression » jono_in_adelaide, posted by SLS on December 22, 2012, at 1:26:05
No idea scott, but i suspect it must be somthing of a drug like reaction - i remember reading that evening primrose oil can increase or cause seizures in people prone to epilepsy, so I dont see why fish oil causing mania etc shoulsd be impossible
To be honest, fish oil hasnt done anything for my mood either way, I mainly take it for general nutritional support because I dont like fish and never eat it
Posted by SLS on December 22, 2012, at 7:39:03
In reply to Re: High fat diet -) inflammation -) depression, posted by Trotter on December 22, 2012, at 1:43:14
>
> > It is possible that you are right about everything. Right now, I am a hard sell.
> >
> >
> > - Scott
>
>
> You are a hard sell! But it has been good to debate because it's forced me to update my own references. Cheers.
Here is another VERY good study to add to your collection:http://www.ncbi.nlm.nih.gov/pubmed/22197082
This is one that really makes me think...
- Scott
Posted by Phillipa on December 22, 2012, at 10:27:01
In reply to Re: High fat diet -) inflammation -) depression » Trotter, posted by SLS on December 22, 2012, at 7:39:03
Late to discussion but a compounding pharmacist told me it takes a month to develop some enzyme that allows the fish oil to work. Right or wrong have no idea. He himself takes two. Professional strength forget the brand ran out. Phillipa
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