Posted by Tomatheus on November 27, 2005, at 22:55:00
In reply to Depression caused by immune system?, posted by Mistermindmasta on November 27, 2005, at 21:14:55
Mistermindmasta,
See below for my responses to to sections of your post...
> Does anyone agree with the idea that depression is caused by the immune system? After doing hours and hours and hours of endless reading books and online researching, I am essentially convinced that most mental illness is CAUSED by the immune system.
I think that there is evidence to support the idea that abnormalities in the immune system are very likely part what causes depression (and potentially other mental illnesses) in some cases. But are immune system abnormalities the cause of *most* cases of mental illness? I doubt it.
> I do not believe immune system activation is caused by depression. It is, in my opinion, most definitely the other way around.
I think there is evidence that it could work both ways.
> I do not believe depression is directly related to imbalances in serotonin, dopamine, norepinephrine or any of the bigger name peptides that are being researched.
I think there is evidence that, in some cases, genetically mediated abnormalities of various mechanisms connected to neurotransmitter functioning (e.g., destructive enzymes, reuptake pumps, and receptor sites) are part of what causes depression. When scientists seek to establish a causal relationship between variables, the question that they ask is "which one came first?" Even though there is clear evidence that environmental factors (which could potentially include viruses and toxins that cause disease) are part and parcel of the cause of psychiatic illnesses, I think it is important to examine genetic abnormalities - especially in cases when environmental factors seem to play less of a role - when examining causative factors of mental illness because it is indeed our genes that come first. As I have mentioned in other posts, genetic variations that encode for abnormal functioning of several mechanisms in the serotonin, norepinephrine, and dopamine systems have shown statistically significant associations with psychiatric illnesses. Many of these relationships have been replicated in multiple studies. So, I do think that there is evidence that genetically mediated abnormalities of the neurotransmitter systems are part of what causes psychiatric illnesses -- in some cases. But are these the only genetic variants that have shown statistically significant associations with psychiatric illnesses? Absolutely not. And are genetic causes the *only* causes of mental illness. Of course not. In the diathesis-stress model of explaining the causes of mental illnesses, genetic factors only represent the diathesis.
> I believe activation of components of the immune system by some sort of bacterial / viral / fungal component is the CAUSE of (most) mental illness, by indirectly altering the sensitivity of glutocorticoid receptors and also indirectly altering the monoamines mentioned above.
Once again, I do think that there is evidence that the factors you mention likely contribute to the causation of psychiatic illnesses in some cases, but I don't think that there is evidence to support the statement that these factors cause *most* mental illnesses.
> A lot of recent studies show that interleukins and interferon alpha cause behavior identical to depression. And interestly, a lot of antidepressants might work NOT through serotonin or norepinephrine, but by inhibiting interleukin 6 or tumor necrosis factor alpha. St. John's Wort, for example, is thought by some to relieve depression through lowering IL-6 levels; this, they believe, is the first and foremost action that allows antidepressant activity. Secondary actions, though not related to antidepressant activity, are reuptake of all monoamines, glutamate, gaba, alteration of sodium channels, etc. Do the research on pubmed.org. See what you find. Or go to google. Type "IL-6 depression" or "St. John's Wort IL-6".
Yes, you're absolutely right. This is interesting research material. I am personally aware of the relationship between IL-6 levels and depression (although I understand that many users here are probably not, and I'm glad that you pointed it out). And yes, I think there is definitely strong evidence that amino acids, cytokines, and hormones exert indirect actions on the levels of neurotransmitters. As you pointed out, a lot of research studies have focused on the relationship between psychiatric illnesses and factors such as the levels of amino acids and cytokines. I personally would like to see more research done in these areas, and I think researchers should pay particular attention to trying to better understand the causal role that cytokines and amino acids play in psychiatric illnesses.
> Isn't it weird that most of our depressions are accompanied by feelings of true sickness?? We often feel SICK, not just depressed. I know from my experience, most of what doctors would have called depression was actually me feeling sick. I was depressed because I felt sick. Initially, my main symptom was continuous nausea.
This is interesting. From what I have read, I don't think that most depressive patients experience continuous nausea as their initial main symptom, but I don't doubt what you're saying at all. I thank you for sharing your experience. It just goes to show me how different all of our experiences are (and implies that depression is vastly heterogeneous; in other words, there is no single factor that is the cause of *most* depressions).
> Most of us have pain syndromes or IBS, especially. Yet doctors say the pain syndromes are from not enough norep and serotonin going around, so you take antidepressants. But yet, antidepressants are often direct anti-inflammatory agents by lowering cytokines like IL-6, not necessarily through altering serotonin.
Yes, you're right. Oftentimes, that is true.
> Cytokines have been shown to cause a wide variety of memory deficits, attentional deficits, mood alterations and can cause anxiety. People with mood disorders show substantial increases in these same cytokines. For example: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16199015&query_hl=
>
> This study shows that a medication for HIV, efavirenz, increases interleukin-1 beta and tumor necrosis factor alpha. This medication also causes fatigue, insomnia and depression so severe that some people get suicidal. And what do they use to LOWER LEVELS OF THESE CYTOKINES? Paroxetine. Paroxetine prevented increases of the pro inflammatory cyokintes and alleviates the depression:
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16166808&query_hl=1
>
> Does it not seem entirely plausible that people who have increased ENDOGENOUS cytokines might also be experiencing increased endogenous depression?Yes. Actually, it is more than just plausible. Consider this study on the relationship between dysthymia and abnormal variants of the IL-alpha, IL-1beta, and IL-RA genes (but remember that dysthymia is believed to be heterogeneous and that these genetic variants are probably present in some, but not all, cases of dysthymia):
> So what else causes increased inflammatory cytokines besides this antiviral medication mentioned above? Here's an answer:
>
> Within our small and large intestine, we have a slew of bacteria that are generally symbiotic or harmless. Sometimes, the balance of bacteria gets altered so that more inflammation causing bacteria are present, which often happens in IBS. Keep in my mind that people with IBS often have depression or anxiety. Anyway, when the balance of bacteria gets altered so that more pathogenic bacteria are present, inflammatory cytokine levels start to get higher. Studies have been done in people with IBS where they supplement their diet with probiotics - the good bacteria - and symptoms of their IBS improves. At the same time, the pro inflammatory cytokines decrease.
>
> So...
>
> People with IBS have abnormal bacteria which causes increased pro inflammatory cytokines... These same cytokines can cause cognitive and mood dysfunction... And antidepressants in fact lower levels of pro inflammatory cytokines, which correlates with clinical improvement... people with depression often feel TRULY sick...Yes, you are correct.
> Maybe we are! Doesn't it seem like there actually IS a sickness here, not just some delusional beliefs and distorted anxieties leading to bowel dysfunction!
Maybe. Your theory could potentially explain some cases of depression, but I am not convinced that IBS is associated with depression in a majority of cases.
> I don't mean to sound like my theory is 100% fact, because in reality, there just aren't enough studies that link one thing to the other to the other the way I have. However, I do have a lot of confidence in the validity of this theory and I'm not afraid to show it. Let me put things this way: I've been a hardcore pubmed research nut for 4 years old, initially for my IBS symptoms and now also for my brain dysfunction. I have hundreds and hundreds of studies printed out with notes on the side. As I watch various research on probiotics, IBS and antidepressants pile up, I only become more and more convinced of the truth of my theory. Pieces, here and there add up in my mental memory. I'll make the rather bold statement that in 20 years, you'll see antidepressants that function DIRECTLY by altering cytokine profiles.
I hope you're right. I personally think that there is a dire need for more antidepressants that have a primary mechanism of action of doing something other than inhibiting the reuptake of serotonin, norepinephrine, and/or norepinephrine.
> In addition, you will see "depression" being cured through the use of altering the bacterial, fungal and viral populations in the body. Indeed, depression is genetic in part, as researchers will tell you. BUT, mostly in the response to bacteria / fungus / viruses and the brain's response to cytokines. Some people respond to interferon alpha therapy with suicidal depression. Some people feel fine. THAT'S genetics.
Yes, but the genes that have been associated with cytokine levels are not the only genes that have been associated with depression. But in with some cases of depression, it is possible that you may be right.
> Also, I must conclude by saying that there are, of course, other mechanisms by which the brain enters a state of dysfunction. Nutritional deficiencies can cause this. Environmental toxins can contribute. Inappropriate emotional reactions to events in one's life, etc. But most importantly, we must all take a closer look at our own immune systems if we want to see whats REALLY going on most of the time!
You're absolutely right!
Tomatheus
poster:Tomatheus
thread:582826
URL: http://www.dr-bob.org/babble/20051126/msgs/582865.html