Even though the idea that inflammation causes depression is not without validity, things have a tendency to go off the rails when it comes to popular explanations for why this might be the case and what should be done about it.
The truth is it isn’t always possible to make a black and white distinction between symptoms and causes, and this is relevant to the relationship between inflammatory processes and mood disorders like depression or anxiety.
“Biomarkers of inflammation (for example, cytokines and C-reactive protein (CRP)) are reliably elevated in depressed patients. Moreover, administration of inflammatory stimuli reduces neural activity and dopamine release in reward-related brain regions in association with reduced motivation and anhedonia.”
Many of the symptoms of stress or metabolic suppression go on to promote further interference with metabolism, and because of this it can sometimes be difficult to work out what caused what.
The good news is that if you take a holistic approach and look for the deeper biological processes capable of driving a number of interrelated problems, it’s possible to see that there are a number of reasons why inflammation is closely associated with depression.
“Magnesium treatment is hypothesized to be effective in treating major depression resulting from intraneuronal magnesium deficits. These magnesium ion neuronal deficits may be induced by stress hormones…”
One recently fashionable suggestion is that an infection of some kind is responsible for the inflammation which then leads to depression. Although this isn’t inconceivable, it’s worth discussing the elements which could be behind the simultaneous promotion of all three of these things and more.
The proper functioning of thyroid metabolism is a central factor protecting against chronic inflammation, as well as potentially being an essential part of the defense against infection and mood dysregulation.
“OS [oxidative stress] seems to be an important mechanism underlying the progress of inflammation. A vicious circle creates a link between these two conditions. Thyroid hormones can have a protective role, modulating antioxidant levels; on the other side, a tissue hypothyroidism can worsen OS.”
Exposure to stress causes blood sugar to be used up at an increased rate and this is more so the case when metabolism is already under functioning. When blood sugar runs low the stress hormones cortisol and adrenalin increase to assist in providing needed energy.
High cortisol has been shown to be involved in the etiology of depression and other varieties of mood disorder.
Increased adrenalin increases the release of polyunsaturated fats into the blood stream causing thyroid suppression and inflammation. The breakdown products of the polyunsaturated fats have been associated with depression and are one of the main things behind chronic blood sugar dysregulation issues.
Both low and high blood sugar can cause an increased susceptibility to infection.
When thyroid function is interfered with, digestion becomes sluggish. Ineffective digestion increases the tendency for bacteria and fungi to grow in number, and move up into the small intestine, where they encourage the release of potentially toxic substances such as bacterial endotoxin.
Endotoxin can directly promote infection, as well as causing serotonin and nitric oxide levels to rise. Serotonin, nitric oxide and endotoxin can both foster inflammation throughout the intestine, and cause interference with mitochondrial energy systems.
This can result in a reduction in intestinal barrier capability, allowing for these (and other) potentially harmful substances to be released in greater amounts into the system, leading to a more generalized inflammatory state and an increasingly chronic level of interference with thyroid and immune system function.
“LPS molecules are potent inflammagens…and may be both cytotoxic and/or neurotoxic…They are known to induce the production of a variety of pro-inflammatory cytokines…Indeed, cytokine production…is central to the development of inflammation…”
Eventually there can be a vicious cycle involving inflammatory materials including endotoxin, circulating iron, the polyunsaturated free fatty acids, the prostaglandins and cytokines and rising levels of stress substances including estrogen, nitric oxide and serotonin.
“…risk factor for developing postinfective IBS …Adverse life events…depression…Clinical conditions with an inflammatory basis…characterised by excess postprandial serotonin release…Several studies report evidence of low-grade inflammation in IBS…”
It can all potentially feed into a chronically blood sugar dysregulated high stress state, increasing susceptibility to many kinds of illness.
Depression is in many ways an energy deficient, hypothermic hibernation-like state, and although the popular belief that serotonin is necessary for happiness is extremely profitable, experimental evidence suggests that high serotonin is a driver of mood instability and inflammation.
Misinterpretations (as well as sometimes misrepresentations) regarding the significance of a few important biochemical processes (like viewing serotonin as something you want to increase rather than decrease) can be enough to prevent the pieces of the puzzle from falling into place.
“The reigning paradigm conceptualizes depression as a state of reduced serotonin transmission…we have reviewed a large body of evidence indicating that the opposite appears to be true. For the depressive phenotypes we have considered—sickness behavior, starvation depression, and melancholia—serotonin transmission to multiple brain regions appears to be elevated…”
Science is now showing that popular antidepressants which increase serotonin levels are not only ineffective in the treatment of depression, they can be responsible for a worsening of symptoms as well as promoting inflammatory disease in general.
Aspirin is known to protect against many of the diseases of stress and inflammation, and has also been demonstrated to have potential anti-depressant, anxiolytic, even antipsychotic effects.
A failure to distinguish between the temporary reduction of inflammatory symptoms via immune system suppression and a genuinely anti-inflammatory effect of improvements in metabolic function makes it more likely that treatment methodologies for depression which end up being counter-productive in the long term continue to be popular.
These kinds of misconceptions add weight to flawed arguments claiming that sugar promotes inflammation and mood related issues and that fish oil is anti-inflammatory and a useful substance in the treatment of depression.
Exposure to continuously high levels of stress and interference with thyroid energy systems can increase activation of the sympathetic nervous system (suppressing digestion, impairing proper immune function and promoting mood destabilization) and some see depression as a kind of ‘allergy to modern life’.
Modern day stressors – including high intake of polyunsaturated fats, greater amounts of radiation and chemical toxins and poisons in the environment, social isolation, authoritarian school and workplace cultures – all have a part to play in relation to susceptibility to infection and inflammation and the the high cortisol high serotonin low energy states common to depression.
Rather than trying to pinpoint one cause, seeing how things that prevent optimal metabolic performance – including symptoms of suppressed metabolism – can be involved in disease promotion in general can make it possible for better approaches to healing to become available.
Looking at ways that chronic inflammation or infection cause depression will be far more worthwhile in the context of an appreciation of things that drive metabolism and protect against stress.
That way it should become more obvious that the treatment of one will usually also be part of the treatment of the others.
It’s a good idea to question whether things proposed for therapy are working in the same basic direction encouraging thyroid function and improving energy metabolism.
This way it doesn’t matter so much whether an infection caused the inflammation which lead to the depression or whether it was the result of some form of ongoing stress, because it will all be helpful information.
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