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10 Triggers of inflammation to be avoided, to reduce the risk of depression

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According to the World Health Organization, depression is one of the most prevalent serious brain disorders and the No. 1 cause of dis­ability in the world. Preventing or reducing the incidence and preva­lence of depression is therefore a major public health priority.



Neuroinflammation is well-established as an underlying mechanism in depres­sion, as well as in other neuropsychiat­ric disorders, including schizophrenia, multiple sclerosis, stroke, Parkinson’s disease, and sleep disorders.1 There is a dearth of prevention strategies for neuropsychiatric disorders but, given emerging scientific knowledge about immune dysregulation and the asso­ciated rise in inflammatory markers during the course of depression,2,3 it is logical to postulate that avoiding trig­gers of neuroinflammation might be a useful tactic to prevent depression or, perhaps, to minimize its severity.

Challenge your patients to avoid triggers of depression
What is known about what instigates the rise of inflammatory markers in the body and the brain? Actually, quite a substantial body of knowl­edge exists on the subject.4 Consider the 10 risk factors for depression that I enumerate here (Table), and advise patients to avoid them.

Sedentary lifestyle. Physical inac­tivity during childhood is associated with depression in adulthood. This is worrisome because video games seem ever more popular among children these days—more popular and preva­lent than playing outdoors. Use this knowledge about the preventive ben­efit of exercise for long-range preven­tion in young patients.

Adults with a sedentary lifestyle usually have increased adiposity, which increases the risk of depres­sion. Regular exercise has been shown to down-regulate systemic inflammation.

Smoking. Hundreds of toxic and inflammatory components in tobacco smoke (tars, metals, free radicals) can induce inflammation across the body and brain tissue, which explains not only depression but serious pulmo­nary and cerebrovascular diseases seen in smokers. People with depres­sion are more likely to smoke than the general population, possibly because nicotine has a mild mood-elevating effect. Yet smoking might make depression worse by exacerbat­ing inflammation, thus negating any mood-elevating effect of nicotine.

Poor diet. It is well known that the Western diet (processed meats, refined sugars, saturated fats) can increase the body’s level of inflammatory mark­ers. The Mediterranean diet, on the other hand, which comprises fruits, vegetables, fish, legumes, and foods rich in omega-3 fatty acids (fish, nuts, leafy green vegetables), is anti-inflammatory. Furthermore, lycopene-containing foods (tomatoes, papaya, red cabbage, watermelon, carrots, asparagus) are rich in antioxidants and thus reduce inflammation.

The possible epigenetic effects of diet are an interesting phenomenon. Offspring of rats who were fed a diet rich in saturated fats have elevated levels of inflammatory markers, even when they had been fed a normal diet, suggesting a transgenerational effect. What parents eat before they conceive might doom their child’s health— regardless of what they feed them.

Tooth decay, gingivitis, periodon­titis. Oral inflammation afflicts a large percentage of the population. These conditions can lead to sys­temic inflammation with elevated levels of C-reactive protein (CRP) and interleukins, which are conducive to depression.

Poor sleep hygiene. Sleep disorders, such as insomnia and insufficient sleep (which is epidemic in the United States), are risk factors for mood dis­orders. Sleep deprivation disrupts immune function and triggers the cascade of elevated cytokines, CRP, and tumor necrosis factor (TNF)-α. Just as depression is associated with impaired neurogenesis, so is chronic lack of sleep, suggesting a conver­gence of neurobiologic mechanisms.

Vitamin D deficiency. A link between vitamin D deficiency, now common in the United States, and depression and immune function has been recognized. Vitamin D has anti-inflammatory effects and can reduce oxidative stress, which culminates in inflammation. Vitamin D supple­mentation has been shown to allevi­ate neuro-immune disorders, such as multiple sclerosis.

Obesity. Obese people are >50% more likely to develop depression than non-obese people. Technically, obesity is a pro-inflammatory state, and inflam­matory biomarkers, such as cytokines, are abundant in fat cells, especially abdominal (visceral or peri-omental) adiposity. When an obese person loses weight, levels of inflammatory markers (interleukin-6, TNF-α, leptin) decrease. We know that abdominal obesity is associated with neuroin­flammation and early dementia.

Allergy involves inflammation trig­gered by the cascade of events con­sequent to the body’s fight against antigens, and the well-known hyper-sensitivity reaction, causing edema, coughing, sneezing, and itching. It is well-established that the incidence of atopy and allergy is high among peo­ple with depression.

Changes in gut permeability. Intestinal inflammatory diseases, such as ulcerative colitis, are recog­nized as pathways to depression. The mechanism is believed to be the immune response to lipopolysaccha­rides by commensal bacteria that live by the trillions in the gut. The result? Abnormal gut permeability, bacterial translocation, and depressed mood, possibly because serotonin is more abundant in the gut than in the CNS.

Stress. Arguably, the most common pathway to depression is stressful events of daily life. Stress-induced systemic inflammation hastens cardio­vascular disease and leads to neuro-inflammation and neuropsychiatric disorders as well.

Especially malignant is the severe stress of childhood trauma (physi­cal and sexual abuse, parental dis­cord and death), which stimulates pro-inflammatory cytokines and detrimental neurobiological sensiti­zation that lead to psychopathology, including depression and psychosis in adulthood. Childhood trauma has been reported to shorten life by 7 to 15 years.


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