Chronic Stress, agitation, fatigue, despair, guilt, insomnia, apathy

Natural Herbal Help for Depression, Chronic Stress, and Mood or Psychological Disorders

Considered a severe neurological disorder, experts estimate that between 15-20% of people worldwide suffer from depression. Conventional antidepressant drugs are ineffective in up to 30% of patients. Could turmeric compounds help? Some research suggests that they can-especially curcumin. (iv.124)

Chronic stress—psychological, social, and physical—is now understood to play an important role in neurological damage. This can cause and exacerbates depression, anxiety, and other mood or psychological disorders. Because of this, many antidepressants also alleviate the effects of chronic stress. Some of these include memory loss and cognitive deficits. Unfortunately, some antidepressants also have adverse side effects. (iv.28124)

Turmeric compounds are also known to have anti-stress properties. Natural herbal remedies made with turmeric may provide safe and effective relief for some people diagnosed with stress and mood disorders, including depression. (iv.28124)

What are the Symptoms and Causes of Major Depression?

Some of the symptoms associated with major depressive disorder include: (iv.7124)

  • Agitation
  • Fatigue
  • Feelings of despair and guilt
  • Inability to concentrate
  • Inability to learn
  • Insomnia or excessive sleep
  • Irritable mood
  • Lack of interest in enjoyable activities
  • Memory loss
Figure IV.21: Mood Disorders and Inflammation

Figure IV.21: Mood Disorders and Inflammation

What Does Inflammation Have to Do With Mood Disorders?

Medical research has determined that chronic inflammation is a primary contributing factor to the development and progression of psychiatric illness, including major depression. The latter was a somewhat confusing discovery since inflammation is typically associated with a heightened immune system response and higher levels of immune system cells. However, people with depression usually have lower levels of lymphocyte and natural killer immune system cells. (iv.28)

Despite the seemingly reduced immune system response, blood tests showed increased production of inflammatory cytokines in these patients. In fact, higher levels of cytokines are linked to more severe symptoms in depression. One explanation for the conflicting evidence could be that the immune system's T-cells are dysregulated and promote inflammatory cytokines. For example, this could occur when less T-reg cells that produce anti-inflammatory cytokines are produced and more T-eff cells that stimulate inflammatory IL-17 cytokines are secreted. (iv.28)

Research indicates that many physical health conditions, chronic stress, interferon-α (IFN-α) treatment for cancer or hepatitis C, and lifestyle factors (e.g., diet and social environment) cause inflammatory activity in the brain. All of these affect a number of areas that regulate mood. These stressors stimulate inflammatory proteins in the brain and activate microglia cells, which are the brain's version of immune system's macrophage cells: (iv.2830)

Once activated, a destructive, cascading cycle of inflammatory cytokine proteins and free radical damage to mitochondria in brain cells occurs. This cell damage translates into a number of different mood disorders: (iv.2830)

Table IV.8: Mood Disorders and Specific Inflammatory Effects in Brain
MOOD DISORDER INFLAMMATORY SYMPTOMS IN BRAIN

Bipolar Behavior

Depression

Schizophrenia

Excitotoxicity: The brains of suicide victims with depression, bipolar disorders, and schizophrenia show evidence of chronic inflammation. This includes over-excited brain cells and increased microglial density.

Depression

High levels of chronic inflammatory markers: Obesity and stress correspond to increased levels of pro-inflammatory cytokine proteins IL-6, hs-CRP, and IL-1ra as well as inflammatory COX enzymes. All correlate with increased occurrence of mood disorders such as depression.

Reduced production of neurotransmitters related to mood: Increases in the cytokine protein IL-6 in cerebrospinal fluid appears to inhibit serotonin. This is an important neurotransmitter for regulating mood. Studies indicate inflammatory cytokine proteins, transcription factors, and kinase proteins stimulate an enzyme that breaks down the tryptophan precursor to serotonin.

The metabolites from the breakdown of serotonin reduce levels of other important neurotransmitters that can affect mood. Specifically, these metabolites can inhibit production of glutamate and dopamine.

This could explain why IFN-α treatment for hepatitis and melanoma are also associated with reduced dopamine levels. Since IFN-α stimulates cytokines such as IL-6, it could promote the enzyme that breaks down serotonin and block dopamine production.

Depression

Loneliness

Increased cortisol and corticotrophin-releasing hormone concentrations: Higher levels of inflammatory transcription factor NF-κB activity and reduced glucocorticoid receptors can increase levels of cortisol and related hormones. In turn, this can also increase resistance to glucocorticoid anti-inflammatory treatments.

Anxiety

Depression

Neurotic Behavior

Obsessive-Compulsive Behavior

Activated dACC region in brain cortex: Psychosocial stressors activate dACC and increase levels. The causes greater sensitivity to any other stimuli and contributes to anxiety.

Depression

Exposure to toxins that damage neurons: Animal studies show that toxins increase levels of the inflammatory protein TNF-α;. The related free radical stress damages or destroys dopamine-producing neuron brain cells and reduces levels of the neurotransmitter dopamine (associated with depressive symptoms).

How Can Turmeric Help?

Turmeric compounds have antioxidant and anti-inflammatory properties that could counteract or prevent some of the underlying chemical imbalances in mood disorders. Studies suggest that COX-2 inflammatory enzyme inhibitors such as curcumin could reduce symptoms and even bring about remission in some patients with depression. COX-2 inhibitors even appear to benefit those patients who are non-responsive to conventional antidepressant medication. (iv.28)

In other studies, substances that inhibit the inflammatory transcription factor and kinase proteins p38 and MAPK had antidepressant effects. Curcumin is known to inhibit these inflammatory proteins. Blocking them also helps prevent opioid tolerance. Researchers suggest that natural substances such as curcumin from turmeric that inhibit NF-κB and block excitotoxicity could also be beneficial in treating mood disorders. (iv.28)

Lab and animal experiments demonstrate that curcumin has these properties and others that could help prevent or relieve the symptoms of depression and other mood disorders:

Table IV.9: Curcumin Beneficial Effects in Anxiety and Depression
CONDITION CURCUMIN EFFECTS

Corticosterone-induced depression (iv.27)

  • Significantly reversed depressed behavior.
  • BDNF, a protein that boosts growth and viability of brain cells.
  • Reversed lower levels of serotonin-related receptors.
  • Protected neurons from cell changes or death due to corticosterone.

Depression induced by chronic stress (iv.8)

  • Brain cells.
  • Receptors for serotonin, a mood-related neurotransmitter.

Depression (iv.3)

  • Monoamine oxidase (MAO), an enzyme that breaks down neurotransmitters.
  • Levels of serotonin and dopamine remaining in the brain. This is similar to how conventional MAOI antidepressants work.

Arsenic induced depression (iv.7)

  • Restored normal serotonin levels.
  • Oxidative free radical stress.

Stress-induced depression (iv.7)

Stress-induced depression (iv.7)

Chronic, unpredictable stress-induced abnormal behavior and depression (iv.7)

  • Relieved or reversed neuron growth-suppressing effects of stress in the hippocampus at doses between 5-20 mg/kg of body weight (bw). Results were similar to 10 mg/kg-bw doses of the conventional antidepressant drug imipramine.
  • Prevented stress-induced BDNF levels.

Anxiety induced by stress (iv.17)

  • 20 mg/kg bw doses of curcumin significantly reduced anxiety symptoms.
  • Free radicals levels.

Anxiety-like behavior induced by sleep deprivation (iv.18)

  • 10 and 20 mg/kg bw doses of curcumin for 5 days significantly prevented negative side effects of 72 hours of sleep deprivation. Some of the effects of sleep deprivation include anxious behavior, impaired movement, and weight loss.
  • Antioxidant levels.
  • Free radicals levels.

Clinical Studies for Depression

Clinical evidence for turmeric compounds in treating depression is limited, but generally positive. In one study, adding curcumin to antidepressant treatment did not appear to improve their effectiveness. The 5 week study involved 40 patients. Twenty of the patients were treated with an antidepressant drug combined with 500 mg of curcumin a day, and 20 were given the antidepressant with a placebo. Symptoms improved in all patients after a week but there were no significant difference between the placebo and curcumin groups. The researchers did note that the curcumin group showed a positive trend toward more rapid relief of symptoms. (iv.175)

Results from two more recent randomized clinical trials showed positive evidence of the antidepressant effects of turmeric compounds:

In a 6 week blinded study, patients were given 1 of 3 different treatments: 1000 mg/day of curcumin/turmeric oil, 20 mg/day of fluoxetine, or a combination of the two (20 patients in each group). Curcumin was as effective as fluoxetine, using the Hamilton Depression Rating Scale. The combination treatment showed a slightly better response rate, but it was not statistically significant. (iv.176)

In an 8 week double-blinded, placebo controlled clinical trial, 56 patients were randomly assigned to take either 1000 mg/day of curcumin or a placebo (28 in each group). Almost all of the participants finished the study (25 in the curcumin group, and 27 in the placebo group). Baseline differences in depression scores were negligible between the two groups. In both groups, the test scores for both depression and anxiety improved for the first 4 weeks. However, after that improvements in both anxiety and depression symptoms continued only in the group taking curcumin. (iv.177)

These studies are promising, given the risk of negative side effects (such as increased suicidal thoughts or actions, insomnia, and anxiety) from pharmaceutical antidepressants. Turmeric compounds have none of these potential side effects. (iv.178-182)

Other Beneficial Turmeric Compounds to Boost Mood

Other turmeric compounds may also help prevent or relieve the symptoms of mood disorders. Studies show they are able cross the brain-blood barrier in order to benefit neuron brain cells. (iv.1034, 38-39, 125)

These include:

Table IV.10: Turmeric Compounds That Help Make You Feel Better
TURMERIC COMPOUND EFFECT

CINNAMIC ACID

  • Neuroprotective. (iv.76)
  • Experts suggest it is highly likely to have antidepressant properties. (iv.66)

EUGENOL

  • Inhibits overexcited, inflammatory conditions in brain that promote damage to neuron brain cells. (iv.126)
  • Stimulates BDNF growth factor, which promotes neuron health and growth. (iv.3)
  • May increase dopamine levels. (iv.110)
  • Has properties that reduce anxiety. (iv.126)

FARNESOL

  • Calming and anti-anxiety effects. (iv.127)

FOLATE

  • Improves effectiveness of antidepressant drugs. (iv.28)

LIMONENE

  • Animal studies show limonene has anti-anxiety properties. (iv.126)

NIACIN

  • Essential nutrient for cell energy(iv.39)
  • Needed to make neurotransmitters (chemicals in the brain associated with mood and brain function). (iv.39)

QUERCETIN

  • Inhibits enzymes that can cause free radical damage and inflammatory conditions in the brain which can lead to neurological and mood disorders. (iv.3269128)
  • Quercetin has antidepressant properties. These may be associated with increased BDNF growth and CREB transcription factor levels. In the brain, both promote neuron health and survival. (iv.129)
  • In animal studies, reduces symptoms of anxiety. (iv.130)
  • Quercetin may increase bioavailability of curcumin in the brain. (iv.77)

THIAMINE

  • Thiamine is a necessary B vitamin for brain cell health. (iv.4270)
  • Thiamine deficiency can cause confusion and depression. (iv.4270)
IL-10 and TGF-β. (iv.28)
For example, insufficient magnesium in the diet causes deficiency that impacts neuron brain cell health. (iv.30)
Specifically, IL-6. (iv.2830)
An inflammatory transcription factor. (iv.28)
By increasing cytokine PKA and transcription factor CREB activity. (iv.27)
Specifically, nitric oxide (NOS) type of free radicals. (iv.17)
Specifically, glutathione. (iv.18)
Specifically, tyrosinase, LOX, COX-2, and PLA2. (iv.3269128)
Vitamin B9, also known as folic acid. (iv.39)
Vitamin B3; supports mitochondria and cell energy production as well. (iv.39)
Either escitalopram (Lexapro®) or venlafaxine (Effexor®). (iv.175178-179)
Prozac®. (iv.180)
BCM-95®, containing 88% curcuminoids and 7% turmeric oil. (iv.176)
Using the Inventory of Depressive Symptomatology self-rated version (IDS-SR30). (iv.177)
Using the Spielberger State-Trait Anxiety Inventory (STAI) test. (iv.177)

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