Depression: Overview

Depression is a serious yet common psychological condition that changes how and person thinks and feels, and also affects their social behavior and sense of physical well-being.

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We have all felt sad at one time or another, but that is not depression.  Sometimes we feel tired from working hard, or discouraged when faced with serious problems.  This too, is not depression.  These feelings usually pass within a few days or weeks, once we adjust to the stress.  If these feelings linger, intensify and begin to interfere with work, school or family responsibilities, then it may be depression.

3D image of the amygdala within the brain triggering emotion
Located deep within the brain, the amygdala processes important stimuli such as rewards and threats, and triggers emotions.

Some people have a chronic but less severe form of depression called dysthymia (or dysthymic disorder).  It is defined as a state of depressed mood that persists for at least two years and is accompanied by at least two other symptoms of depression.  These symptoms include poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions and feelings of hopelessness.

Approximately 2% of American adults have dysthymia in a given year.  Research has shown that stress in the form of loss, especially death of close family members or friends, may trigger major depression in vulnerable individuals.  While unipolar major depression and dysthymia are the primary forms of depression, a variety of other subtypes exist.

Incidence; Causes and Development

Close-up image of neurons firing within the amygdala
Brain circuits that normally regulate mood, such as those in the amygdala, become dysregulated in people with depression.

Each year over 6% of American adults experience a period of clinical depression.

As depression can have more than one cause, it is important to determine the primary or underlying cause whenever possible.

Signs and Symptoms

Depression, which can affect anyone, is often not recognized because many of the symptoms such as sleep and appetite disturbances mimic physical illness.

Diagnosis and Tests

A diagnosis of major depressive disorder is made if a person exhibits five or more of the main symptoms during a two-week period and impairment in normal functioning nearly every day during the same time.  Major depression often begins between the ages of 15 and 30 and episodes typically recur.

Treatment and Prevention

Once identified, most people diagnosed with depression can be successfully treated.  Too often, untreated or inadequately treated depression results in suicide or the destruction of family life.  The more serious the condition, the greater the importance of seeking medical and psychological help.

Natural medicine can play an important role in preventing or resolving depression.  Diet, supplementation, hormone replacement and balancing, allergy detection, herbs (such as the well documented use of St. Johns Wort) and other treatments have all been used successfully.

Signs, symptoms & indicators of Depression:

Supplements, Medications, Drugs

Symptoms - Aging


Symptoms - Environment

Poor reaction to cool damp weather

Bad weather can cause people to feel depressed or lethargic, both of which have been shown to worsen pain.

Symptoms - Food - General

Symptoms - Head - Mouth/Oral

(Much) reduced sense of taste

Depression is associated with reduced levels of serotonin and noradrenalin.  The decrease of these levels has been linked to the loss of sense of taste.

Symptoms - Mind - Emotional

(Very) angry/hostile disposition

Anger attacks occur in about two-thirds of those with depression.  People who have anger attacks typically have the most severe from of depression.

Being/being very easily irritated

A depressive person's irritability is often directed at those closest to them, namely as family and friends.  This alienating of loved ones and family disruption in itself can lead to higher risk of suicidal thoughts.


Symptoms - Mind - General

Symptoms - Reproductive - Female Cycle

Symptoms - Sleep

Frequent bizarre dreams

Studies have shown that people with depression can have three or four times the normal number of dreams.

Conditions that suggest Depression:


Poor Sense of Humor

Loss of one's appreciation of the rewarding aspects of humor is a frequent and fairly specific symptom of depression.


Problems Caused By Being Underweight

A major psychological cause of being underweight is depression.  Depressed individuals often have reduced appetite and rapid weight loss.


Rheumatoid Arthritis

Studies report that around 30% of people suffering from inflammatory diseases such as rheumatoid arthritis are depressed – more than four times higher than the general population.

Nervous System

Nervous Breakdown Tendency

There is always a trigger for a nervous breakdown, but underlying contributing factors such as depression are normally present.


Low Sex Drive

Mental states such as depression and strong emotions such as anger can effectively cool sexual desire.



Depression and hypersomnolence are often seen together.

Symptoms - Mind - General


Risk factors for Depression:


Parkinson's Disease

Depression is a common feature amongst Parkinson's disease victims.  Depression may be difficult to diagnose in patients with Parkinson's because the signs of these two disorders overlap.  In addition, patients with atypical Parkinson's more often have depression than patients with classical Parkinson's.


Allergic Tension Fatigue Syndrome

Various degrees of depression may exist in cases of Allergic Tension Fatigue Syndrome.



Megaloblastic Anemia / Pernicious Anemia

700 women over 65 (most in their mid-70s) in the Women's Health and Aging Study were interviewed and had blood samples taken for analysis.  Overall, 14% were mildly depressed and 17% were severely depressed.  Blood tests revealed that a deficiency in vitamin B12 was relatively common.  Of the severely depressed women, 27% were deficient in the vitamin, compared with only 17% of the mildly depressed women and 15% of their happier counterparts. [American Journal of Psychiatry 2000;157: pp.715-72]


Effects of a Low Carbohydrate Diet

The director of MIT's distinguished Clinical Research Center measured the serotonin levels in the brains of 100 volunteers eating different diets.  Serotonin is a chemical messenger in the human brain that regulates mood.  In fact, the way antidepressants like Prozac are purported to work is by increasing brain levels of serotonin.

What the MIT researchers found is that the brain only made serotonin after a person ate carbohydrates.  Carbohydrates seemed to naturally stimulate serotonin.  By starving of the brain of this essential mood elevator, the researchers fear that diets such as the Atkins Diet may make people restless, irritable or depressed.  Women, people under stress, and those taking anti-depressants may be most at risk. [MIT News 20 February 2004]

Yo-yo Dieting Consequences

Prolonged excessive calorie restriction can lead to depression and fatigue.


IBS (Irritable Bowel Syndrome)

October, 2013: Researchers from the Alimentary Pharmabiotic Centre at University College Cork reported that psychological factors such as anxiety and depression may be the central drivers of IBS, rather than the inflammation originating in the gut itself.  The most commonly-diagnosed psychiatric disorder in IBS patients is depression: one study reported that 38% of IBS patients had clinically-confirmed depression.  It is believed that IBS results from a complex interplay between psychological and biological factors.

Environment / Toxicity

Family History

Depression in family members

Research supports the existence of a genetic component toward developing depression.



Depression is a common symptom of hypothyroidism.


The Effects Of Overtraining

A 2016 study at the Technical University of Munich reported that young athletes who train excessively and don't leave enough time to recover from stress and injury have a 20% higher risk of suffering from depression due to changes in serotonin and tryptophan levels.


Low Serotonin Level

Serotonin levels can dictate if you feel depressed or not.  Antidepressant medications like Paxil, Zoloft, St. John's Wort, and Prozac work by preventing serotonin destruction and loss.  These antidepressants inhibit serotonin uptake (or reuptake) by the neurons in the brains.  Low serotonin levels cause depression.

Histadelia (Histamine High)

Histadelics are often chronically and suicidally depressed.

Estrogens Low

Low estrogen levels trigger the brain to release MAO, an enzyme in the brain which breaks down and destroys the neurotransmitter, serotonin.  Estrogen increases the destruction of this enzyme.  The lower your MAO enzyme levels the better you probably feel, since MAO breakdowns serotonin.  Low serotonin levels are associated with depression.

Low Male Testosterone Level

Depression can be caused by low levels of certain hormones, including testosterone.

Low Pregnenolone Level

A study found that depressed patients generally had low levels of pregnenolone. [Biological Psychiatry, 35(10): pp.775-80, 1994]


Chronic Fatigue / Fibromyalgia Syndrome

70% to 100% (different studies show various numbers) of fibromyalgia patients are found to have depression, though many consider that this is more likely to be a result of the muscular pain rather than part of the cause.

A sample of 69 patients with FM underwent a standardized tender point examination and a semistructured psychological interview and completed a set of self-report inventories.  Of the sample, 39 met criteria for depressive disorder and 30 did not. [Evaluation of the Relationship Between Depression and Fibromyalgia Syndrome: Why Aren't All Patients Depressed?  Akiko Okifuji, Dennis C. Turk, Jeffrey J. Sherman]


Lab Values

Elevated Homocysteine Levels

Nutrients which lower elevated homocysteine levels, including the B-vitamins, are related to depression in several ways [Am J Psy 1997;154: pp.426-428].  The methyl group provided by normal homocysteine metabolism is necessary for the production of depression-relieving neurotransmitters such as serotonin and dopamine.  The B-vitamins are also crucial in the direct synthesis of the brain neurotransmitters. [J Affect Disord. 1986;10: pp.9-13; Psychosomatics. 1980;21: pp.926-929]



Obsessive-Compulsive Disorder (OCD)

Depression is a common complication of OCD: "up to 80% of people diagnosed with obsessive compulsive disorder also suffer from depression" [Barlow, 1988].  This should not be surprising, given the distressing, time consuming, and interfering nature of obsessions and compulsions.


Many tinnitus sufferers become depressed simply from having to deal with the constant noise.  Treating the depression may make the tinnitus seem less severe.  Certain anti-depressants may worsen tinnitus, while others may improve it.  SRI anti-depressants may temporarily worsen tinnitus for the first few weeks.

Alprazolam (Xanax) in a double-blind study showed 76% of the subjects benefited with tinnitus reductions of at least 40%, whereas only 5% of the placebo subjects had an improvement. [Arch Otolaryngol Head Neck Surg. 1993:119: pp.842-5]



Endogenous depression – depression originating from within as opposed to being due to external factors – is a known symptom.

Problems Caused By Being Overweight

Obese and underweight persons are more often depressive than people in the normal body weight range.



Folic Acid Deficiency

There is substantial scientific evidence linking folic acid deficiency to depression.  Folate deficiency is common in depressed individuals. [Journal of Psychiatric Research 1982;20(2): pp.91-101, British Journal of Psychiatry 1991;159: pp.271-2, Nutrition Reviews 1997;55(5): pp.145-9]

Vitamin B-Complex Requirement

If you have very low levels of any of the B-vitamins, one of the first symptoms is depression.  Studies show that one out of four people hospitalized for depression is deficient in pyridoxine and cobalamin.

The B-vitamins are crucial in the direct synthesis of the brain neurotransmitters. [J Affect Disord. 1986;10: pp.9-13; Psychosomatics. 1980;21: pp.926-9]  Low levels of thiamin (B1) [Psychopharmacology (Berlin) 1997;129: pp.66-71], riboflavin (B2) and pyridoxine (B6) are often found in clinically depressed individuals. [British Journal of Psychiatry 1982;141: pp.271-2]

Manganese Requirement

Low blood manganese levels may accentuate depression.  A deficiency may contribute to depression stemming from low levels of the neurotransmitters serotonin and norepinephrine.

Vitamin B6 Requirement

B6 is a cofactor for the conversion of tryptophan to serotonin and for the synthesis of dopamine and norepinephrine.  It has been found to be quite low in patients admitted to hospital for depression. [Lancet April 18,1970, pp.832-33]  Some doctors claim that when women have depression and insomnia, B6 and tryptophan work consistently.

Vitamin B1 Requirement

See the link between Depression and B-complex Need.

Vitamin B2 Requirement

See the link between Depression and B-complex Need.

EFA (Essential Fatty Acid) Type 3 Requirement

Polyunsaturated omega-3 fatty acid deficiency may contribute to depressive symptoms in alcoholism, multiple sclerosis, postpartum depression and bipolar depression.  An insufficiency of omega-3 oils in the diet, especially the metabolite DHA, has been linked to depression.

Vitamin B12 Requirement

Studies show that one out of four people hospitalized for depression is deficient in pyridoxine and cobalamin.


Supplements, Medications, Drugs

Prednisone use

A side-effect of treatment with prednisone can be depression.

Symptoms - Muscular

Being very skinny

A study published in the American Journal Of Epidemiology reported that skinny men are 12% more likely to commit suicide than those of normal weight, while overweight men are 12% less likely to do so.  It may be that constantly 'feeling puny' has a demoralizing effect, or that their bodies produce insufficient amounts of serotonin (the 'feel-good' chemical), or the statistically proven fact that skinny men are more successful when they attempt suicide.  Drug overdoses are more likely to be fatal in those with a low BMI.

Being lean or underweight

Thin (but not too thin) people tend to feel physically good, and aren't forced to deal so much with social rejection, job discrimination, feeling unattractive, and other drawbacks of being overweight.  Having a healthy body and looking attractive also helps prevent depression.

Symptoms - Reproductive - General

(Several) past abortions

An analysis of research over 14 years involving 877,0000 women found that those who had an abortion were 37% more likely to experience Depression, 81% more likely to suffer from mental problems in general, and 155% more likely to commit suicide. [British Journal of Psychiatry, Volume 199, Issue 3, September 2011, pp.180-6]

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Depression suggests the following may be present:

Environment / Toxicity


Depression can lead to:


Coronary Disease / Heart Attack

While previous research has shown that depression in men and women is linked to heart disease, a recent study found that only men who are depressed face an increased risk of heart disease-related death. [Archives of Internal Medicine, May 8, 2000)]


Depression is emerging as a risk factor for heart disease.  A study of 688 women showed that depression and anger are associated with hardening of the arteries in women, in part through physical and behavioral risk factors such as bad cholesterol levels, obesity and smoking. [Psychosomatic Medicine, March/April 2001]



Excessive Fatigue

Depression robs the brain of some of the chemicals needed for optimal function.  Serotonin, for example, helps regulate the internal body clock.  Depression can lead to decreased energy levels and daytime tiredness, as well as difficulty falling asleep at night.  It can also cause us to wake up earlier in the morning than we had planned.

Recommendations for Depression:

Amino Acid / Protein


Particular precursors such as tyrosine, which increases dopamine and noradrenaline, show beneficial results in the treatment of mild depression.

Tryptophan / 5HTP

Tryptophan is a precursor to serotonin, a neurotransmitter that is frequently imbalanced in cases of depression.  Conventional antidepressants work to increase neurotransmitter levels by blocking their breakdown.  Depression associated with menstrual cycles and postpartum depression sometimes respond very well to tryptophan supplementation.  Postpartum women usually have high estrogen levels and it has been found that high estrogen levels increase the conversion of tryptophan to niacinProgesterone and hydrocortisone decrease its conversion.  Women on birth control pills, when given vitamin B6 and tryptophan, generally tend to metabolize tryptophan more normally.


Phenylalanine can affect depression via three separate pathways.

  1. D-phenylalanine (DPA) exerts antidepressant activity due to its metabolism to phenylethylamine (PEA).
  2. DPA inhibits the breakdown of the body's endogenous opiates thus producing a state of euphoria.
  3. Phenylalanine is an important precursor for the production of noradrenaline and adrenaline thus increasing the body's ability to cope with stress.

A number of double-blind clinical trials have demonstrated that dosages of DLPA, the form commonly found in supplements, at doses as low as 150mg per day is effective in the treatment of some forms of depression.

Botanical / Herbal

St John's Wort

St. John's Wort has been shown to have a 60% to 70% response rate in adult patients with mild-to-moderate depression.  A 2001 study found St. John's Wort (300mg extract per day) effective in children with mild to moderate depression also.  Ratings of "good" or "excellent" were found by physicians to be 72% after 2 weeks, 97% after 4 weeks and 100% after 6 weeks.  The ratings by parents were 65% after 2 weeks, 93% after 4 weeks and 98% at 6 weeks.  The medication was tolerated well. [Phytother. Res 2001; 15: pp.367-70]

A large trial compared St. John's wort extract with sertraline (Zoloft) and a placebo in adults with depression.  The trial found that neither St. John's wort nor sertraline were more effective than placebo in treating major depression.  Most successful trials with St. John's wort have focused on persons with milder forms of depression.  St. John's wort should be used primarily for mild to moderate depression as well as dysthymia. [JAMA 2002;287: pp.1807-14]


High/Increased Carbohydrate Diet

A carbohydrate-rich diet helps the body produce serotonin – the "happy" hormone.  Special serotonin foods include oats, whole-wheat products, bananas and other carbohydrate-rich foods.

Aspartame (Nutrasweet) Avoidance

A double blind study on the effects of aspartame on persons with mood disorders was conducted by Dr. Ralph G. Walton.  The study showed a large increase in serious symptoms for persons taking aspartame.  Since some of the symptoms were so serious, the Institutional Review Board had to stop the study.  Three of the participants had said that they had been "poisoned" by aspartame.  Dr. Walton concluded that "individuals with mood disorders are particularly sensitive to this artificial sweetener; its use in this population should be discouraged." [Biol Psychiatry. 1993 Jul 1-15;34(1-2): pp.13-7]

Since the study wasn't funded/controlled by the makers of aspartame, The Nutrasweet Company refused to sell him the aspartame.  Walton was forced to obtain and certify it from an outside source.

Aware that the experiment could not be repeated because of the danger to the test subjects, Walton was quoted as saying, "I know it causes seizures.  I'm convinced also that it definitely causes behavioral changes.  I'm very angry that this substance is on the market.  I personally question the reliability and validity of any studies funded by the Nutrasweet Company."

There are numerous reported cases of low brain serotonin levels, depression and other emotional disorders that have been linked to aspartame and often are relieved by stopping the intake of aspartame.  Researchers have pointed out that increases in phenylalanine levels in the brain leads to a decreased level of the neurotransmitter serotonin, which leads to a variety of emotional disorders.  Dr William M. Pardridge of UCLA testified before the US Senate that a youth drinking four 16-ounce bottles of diet soda per day would lead to an enormous increase in phenylalanine levels.


Aerobic Exercise

Researchers found that walking for 30 minutes each day quickly improved depressive symptoms faster than antidepressant drugs typically do.  Another study compared exercise with antidepressants among older adults and found that physical activity was the more effective depression-fighter. [British Journal of Sports Medicine April 2001;35: pp.114-7]

Previous studies have suggested that exercise is a potent mood-booster, and some research indicates that for some patients regular activity may be a better depression treatment than psychotherapy or medication.  Exactly why is unclear, but exercise does influence certain mood-related hormones.  And it is also believed to enhance people's sense of control over their lives.

The main conclusion to draw from studies conducted is that the practice of exercise shows a negative correlation with depression – in other words, the more you exercise, the less depressed you feel.  Interestingly, any kind of exercise relieves the symptoms of depression.



DHEA is a plentiful adrenal steroid hormone whose quantity decreases with age and may have significant psychiatric effects.  In one study, six middle-aged and elderly patients with major depression and low plasma DHEA or DHEA-S levels were openly administered DHEA (30-90mg per day for 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals.  Depression ratings as well as aspects of memory performance significantly improved.

One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%.  These measures returned to baseline after treatment ended.  Improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. [Biol Psychiatry, 1997 Feb; 41:3, pp.311-8]

Another study evaluated the efficacy of very high doses of DHEA (450mg) in the treatment of midlife-onset dysthymia.  In 15 patients who completed the study, a robust effect of DHEA on mood was observed compared with placebos.  60% of the patients responded to DHEA at the end of the 6-week treatment period compared with 20% on placebo.  A significant response was seen after 3 weeks of treatment on 90mg per day.  The symptoms that improved most significantly were anhedonia (failure to experience pleasure), loss of energy, lack of motivation, emotional "numbness", sadness, inability to cope, and worry. [Biol Psychiatry 1999 Jun 15; 45(12): pp.1533-41]

In a study conducted by S. S. C. Yen and associates at the University of California, San Diego, researchers found that 50mg a day of DHEA administered for 6-months restored levels of DHEA in both men and women.  This DHEA replacement was associated with an increase in perceived physical and psychological well-being for both men (67%) and women (84%).

Another study at UCSD was conducted in which researchers considered the association between levels of DHEA and depression.  Nine different hormones (including DHEA) were measured in 699 older women.  Out of all of these hormones, only low levels of DHEA were linked with depression.

In studies conducted at Cambridge University in England, researchers discovered that children with major depression have abnormally low levels of DHEA accompanied by abnormally high levels of cortisol.

University of California San Francisco At the University of California, San Francisco, DHEA was given to people with depression to determine its antidepressant effects.  After 6 weeks, psychological tests indicated that about half the participants responded to DHEA therapy, with an overall enhancement of mood scores by over 30%.

In another study conducted by the Department of Psychiatry at UCSF, DHEA was administered to six middle-aged and elderly patients with major depression.  In patients who received extended treatment with DHEA for six months, depression ratings improved 48-72%.

In a study conducted by researchers at the National Institute of Mental Health, middle-aged people with dysthymia (a chronic, low-grade depression) were given 90mg of DHEA a day for 3 weeks.  This study concluded that this amount significantly alleviated the participants' depression.

DHEA is the only hormone besides cortisol and serotonin that has consistently been linked to depression.  But unlike cortisol, where high levels increase depression, high levels of DHEA actually alleviate depression.

Researchers have different theories about how DHEA alleviates depression.  DHEA and can cross the blood-brain barrier and interact with the brain directly.  DHEA can affect serotonin, GABA receptors, and other brain factors.  It might modulate the serotonin-signaling pathway.  In addition, DHEA is the precursor for estrogen and testosterone, which also enhance mood.

DHEA also has antistress effects that may be part of its antidepressant action.  Research shows that cortisol, the stress hormone, is elevated in cases of major depression.  DHEA counteracts cortisol.  Calmness is also associated with higher levels of DHEA.

Not recommended

On the basis of theoretical ideas about how melatonin works, some authorities specifically recommend against using it for depression, schizophrenia, autoimmune diseases and other serious illnesses, and in pregnant or nursing women.

Some studies showing melatonin to be an effective treatment for depression were flawed.  Melatonin is unlikely to produce significant positive effects in the treatment of depression in most patients, especially if the patient is not already melatonin-deficient.  Badly timed use of melatonin can worsen depression.  However, some patients with SAD (seasonal affective disorder, a form of depression associated with the shortening of the days in autumn and winter) have been shown to have disrupted melatonin cycles, and have been treated effectively with light therapy.

Laboratory Testing

Amino Acid Profile

Amino acid profiles done on blood can reveal imbalances seen in a variety of disorders including depression.  Low tyrosine or phenylalanine levels can result in abnormal levels of mood-regulating chemicals in the brain, such as dopamine and catecholamines.  Low tyrosine levels can also create subnormal levels of thyroid hormone – a well-known cause of depression.

Methionine is the precursor of SAMe which is needed for proper functioning of catecholamines and may be low in patients with depression.

Tryptophan is the body's source material for producing the hormones serotonin and melatonin, which also influence sleep patterns and mood.  Depletion of tryptophan can cause an increase in depressed mood states; lower tryptophan levels have been correlated with a higher depression score even in patients who were already under treatment with anti-depressant drugs. [Arch Gen Psychiatry 1990;47(5): pp.411-18]



Because of its nerve and muscle support, magnesium may also be helpful for depression.

Physical Medicine

Calming / Stretching Exercises

A few studies have looked at the effects of yoga breathing exercises – practiced daily for several weeks – on depression.  One study showed that breathing exercises produced faster improvement than no treatment.  Another study found that breathing exercises were as effective as an antidepressant drug for patients who were severely depressed, but less effective than electroconvulsive therapy (ECT).



During milder episodes of depression, it is good to reach out to others – talk to someone you trust.  Sometimes, especially when people experiencing more severe depression and struggling just to get through the days, they need the help of a professional.  Counseling and psychotherapy are extremely effective in treating depression, either alone or in conjunction with medication.  The important thing to know is that depression is one of the most well-understood and treatable psychological disorders, and help is available.  Certain types of psychotherapy, namely cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT), have been shown to be particularly effective.


EPA (eicosapentanoic acid)

There is an increasing body of evidence that indicates that fish oils, in particular those with high EPA to DHA ratios, have a major role to play in helping people maintain good mental health and to avoid mood swings and mild depression.  Currently the only available source of EPA without equal amounts of DHA being present is "EPA rich" fish oil.


DMAE reduces apathy and increases motivation in persons afflicted with depression.

TMG (Trimethylglycine)

The compound 5-adenosylmethionine (SAMe), potentially produced through the demethylation of TMG, has been shown to alleviate depression.


Vitamin B-Complex

A combination of vitamins B6, B9 (folic acid) and B12 improves mood.  These nutrients play an indirect but critical role in the formation of serotonin and other neurotransmitters, and deficiencies – which are linked to high levels of homocysteine – are linked with mood disorders.  Although B-complex vitamins are not a stand-alone treatment for depression, they're an important adjunct.

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