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Nutritional therapies for mental disorders

Shaheen E Lakhan* and Karen F Vieira

Author Affiliations

Global Neuroscience Initiative Foundation, Los Angeles, CA, USA

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Nutrition Journal 2008, 7:2  doi:10.1186/1475-2891-7-2

The electronic version of this article is the complete one and can be found online at:

Received:28 July 2007
Accepted:21 January 2008
Published:21 January 2008

© 2008 Lakhan and Vieira; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD).

Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained.


Currently, approximately 1 in 4 adult Americans have been diagnosed with a mental disorder, which translates into about 58 million affected people [1]. Though the incidence of mental disorders is higher in America than in other countries, a World Health Organization study of 14 countries reported a worldwide prevalence of mental disorders between 4.3 percent and 26.4 percent [2]. In addition, mental disorders are among the leading causes for disability in the US as well as other countries. Common mental health disorders include mood disorders, anxiety disorders such as post-traumatic stress disorder (PTSD), panic disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), and autism. However, the four most common mental disorders that cause disabilities are major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) [3,4].

Typically, most of these disorders are treated with prescription drugs, but many of these prescribed drugs cause unwanted side effects. For example, lithium is usually prescribed for bipolar disorder, but the high-doses of lithium that are normally prescribed causes side effects that include: a dulled personality, reduced emotions, memory loss, tremors, or weight gain [5,6]. These side effects can be so severe and unpleasant that many patients become noncompliant and, in cases of severe drug toxicity, the situation can become life threatening.

Researchers have observed that the prevalence of mental health disorders has increased in developed countries in correlation with the deterioration of the Western diet [7]. Previous research has shown nutritional deficiencies that correlate with some mental disorders [8,9]. The most common nutritional deficiencies seen in mental disorder patients are of omega-3 fatty acids, B vitamins, minerals, and amino acids that are precursors to neurotransmitters [10-16]. Compelling population studies link high fish consumption to a low incidence of mental disorders; this lower incidence rate has proven to be a direct result of omega-3 fatty acid intake [10,17,18]. One to two grams of omega-3 fatty acids taken daily is the generally accepted dose for healthy individuals, but for patients with mental disorders, up to 9.6 g has been shown to be safe and efficacious [19-21]. Western diets are usually also lacking in fruits and vegetables, which further contributes to vitamin and mineral deficiencies.

This article will focus on the nutritional deficiencies that are associated with mental disorders and will outline how dietary supplements can be implemented in the treatment of several disorders (see Table 1 for an overview). The mental disorders and treatments covered in this review do not include the broad and complex range of disorders, but however focuses on the four most common disorders in order to emphasize the alternative or complementary nutritional options that health care providers can recommend to their patients.

Table 1. Summary of proposed causes and treatments for common mental health disorders

Major Depression

Major depression is a disorder that presents with symptoms such as decreased mood, increased sadness and anxiety, a loss of appetite, and a loss of interest in pleasurable activities, to name a few [22]. If this disorder is not properly treated it can become disabling or fatal. Patients who are suffering from major depression have a high risk for committing suicide so they are usually treated with psychotherapy and/or antidepressants [23]. Depression has for some time now been known to be associated with deficiencies in neurotransmitters such as serotonin, dopamine, noradrenaline, and GABA [22-27]. As reported in several studies, the amino acids tryptophan, tyrosine, phenylalanine, and methionine are often helpful in treating many mood disorders, including depression [28-33]. Tryptophan is a precursor to serotonin and is usually converted to serotonin when taken alone on an empty stomach. Therefore, tryptophan can induce sleep and tranquility and in cases of serotonin deficiencies, restore serotonin levels leading to diminished depression [15,31].

Tyrosine is not an essential amino acid, because it can be made from the amino acid phenylalanine. Tyrosine and sometimes its precursor phenylalanine are converted into dopamine and norepinephrine [34]. Dietary supplements that contain tyrosine and/or phenylalanine lead to alertness and arousal. Methionine combines with ATP to produce S-adenosylmethionine (SAM), which facilitates the production of neurotransmitters in the brain [35-38]. Currently, more studies involving these neurochemicals are needed which exhibit the daily supplemental doses that should be consumed in order to achieve antidepressant effects.

Since the consumption of omega-3 fatty acids from fish and other sources has declined in most populations, the incidence of major depression has increased [10]. Several mechanisms of action may explain how eicosapentaenoic acid (EPA) which the body converts into docosahexaenoic acid (DHA), the two omega-3 fatty acids found in fish oil, elicit antidepressant effects in humans. Most of the proposed mechanisms involve neurotransmitters and, of course, some have more supporting data than others. For example, antidepressant effects may be due to EPA being converted into prostaglandins, leukotrienes, and other chemicals the brain needs. Other theories state that EPA and DHA affect signal transduction in brain cells by activating peroxisomal proliferator-activated receptors (PPARs), inhibiting G-proteins and protein kinase C, as well as calcium, sodium, and potassium ion channels. No matter which mechanism(s) prove to be true, epidemiological data and clinical studies already show that omega-3 fatty acids can effectively treat depression [39]. Consuming omega-3 fatty acid dietary supplements that contain 1.5 to 2 g of EPA per day have been shown to stimulate mood elevation in depressed patients. However, doses of omega-3 higher than 3 g do not present better effects than placebos and may not be suitable for some patients, such as those taking anti-clotting drugs [40].

In addition to omega-3 fatty acids, vitamin B (e.g., folate), and magnesium deficiencies have been linked to depression [9,13,14]. Randomized, controlled trials that involve folate and B12 suggest that patients treated with 0.8 mg of folic acid/day or 0.4 mg of vitamin B12/day will exhibit decreased depression symptoms [9]. In addition, the results of several case studies where patients were treated with 125 to 300 mg of magnesium (as glycinate or taurinate) with each meal and at bedtime led to rapid recovery from major depression in less than seven days for most of the patients [14].

Bipolar Disorder

A patient suffering from major depression may also present symptoms such as recurring episodes of debilitating depression, uncontrollable mania, hypomania, or a mixed state (a manic and depressive episode) which is clinically diagnosed as bipolar disorder [41]. Some biochemical abnormalities in people with bipolar disorder include oversensitivity to acetylcholine, excess vanadium, vitamin B deficiencies, a taurine deficiency, anemia, omega-3 fatty acid deficiencies, and vitamin C deficiency.

Bipolar patients tend to have excess acetylcholine receptors, which is a major cause of depression and mania [42,43]. Bipolar patients also produce elevated levels of vanadium, which causes mania, depression, and melancholy [44,45]. However, vitamin C has been shown to protect the body from the damage caused by excess vanadium. A double-blind, placebo controlled study that involved controlling elevated vanadium levels showed that a single 3 g dose of vitamin C decreases manic symptoms in comparison to placebo [45].

Taurine is an amino acid made in the liver from cysteine that is known to play a role in the brain by eliciting a calming effect. A deficiency of this amino acid may increase a bipolar patient's manic episodes. In addition, eighty percent of bipolar sufferers have some vitamin B deficiencies (often accompanied by anemia) [46]. The combination of essential vitamin supplements with the body's natural supply of lithium reduces depressive and manic symptoms of patients suffering from bipolar disorder [47].

Another well-known factor for mental disorders is that cells within the brain require omega-3 oils in order to be able to transmit signals that enable proper thinking, moods, and emotions. However, omega-3 oils are often present at very low levels in most Americans and bipolar sufferers [48]. Numerous clinical trials, including double-blind, placebo controlled studies have been performed which show that 1 to 2 grams of omega-3 fatty acids in the form of EPA added to one's daily intake decreases manic/depressive symptoms better than placebo (See Table 1).

Prescription lithium is in the form of lithium carbonate, and doses can be as high as 180 mg. It is these high doses that are responsible for most of lithium's adverse side effects. Some of the more common side effects include a dulled personality, reduced emotions, memory loss, tremors, or weight gain [5,6]. Another form of lithium called lithium orotate, is preferred because the orotate ion crosses the blood-brain barrier more easily than the carbonate ion of lithium carbonate. Therefore, lithium orotate can be used in much lower doses (e.g. 5 mg) with remarkable results and no side effects [49,50]. Clinical trials involving 150 mg daily doses of lithium orotate administered 4 to 5 times a week, showed a reduction of manic and depressive symptoms in bipolar patients [50]. In addition, lithium orotate is available without a prescription, unlike lithium carbonate, which is considered a prescription drug by the Food and Drug Administration (FDA). Studies have also shown that the amino acid-derivative, taurine, as an alternative to lithium, blocks the effects of excess acetylcholine that contributes to bipolar disorder [51].

Numerous studies for bipolar disorder have been published that list specific lifestyle changes as well as amounts of dietary supplements that can be used to treat this disorder. A summary of these results is listed in Table 2.

Table 2. List of possible causes and treatments for bipolar disorder including specific doses as well as supplementary information


Schizophrenia is a mental disorder that disrupts a person's normal perception of reality. Schizophrenic patients usually suffer from hallucinations, paranoia, delusions, and speech/thinking impairments. These symptoms are typically presented during adolescence [52]. Disturbances in amino acid metabolism have been implicated in the pathophysiology of schizophrenia. Specifically, an impaired synthesis of serotonin in the central nervous system has been found in schizophrenic patients [53]. High doses (30 g) of glycine have been shown to reduce the more subtle symptoms of schizophrenia, such as social withdrawal, emotional flatness, and apathy, which do not respond to most of the existing medications [54-56]. An open-label clinical trial performed in 1996 revealed that 60 g of glycine per day (0.8 g/kg) could be given to schizophrenic patients without producing adverse side effects and that this dose led to a two-fold increase in cerebrospinal fluid (CSF) glycine levels [55]. A second clinical study treated patients with the same dosage divided into 3 doses within 1 week. This form of glycine treatment led to an eight-fold increase in CSF glycine levels [56].

The most consistent correlation found in one study that involved the ecological analysis of schizophrenia and diet concluded that increased consumption of refined sugar results in an overall decreased state of mind for schizophrenic patients, as measured by both the number of days spent in the hospital and poor social functioning [57]. That study also concluded that the dietary predictors of the outcome of schizophrenia and prevalence of depression are similar to those that predict illnesses such as coronary heart disease and diabetes.

A Danish study showed that better prognoses for schizophrenic patients strongly correlate with living in a country where there is a high consumption of omega-3 fatty acids [58]. Eicosapentaenoic acid (EPA), which is found in omega-3 fish oils, has been shown to help depressive patients and can also be used to treat schizophrenia [41,42,59]. Furthermore, studies suggest that supplements such as the commercially available VegEPA capsule, when taken on a daily basis, helps healthy individuals and schizophrenic patients maintain a balanced mood and improves blood circulation [59-65].

The VegEPA capsule contains:

• 280 milligrams of EPA from marine omega-3 fish oil

• 100 milligrams of organic virgin evening primrose omega-6 oil

• 1 milligram of the anti-oxidant vitamin E

• An outer capsule made out of fish gelatine

For schizophrenic patients, docosahexaenoic acid (DHA) supplements inhibit the effects of EPA supplements so it is recommended that the patient only takes the EPA supplement, which the body will convert into the amount DHA it needs [59-65]. Double-blind, placebo controlled studies, randomized, placebo controlled studies, and open-label clinical studies have all shown that approximately 2 g of EPA taken daily in addition to one's existing medication effectively decreases symptoms in schizophrenic patients [59,60,65].

Obsessive-Compulsive Disorder

Obsessive compulsive disorder (OCD) is an anxiety disorder that causes recurring stressful thoughts or obsessions that are followed by compulsions, which are repeated in an uncontrollable manner as a means of repressing the stressful thought [66]. It is well documented that selective serotonin reuptake inhibitors (SSRIs) help patients with OCD [67]. Therefore, it is clear that nutrients which increase serotonin levels will reduce the symptoms of OCD. As discussed earlier, the amino acid tryptophan is a precursor to serotonin, and tryptophan supplements (which are better than 5-Hydroxytryptophan) will increase serotonin levels and treat OCD [68].

A commercially available supplement called Amoryn has recently proven to help patients suffering from depression, anxiety, and OCD [69,70]. The main ingredient in Amoryn, St. John's wort, has been shown to help OCD patients better deal with their recurring thoughts and compulsions. Two double-blind, placebo-controlled studies were recently performed that compared the affects of a 900 mg daily dose of St. John's wort extract to 20 mg daily doses of Paroxetine (Paxil) or Fluoxetine; which are both SSRIs used to treat OCD. In comparison to patients taking Paxil, those who took the St. John's wort supplement showed a 57% decrease in OCD symptoms and were 47% less likely to exhibit side effects [69]. In comparison to patients taking Fluoxetine, consumption of the St. John's wort extract reduced 48% of OCD patient's symptoms [70]. These results clearly depict how the use nutritional supplements can be effective treatments for mental disorders.


Here we have shown just a few of the many documented nutritional therapies that can be utilized when treating mental disorders. Many of these studies were done in the 1970s and 1980s, but were soon discontinued because they were underfunded. Nutritional therapies have now become a long-forgotten method of treatment, because they were of no interest to pharmaceutical companies that could not patent or own them. Instead, the companies that funded most clinical research spent their dollars investigating synthetic drugs they could patent and sell; these drugs however usually caused adverse side effects.

There is tremendous resistance to using supplements as treatments from clinicians, mostly due to their lack of knowledge on the subject. Others rather use prescription drugs that the drug companies and the FDA researches, monitors and recalls if necessary. However, for some patients, prescription drugs do not have the efficacy of nutritional supplements and they sometimes have far more dangerous side effects. So for clinicians to avoid these supplement therapies because of a lack of knowledge and unwillingness to use treatments not backed by drug companies and the FDA, they are compromising their patients' recovery due to their own laziness or selfishness.

Clinical studies that show the ability of a prescription drug to effectively treat mental disorders will often argue that supplements as treatments, when unmonitored, are more risky than prescription drugs and may ineffectively treat a patient's symptoms. For example one study listed several methods of treatment, none of which include natural compounds, for OCD patients that include: megadoses of SSRIs, intravenous chlomipramine, oral morphine, deep brain stimulation, and functional neurosurgery [67]. Most of these treatments are invasive or unnatural and will inevitably cause severe side effects to the patient, whose symptoms will probably still reoccur over time. Another example of the literature scaring clinicians away from supplement therapies is an article that warns patients about the dangers of consuming high amounts of omega-3 fatty acids. This manuscript involves a patient who was taking approximately 10 times more than the recommended dose of omega-3 supplements [40]. Numerous studies have shown that up 2 grams of EPA (omega-3 fatty acid) taken daily is sufficient for decreasing symptoms of several mental health disorders with no side effects. This publication with a megadose of omega-3 fatty acids stresses the importance of monitoring the consumption of supplements as well as prescribed drugs, preferably through regular consultations with a licensed health care professional.

Proper medical diagnosis and a clear description of all possible treatment options should always be the first plan of action when treating mental disorders. However, the final decision on whether or not to try nutritional supplements as a treatment must be based on the patient preferences. Now with consumers becoming more interested in natural and holistic therapies, nutritional therapies have been well-received, and some studies are again underway in these areas. New well-designed clinical studies are being published daily on the positive effects of nutritional and supplement therapies on all types of disorders and diseases. It will take some time for clinicians to become educated on all the options available, but this is an important task that should not be ignored.

Those with influence in this field should continue to examine natural treatments on the scientific level in order to increase the availability of grant money for this type of research. This will lead to a surge of researchers who will submit proposals for grants enabling laboratories to further investigate the hypothesis that proper nutrition contributes to better mental health.

Psychiatrists treating patients with mental disorders should be aware of available nutritional therapies, appropriate doses, and possible side effects in order to provide alternative and complementary treatments for their patients. This may reduce the number of noncompliant patients suffering from mental disorders that choose not to take their prescribed medications. As with any form of treatment, nutritional therapy should be supervised and doses should be adjusted as necessary to achieve optimal results.


ADD: attention deficit disorder

ADHD: attention deficit hyperactivity disorder

CSF: cerebrospinal fluid

DHA: docosahexaenoic acid

EPA: eicosapentaenoic acid

FDA: Food and Drug Administration

GABA: gamma-aminobutyric acid

OCD: obsessive-compulsive disorder

PPARs: peroxisomal proliferator-activated receptors

PTSD: post-traumatic stress disorder

SAM: S-adenosylmethionine

SSRI: selective serotonin reuptake inhibitors


  1. Kessler RC, Chiu WT, Demler O, Walters EE: Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R).

    Archives of General Psychiatry 2005, 62(6):617-627. PubMed Abstract | Publisher Full Text OpenURL

  2. Demyttenaere K, Bruffaerts R, Posada-Villa J, Gasquet I, Kovess V, Lepine JP, Angermeyer MC, Bernert S, de Girolamo G, Morosini P, Polidori G, Kikkawa T, Kawakami N, Ono Y, Takeshima T, Uda H, Karam EG, Fayyad JA, Karam AN, Mneimneh ZN, Medina-Mora ME, Borges G, Lara C, de Graaf R, Ormel J, Gureje O, Shen Y, Huang Y, Zhang M, Alonso J, Haro JM, Vilagut G, Bromet EJ, Gluzman S, Webb C, Kessler RC, Merikangas KR, Anthony JC, Von Korff MR, Wang PS, Brugha TS, Aguilar-Gaxiola S, Lee S, Heeringa S, Pennell BE, Zaslavsky AM, Ustun TB, Chatterji S, WHO World Mental Health Survey Consortium: Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys.

    JAMA 2004, 291(21):2581-2590. PubMed Abstract | Publisher Full Text OpenURL

  3. Murray CJL, Lopez AD: The Global Burden Of Disease.

    World Health Organization 1996, 270. OpenURL

  4. American Psychiatric A: Diagnostic and Statistical Manual of Mental Disorders.

    Fourth edition, text revision Washington DC 2000. OpenURL

  5. Waring WS: Management of lithium toxicity.

    Toxicol Rev 2006, 25(4):221-230. PubMed Abstract | Publisher Full Text OpenURL

  6. Vieta E, Rosa AR: Evolving trends in the long-term treatment of bipolar disorder.

    World J Biol Psychiatry 2007, 8(1):4-11. PubMed Abstract | Publisher Full Text OpenURL

  7. Young SN: Clinical nutrition: 3. The fuzzy boundary between nutrition and psycopharmacology.

    CMAJ 2002, 166(2):205-209. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  8. Wurtman R, O'Rourke D, Wurtman JJ: Nutrient imbalances in depressive disorders. Possible brain mechanisms.

    Ann N Y Acad Sci 1989, 575:75-82. PubMed Abstract | Publisher Full Text OpenURL

  9. Young SN: Folate and depression–a neglected problem.

    J Psychiatry Neurosci 2007, 32(2):80-82. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  10. Hibbeln JR: Fish consumption and major depression.

    The Lancet 1998, 351(9110):1213. Publisher Full Text OpenURL

  11. Rudin DO: The major psychoses and neuroses as omega-3 essential fatty acid deficiency syndrome: substrate pellagra.

    Biol Psychiatry 1981, 16(9):837-850. PubMed Abstract OpenURL

  12. Rudin DO: The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: substrate beriberi.

    Med Hypotheses 1982, 8(1):17-47. PubMed Abstract | Publisher Full Text OpenURL

  13. Bell IR, Edman JS, Morrow FD, Marby DW, Mirages S, Perrone G, Kayne HL, Cole JO: B complex vitamin patterns in geriatric and young adult inpatients with major depression.

    J Am Geriatr Soc 1991, 39(3):252-257. PubMed Abstract OpenURL

  14. Eby GA, Eby KL: Rapid recovery from major depression using magnesium treatment.

    Med Hypotheses 2006, 67(2):362-370. PubMed Abstract | Publisher Full Text OpenURL

  15. Buist R: The therapeutic predictability of tryptophan and tyrosine in the treatment of depression.

    Int J Clin Nutr Rev 1983, 3:1-3. OpenURL

  16. Chouinard G, Young SN, Annable L: A controlled clinical trial of L-tryptophan in acute mania.

    Biol Psychiatry 1985, 20(5):546-547. PubMed Abstract | Publisher Full Text OpenURL

  17. Reis LC, Hibbeln JR: Cultural symbolism of fish and the psychotropic properties of omega-3 fatty acids.

    Prostaglandins Leukot Essent Fatty Acids 2006, 75(4–5):227-236. PubMed Abstract | Publisher Full Text OpenURL

  18. Tanskanen A, Hibbeln JR, Hintikka J, Haatainen K, Honkalampi K, Viinamaki H: Fish consumption, depression, and suicidality in a general population.

    Arch Gen Psychiatry 2001, 58(5):512-513. PubMed Abstract | Publisher Full Text OpenURL

  19. von Schacky C: A review of omega-3 ethyl esters for cardiovascular prevention and treatment of increased blood triglyceride levels.

    Vasc Health Risk Manag 2006, 2(3):251-262. PubMed Abstract | Publisher Full Text OpenURL

  20. Eritsland J: Safety considerations of polyunsaturated fatty acids.

    Am J Clin Nutr 2000, 71(1 Suppl):197S-201S. PubMed Abstract | Publisher Full Text OpenURL

  21. Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB: Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial.

    Arch Gen Psychiatry 1999, 56(5):407-412. PubMed Abstract | Publisher Full Text OpenURL

  22. National Institute of Mental Health: Depression.

    National Institute of Mental Health, National Institutes of Health 2000.

    US Department of Health and Human Services, Bethesda (MD) [Reprinted September 2002].


  23. Rush AJ: The varied clinical presentations of major depressive disorder.

    The Journal of clinical psychiatry 2007, 68(8 Suppl):4-10. PubMed Abstract | Publisher Full Text OpenURL

  24. Stockmeier CA: Neurobiology of serotonin in depression and suicide.

    Ann N Y Acad Sci 1997, 836:220-232. PubMed Abstract | Publisher Full Text OpenURL

  25. VanPraag HM: Depression, suicide and the metabolism of serotonin in the brain.

    J Affect Disord 1982, 4(4):275-290. PubMed Abstract | Publisher Full Text OpenURL

  26. Diehl DJ, Gershon S: The role of dopamine in mood disorders.

    Compr Psychiatry 1992, 33(2):115-120. PubMed Abstract | Publisher Full Text OpenURL

  27. Firk C, Markus CR: Serotonin by stress interaction: a susceptibility factor for the development of depression?

    J Psychopharmacol 2007, in press. PubMed Abstract | Publisher Full Text OpenURL

  28. Leonard BE: The role of noradrenaline in depression: a review.

    J Psychopharmacol 1997, 11(4 Suppl):S39-S47. PubMed Abstract OpenURL

  29. Petty F: GABA and mood disorders: a brief review and hypothesis.

    J Affect Disord 1995, 34(4):275-281. PubMed Abstract | Publisher Full Text OpenURL

  30. McLean A, Rubinsztein JS, Robbins TW, Sahakian BJ: The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression.

    Psychopharmacology 2004, 171(3):286-297. PubMed Abstract | Publisher Full Text OpenURL

  31. Agnoli A, Andreoli V, Casacchia M, Cerbo R: Effect of s-adenosyl-l-methionine (SAMe) upon depressive symptoms.

    J Psychiatr Res 1976, 13(1):43-54. PubMed Abstract | Publisher Full Text OpenURL

  32. aan het Rot M, Moskowitz DS, Pinard G, Young SN: Social behaviour and mood in everyday life: the effects of tryptophan in quarrelsome individuals.

    J Psychiatry Neurosci 2006, 31(4):253-262. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  33. Hoes MJ: L-tryptophan in depression.

    Journal of Orthomolecular Psychiatry 1982, 4:231. OpenURL

  34. Kravitz HM, Sabelli HC, Fawcett J: Dietary supplements of phenylalanine and other amino acid precursors of brain neuroamines in the treatment of depressive disorders.

    J Am Osteopath Assoc 1984, 84(1 Suppl):119-123. PubMed Abstract | Publisher Full Text OpenURL

  35. Maurizi CP: The therapeutic potential for tryptophan and melatonin: possible roles in depression, sleep, Alzheimer's disease and abnormal aging.

    Med Hypotheses 1990, 31(3):233-242. PubMed Abstract | Publisher Full Text OpenURL

  36. Ruhé HG, Mason NS, Schene AH: Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies.

    Mol Psychiatry 2007, 12(4):331-359. PubMed Abstract | Publisher Full Text OpenURL

  37. DeLeo D: S-adenosylmethionine as an antidepressant: A double blind trial versus placebo.

    Curr Ther Res 1987, 41(6):865-870. OpenURL

  38. Janicak PG, Lipinski J, Davis JM, Comaty JE, Waternaux C, Cohen B, Altman E, Sharma RP: S-adenosylmethionine in depression. A literature review and preliminary report.

    Ala J Med Sci 1988, 25(3):306-313. PubMed Abstract OpenURL

  39. Adams PB, Lawson S, Sanigorski A, Sinclair AJ: Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.

    Lipids 1996, 31(Suppl):S157-S161. PubMed Abstract | Publisher Full Text OpenURL

  40. Grubb BP: Hypervitaminosis A following long-term use of high-dose fish oil supplements.

    Chest 1990, 97(5):1260. PubMed Abstract | Publisher Full Text OpenURL

  41. Rihmer Z, Gonda X, Rihmer A: Creativity and mental illness.

    Psychiatr Hung 2006, 21(4):288-294. PubMed Abstract OpenURL

  42. Skutsch GM: Manic depression–a disorder of central dopaminergic rhythm.

    Med Hypotheses 1981, 7(6):737-746. PubMed Abstract | Publisher Full Text OpenURL

  43. Skutsch GM: Manic depression: a multiple hormone disorder?

    Biol Psychiatry 1985, 20(6):662-668. PubMed Abstract | Publisher Full Text OpenURL

  44. Naylor GJ: Vanadium and manic depressive psychosis.

    Nutr Health 1984, 3:79-85. PubMed Abstract OpenURL

  45. Naylor GJ, Smith AH: Vanadium: a possible aetiological factor in manic depressive illness.

    Psychol Med 1981, 11:249-256. PubMed Abstract OpenURL

  46. Botiglieri T: Folate, vitamin B12, and neuropsychiatric disorders.

    Nutr Rev 1996, 54:382-390. PubMed Abstract OpenURL

  47. Hasanah CI, Khan UA, Musalmah M, Razali SM: Reduced red-cell folate in mania.

    J Affect Disord 1997, 46:95-99. PubMed Abstract | Publisher Full Text OpenURL

  48. Osher Y, Bersudsky Y, Belmaker RH: Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study.

    2005, 66:726-729. PubMed Abstract | Publisher Full Text OpenURL

  49. Nieper HA: The clinical applications of lithium orotate. A two years study.

    Agressologie 1973, 14(6):407-411. PubMed Abstract OpenURL

  50. Sartori HE: Lithium orotate in the treatment of alcoholism and related conditions.

    Alcohol 1986, 3(2):97-100. PubMed Abstract | Publisher Full Text OpenURL

  51. O'Donnell T, Rotzinger S, Ulrich M, Hanstock CC, Nakashima TT, Silverstone PH: Effects of chronic lithium and sodium valproate on concentrations of brain amino acids.

    Eur Neuropsychopharmacol 2003, 13(4):220-227. PubMed Abstract | Publisher Full Text OpenURL

  52. Castle E, Wessely S, Der G, Murray RM: The incidence of operationally defined schizophrenia in Camberwell 1965–84.

    British Journal of Psychiatry 1991, 159:790-794. PubMed Abstract OpenURL

  53. van der Heijden DFFMMA, Tuinier S, Sijben AES, Kahn RS, Verhoeven WMA: Amino acids in schizophrenia: evidence for lower tryptophan availability during treatment with atypical antipsychotics?

    Journal of Neural Transmission 2005, 112(4):577-585. PubMed Abstract | Publisher Full Text OpenURL

  54. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP: Amelioration of negative symptoms in schizophrenia by glycine.

    Am J Psychiatry 1994, 151(8):1234-1236. PubMed Abstract | Publisher Full Text OpenURL

  55. Leiderman E, Zylberman I, Zukin SR, Cooper TB, Javitt DC: Preliminary investigation of high-dose oral glycine on serum levels and negative symptoms in schizophrenia: an open-label trial.

    Biol Psychiatry 1996, 39(3):213-215. PubMed Abstract | Publisher Full Text OpenURL

  56. Javitt DC, Silipo G, Cienfuegos A, Shelley AM, Bark N, Park M, Lindenmayer JP, Suckow R, Zukin SR: Adjunctive high-dose glycine in the treatment of schizophrenia.

    Int J Neuropsychopharmacol 2001, 4(4):385-391. PubMed Abstract | Publisher Full Text OpenURL

  57. Peet M: International variations in the outcome of schizophrenia and the prevalence of depression in relation to national dietary practices: an ecological analysis.

    British Journal of Psychiatry 2004, 184:404-408. PubMed Abstract | Publisher Full Text OpenURL

  58. Christensen O, Christensen E: Fat consumption and schizophrenia.

    Acta Psychiatr Scand 1988, 78(5):587-591. PubMed Abstract | Publisher Full Text OpenURL

  59. Peet M: Eicosapentaenoic acid in the treatment of schizophrenia and depression: rationale and preliminary double-blind clinical trial results.

    Prostaglandins Leukot Essent Fatty Acids 2003, 69(6):477-485. PubMed Abstract | Publisher Full Text OpenURL

  60. Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ: Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia.

    Am J Psychiatry 2002, 159(9):1596-1598. PubMed Abstract | Publisher Full Text OpenURL

  61. Puri BK, Richardson AJ, Horrobin DF, Easton T, Saeed N, Oatridge A, Hajnal JV, Bydder GM: Eicosapentaenoic acid treatment in schizophrenia associated with symptom remission, normalisation of blood fatty acids, reduced neuronal membrane phospholipid turnover and structural brain changes.

    Int J Clin Pract 2000, 54(1):57-63. PubMed Abstract OpenURL

  62. Richardson AJ, Easton T, Gruzelier JH, Puri BK: Laterality changes accompanying symptom remission in schizophrenia following treatment with eicosapentaenoic acid.

    Int J Psychophysiol 1999, 34(3):333-339. PubMed Abstract | Publisher Full Text OpenURL

  63. Richardson AJ, Easton T, Puri BK: Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with eicosapentaenoic acid.

    Eur Neuropsychopharmacol 2000, 10(3):189-193. PubMed Abstract | Publisher Full Text OpenURL

  64. Richardson AJ: The role of omega 3 fatty acids in behaviour, cognition and mood.

    Scandinavian Journal of Nutrition 2003, 47(2):92-98. Publisher Full Text OpenURL

  65. Yao JK, Magan S, Sonel AF, Gurklis JA, Sanders R, Reddy RD: Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia.

    Prostaglandins Leukot Essent Fatty Acids 2004, 71(3):171-176. PubMed Abstract | Publisher Full Text OpenURL

  66. American Psychiatric A: Quick Reference to the Diagnostic Criteria from DSM-IV-TR.

    Arlington, VA 2000. OpenURL

  67. Fontenelle LF, Nascimento AL, Mendlowicz MV, Shavitt RG, Versiani M: An update on the pharmacological treatment of obsessive-compulsive disorder.

    Expert Opin Pharmacother 2007, 8(5):563-583. PubMed Abstract | Publisher Full Text OpenURL

  68. Yaryura-Tobias JA, Bhagavan HN: L-tryptophan in obsessive-compulsive disorders.

    Am J Psychiatry 1977, 134(11):1298-1299. PubMed Abstract | Publisher Full Text OpenURL

  69. Szegedi A, Kohnen R, Dienel A, Kieser M: Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.

    British Medical Journal 2005, 330(7494):759. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  70. Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Murck H, Rosenbaum JF: A double-blind, randomized trial of St. John's wort, fluoxetine, and placebo in major depressive disorder.

    J Clin Psychopharmacol 2005, 25(5):441-447. PubMed Abstract | Publisher Full Text OpenURL

  71. Bell IR, Edman JS, Marby DW, Satlin A, Dreier T, Liptzin B, Cole JO: Vitamin B12 and folate status in acute geropsychiatric inpatients: affective and cognitive characteristics of a vitamin nondeficient population.

    Biol Psychiatr 1990, 27(2):125-137. Publisher Full Text OpenURL

  72. Green AR, Aronson JK: The pharmacokinetics of oral L-tryptophan: effects of dose and concomitant pyridoxine, allopurinol or nicotinamide administration.

    Adv Biol Psychiatr 1983, 10:67-81. OpenURL

  73. Cohen BM, Lipinski JF, Altesman RI: Lecithin in the treatment of mania: double-blind, placebo-controlled trials.

    Am J Psychiatr 1982, 139:1162-1164. PubMed Abstract | Publisher Full Text OpenURL

  74. Wozniak J, Biederman J, Mick E, Waxmonsky J, Hantsoo L, Best C, Cluette-Brown JE, Laposata M: Omega-3 fatty acid monotherapy for pediatric bipolar disorder: A prospective open-label trial.

    Eur Neuropsychopharmacol 2007, 17(6–7):440-447. PubMed Abstract | Publisher Full Text OpenURL

  75. Frangou S, Lewis M, McCrone P: Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomized double-blind placebo-controlled study.

    Br J Psychiatry 2006, 188:46-50. PubMed Abstract | Publisher Full Text OpenURL

  76. Rix K, Ditchfield J, Freed DL, Goldberg DP, Hillier VF: Food antibodies in acute psychoses.

    Psychol Med 1985, 15(2):347-354. PubMed Abstract OpenURL

  77. Davies S, Stewart A: Nutritional Medicine.

    London, Pan Books 1987, 403. OpenURL

  78. Tondo L, Rudas N: Course of seasonal bipolar disorder influenced by caffeine.

    J Affective Disorder 1991, 22:249-251. Publisher Full Text OpenURL

  79. Castrogiovanni P, Pieraccini F: Dietary interferences with lithium therapy.

    Eur Psychiatr 1996, 11:53-54. Publisher Full Text OpenURL

  80. Bernstein AL: Vitamin B6 in clinical neurology.

    Annal NY Acad Sci 1990, 585:250-260. Publisher Full Text OpenURL

  81. Edwin E, Holten K, Norum FR, Schrumpf A, Skaug OE: Vitamin B12 hypovitaminosis in mental diseases.

    Acta Med Scand 1965, 177:689-699. PubMed Abstract OpenURL

  82. Popper CW: Do vitamins or minerals (apart from lithium) have mood-stabilizing effects?

    J Clin Psychiatry 2001, 62(12):933-944. PubMed Abstract OpenURL

  83. Haellstroem T: Serum B12 and folate concentrations in mental patients.

    Acta Psychiatr Scand 1969, 45(1):19-36. PubMed Abstract | Publisher Full Text OpenURL

  84. Schorah CJ, Morgan DB, Hullin RP: Vitamin C concentrations in patients in a psychiatric hospital.

    Hum Nutr Clin Nutr 1983, 37C:447-452. OpenURL

  85. Milner G: Ascorbic acid in chronic psychiatric patients: a controlled trial.

    Br J Psychiatr 1963, 109:294-299. OpenURL

  86. Rimland B: Plasma vitamin C in the prevention and treatment of autism.

    Autism Res Rev Intl 1998, 12(2):3. OpenURL

  87. Muskiet FAJ, Kemperman RFJ: Folate and long-chain polyunsaturated fatty acids in psychiatric disease.

    J Nutr Biochem 2006, 17(11):717-727. PubMed Abstract | Publisher Full Text OpenURL

  88. Taylor MJ, Geddes J: Folic acid as ultimate in disease prevention: Folate also improves mental health.

    BMJ 2004, 328(7442):768-769. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  89. Cohen BM, Miller AL, Lipinski JF, Pope HG: Lecithin in mania: a preliminary report.

    Am J Psychiatr 1980, 137:242-243. PubMed Abstract | Publisher Full Text OpenURL

  90. Parker G, Gibson NA, Brotchie H, Heruc G, Rees AM, Hadzi-Pavlovic D: Omega-3 fatty acids and mood disorders.

    Am J Psychiatry 2006, 163(6):969-978. PubMed Abstract | Publisher Full Text OpenURL

  91. Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lönnqvist J: Is low dietary intake of omega-3 fatty acids associated with depression?

    Am J Psychiatry 2004, 161(3):567-569. PubMed Abstract | Publisher Full Text OpenURL

  92. International medical news group: Depression linked to lower omega-3 fatty acid levels.

    Family Practice news 2004., 34(8)



  93. Leaf A: The electrophysiologic basis for the antiarrhythmic and anticonvulsant effects of n-3 polyunsaturated fatty acids: heart and brain.

    Lipids 2001, 36(Suppl):S107-110. PubMed Abstract | Publisher Full Text OpenURL

  94. Lieb J: Linoleic acid in the treatment of lithium toxicity and familial tremor.

    Prostaglandins Med 1980, 4:275-279. PubMed Abstract | Publisher Full Text OpenURL

  95. Sabelli HC, Fawcett J, Gusovsky F, Javaid JL, Wynn P, Edwards J, Jeffriess H, Kravitz H: Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements.

    J Clin Psychiatry 1986, 47(2):66-70. PubMed Abstract OpenURL

  96. Simonson M: L-phenylalanine.

    J Clin Psychiatry 1985, 46(8):355. PubMed Abstract OpenURL

  97. Bellivier F, Leboyer M, Courtet P, Buresi C, Beaufils B, Samolyk D, Allilaire JF, Feindgold J, Mallet J, Malafosse A: Association between the tryptophan hydroxylase gene and manic-depressive illness.

    Arch Gen Psychiatr 1998, 55:33-37. PubMed Abstract | Publisher Full Text OpenURL

  98. Cassidy F, Murry E, Carroll BJ: Tryptophan depletion in recently manic patients treated with lithium.

    Biol Psychiatr 1998, 43:230-232. Publisher Full Text OpenURL

  99. Benkelfat C, Seletti B, Palmour RM, Hillel J, Ellenbogen M, Young SN: Tryptophan depletion in stable lithium-treated patients with bipolar disorder in remission.

    Arch Gen Psychiatry 1995, 52:154-155. PubMed Abstract OpenURL

  100. Sandyk R: L-tryptophan in neuropsychiatric disorders: a review.

    Intl J Neurosci 1992, 67:127-144. OpenURL

  101. Carney MWP, Chary TK, Bottiqlieri T, Reynolds EH: The switch mechanism and the bipolar/unipolar dichotomy.

    Br J Psychiatr 1989, 154:48-51. OpenURL

  102. Tolbert LC, Monti A, Walter-Ryan W, Alacron RD, Bahar B, Keriotis JT, Allison JG, Cates A, Antun F, Smythies JR: Clinical correlations of one-carbon metabolism abnormalities.

    Prog Neuropsychopharmacol Biol Psychiatr 1988, 12(4):491-502. Publisher Full Text OpenURL

  103. Carney MWP, Chavy TK, Bottiglieri T, Reynolds LH: Switch and S-adenosylmethionine.

    Ala J Med Sci 1988, 25(3):316-319. PubMed Abstract OpenURL

  104. Pacchierotti C, Iapichino S, Bossini L, Pieraccini F, Castrogiovanni P: Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry.

    Front Neuroendocrinol 2001, 22:18-32. PubMed Abstract | Publisher Full Text OpenURL

  105. Nurnberger JI, Adkins S, Lahiri DK, Mayeda A, Hu K, Lewy A, Miller A, Bowman ES, Miller MJ, Rau L, Smiley C, Davis-Singh D: Melatonin suppression by light in euthymic bipolar and unipolar patients.

    Arch Gen Psychiatry 2000, 57:572-579. PubMed Abstract | Publisher Full Text OpenURL

  106. Avery D, Lenz M, Landis C: Guidelines for prescribing melatonin.

    Ann Med 1998, 30:122-130. PubMed Abstract OpenURL

  107. Fekkes D, Pepplinkhuizen L, Verheij R, Bruinvels J: Abnormal plasma levels of serine, methionine and taurine in transient, acute, polymorphic psychosis.

    Psychiatry Res 1994, 51:11-18. PubMed Abstract | Publisher Full Text OpenURL