Depression, Melancholia, Bipolar Disorders

Paul L. Reller L.Ac. / Last Updated: August 03, 2017


Information Resources / Additional Information and Links to Scientific Studies

  1. A long list of adverse health effects from antidepressant medications has finally led to alarm at the enormous over-prescription of these drugs, and addition of multiple drugs in therapy when they do not work well. This 2009 list of adverse effects from the Harvard Medical School is extensive:
  2. A large 2013 study at various state hospitals in Turkey found that chronic use of antidepressant medications came with considerable risk and association with Metabolic Syndrome:
  3. A large 2015 retrospective study of the risk of autism from the taking of antidepressant medication in pregnancy, by experts at the University of Montreal, in Canada, found that in a study of over 140,000 pregnancies that risk of autism by age 7 was almost doubled with the taking of antidepressant medication during the second and third trimester. Prior studies have found considerable risk of lower birth weight and premature birth, as well as infant respiratory distress syndrome and withdrawal syndrome at birth. Surely, integration of a broader protocol to treat depressive mood disorders for women who may become pregnant is sensible, especially considering the high incidence of withdrawal syndromes and difficulty stopping the use of antidepressants:
  4. A 2010 study of acupuncture in the treatment of major depressive disorder, at the Massachusetts General Hospital, associated with Harvard Medical College, concluded that this treatment once or twice a week was effective:
  5. A 2010 review of selected treatments in Complementary and Integrative Medicine by The American Psychiatric Association Task Force at the Center for Women's Mental Health, Massachusett's General Hospital, looked at the present randomized controlled trials of common treatment protocols, such as acupuncture, herbal medicine, nutrient medicine, and psychotherapies, and found promising results in these studies:
  6. A 2012 review of scientific study of acupuncture to treat depressive disorders, conducted by Massachusetts General Hospital and Chengdu University of Traditional Chinese Medicine, in China, found that a meta-review of all available high quality data indicates that acupuncture is a potential effective monotherapy for depression, and a safe and well-tolerated adjunct therapy for those patients taking an antidepressant medication as well, reducing side effects as well as improving outcomes. As usual, the body of evidence from randomized controlled human trials is more limited than that of pharmaceuticals, and further study is recommended:
  7. A 2013 randomized controlled study at Southern Medical University School of Medicine, in Guangzhou, Guangdong, China, found that addition of a 6-week course of acupuncture therapy, 3 times per week, markedly improved the clinical response with use of Paroxetine (Paxil) for treatment of Major Depressive Mood Disorder. This effect was measurable 4 weeks after the course of acupuncture. Both manual and electroacupuncture were found effective, with insignificant variance between these methods:
  8. A 2015 meta-review of all published studies of acupuncture integrated into treatment for depression and schizophrenia, by the Radboud University Njmegan School of Medicine in The Netherlands, with the WHO Collaborating Center for Traditional Medicine and Kyung Hee University, in Seoul, South Korea, found that there is compelling evidence that acupuncture should be integrated into the standard treatment of depressive mood disorders, and schizophrenia as well:
  9. A 2010 review of Complementary alternative treatments for depression at Stanford University, near San Francisco, California, U.S.A. found that a study of published randomized trials showed that acupuncture, exercise, stress reduction, bright light exposure, and sleep regulation all hold "great promise", and that the evidence for St. Johns' Wort replacing FDA approved pharmaceuticals is not yet sufficiently compelling. Such recommendations from very conservative University Psychiatry departments such as Stanford are promising for Integrative Complementary Medicine:
  10. A 2016 randomized controlled human clinical trial of adjunct aerobic activity in the holistic protocol for treatment of Major Depression, at the University of Sao Paolo, in Brazil, showed that this 4-week increased aerobic activity and exercise protocol significantly improved functional capacity in patients treated for Major Depressive Disorder, and was associated with improved efficacy with antidepressant therapy, allowing for decreases in dosage and polypharmacy:
  11. A 2009 randomized, placebo-controlled study at Beijing Meitan General Hospital found that utilizing acupuncture with a lowered dose of antidepressant (1/2 to 1/3 or the dosage of Prozac) produced the same results in a Rating Scale for Depression, and improvement in symptoms of anxiety and fewer anti-depressant side effects:
  12. A 2013 randomized, placebo-controlled study at Nanjing University of Chinese Medicine, in Nanjing, China, Second Medical College, found that integrating a 6 week course of acupuncture into the treatment of depression with an SSRI medication improved the cure/markedly effective rate by 33.4 percent, and effectively treated insomnia, anxiety and somatization associated with depression, allowing a rate of reduction of the dosage of medication by over 19 percent from the group treated with SSRI medication alone:
  13. A 2012 study of acupuncture as part of the integrated treatment of Depressive Mood Disorders, at Kyung Hee University, in Seoul, South Korea, found that acupuncture stimulation at just 2 points, HT7 and ST36, daily for 7 days, significantly modulated the dopamine metabolism and turnover in the prefrontal-limbic system in laboratory animals with induced maternal stress depression, showing that even a short and simple course of acupuncture could benefit greatly the neurochemical imbalances in Depression. What is not apparent from these studies is that such acupuncture treatment also exerts many other beneficial effects to improve homeostasis, all of which will not be measured in modern scientific studies that are by design limited to specific effects:
  14. As far back as 1995 we see large long-term studies seeking answers to the high rate of non-adherence to medication strategies, even in a 3 month treatment period, and dissatisfaction of relief of symptoms. This large study by the University of Washington Medical School found that a multifaceted intervention helped to significantly improve effectiveness of treatment with patients suffering from Major Depressive Disorder:
  15. A 2016 study with metabolomics at the Chongqing Medical University, in Chongqing, China, used MRI spectroscopy to study the metabolic abnormalities seen in Major Depressive Disorder, and found that 6 nutrient metabolites were significantly deficient in the prefrontal cortex of laboratory animals, and 14 were excessive. Such study shows that potential for a restorative approach to these mood disorders, aiding brain metabolism as part of a more holistic approach:
  16. A 2012 study at the Beijing TCM Hospital Affiliated to the Capital Medical University, Beijing, China, found in a randomized controlled human clinical trial, that the curative rate for a short course of acupuncture (6 weeks) was equal to that with use of Prozac, with no side effects that are commonly seen with Prozac:
  17. A 2014 study at the Beijing University of Chinese Medicine and the Inner Mongolia Medical University demonstrated that electroacupuncture stimulation at DU20 and Yintang downregulated expression of the cytokines IL-1beta and IL-6 in the hippocampus of laboratory animals exposed to chronic restraint stress, which induced depressive mood symptoms, and increased the expression of TGF-beta. These findings show that this simple and common TCM treatment can modulate the imbalances that are a hallmark of human depression pathogenesis, both preventing and treating this disease:
  18. By 2002, numerous studies were being reviewed to address non-adherence to standard antidepressant treatment protocols, which for almost all patients consisted of variations of SSRI and SSNRI medication, or Lithium, with the increased knowledge of risks and side effects of other antidepressants, such as MAOI inhibitors, hypnotics,and tricyclic antidepressants. Integrated treatment protocol was not widely used. This Swiss meta-analysis admits that the large array of studies did not address which interventions could solve these problems:
  19. As far back as 1999, clinical studies demonstrated that sexual dysfunction secondary to the use of antidepressant drugs, especially SSRIs were affecting up to 60% of these patients with chronic use, and the industry sought to find a chemical solution:
  20. By 2002, a meta-analysis of studies of antidepressant-induced sexual dysfunction by the Lewin Group of Virginia, found that between 30-60% of SSRI users experienced some form of SSRI-induced sexual dysfunction over time, but that only 5 randomized controlled trials were found to evaluate this medical problem: http:/
  21. A study in 2008 at the Depression Clinical and Research Program at Massachusetts General Hospital in Boston found that Maca root alleviated SSRI-induce sexual dysfunction in a dose-related effect, and was well tolerated at high dosage:
  22. A study in 2013, at the START clinic for Mood and Anxiety Disorders, Toronto, Ontario, Canada, found that utilizing a 12-week simple acupuncture treatment course in patients with sexual dysfunction secondary to SSRI and SNRI drug therapy, where they found 50-90 percent of patients reported sexual dysfunction, resulted in significant relief of these adverse effects:
  23. Two large long-term studies of the parasitic disease Clostridium difficile, published in 2013 in the medical journal BMC Medicine (Harvard Medical School), a journal of negative results in biomedicine, found that common antidepressant medications, and a diagnosis of depression, were highly associated with the most common parasitic disease in older hospitalized patients, and increased risks of this parasitic infection of 36 to 47 percent, induced by changes in gut health. The antidepressants associated with the increased risk were Prozac, Remeron and Trazodone, all of which affect the serotonin and 5HT neurotransmitters and receptors, most of which are located in the gastrointestinal system, not the brain:
  24. By 2006, a large meta-analysis of non-compliance of standard drug therapies for depression still failed to find adequate critical appraisal and quality evidence on the variety of interventions that could be utilized to address the subject of large non-compliance with standardized pharmaceutical care of depressive disorders:
  25. A 2013 study authored by Dr. Ramin J. Mojtabai PhD, of the Johns Hopkins Bloomberg School of Public Health, reviewed over 5000 cases of Major Depressive Disorder (MDD) in a 2009-10 U.S. survey, and found that nearly 2/3 of these cases did not meet the criteria for the diagnosis of MDD, exposing an explosive growth in the prescription of antidepressants that was not justified:
  26. In 2007, an international conference sponsored by the European College of NeuroPsychology arrived at a consensus statement that found that more than 10% of unipolar depressive syndromes progressed to a bipolar syndrome due to medication, that sudden withdrawal of medication exposed patients to serious active drug withdrawal effects, and that drug protocol compliance may be difficult to achieve in clinical practice. An addition of other medical interventions was discussed as an appropriate adjunct to withdrawal of standard pharmaceutical medication during or after the resolution of depressive or manic episodes:
  27. Cognitive and behavioral psychotherapy is another significant tool in the integrated protocols recommended to treat depressive disorders, yet, like acupuncture and herbal therapies, this type of treatment must be individualized and designing clear scientific studies with randomized double-blinded placebo-controlled trials is very problematic. Even with these study design obstacles, cognitive and behavioral therapy has proven in meta-analysis by 2010 to be a moderately effective adjunct treatment, and the expansion of cognitive and behavioral therapy to improve patient sleep hygiene and resolve sleep disorders is proving to be very successful to resolve depressive mood disorder:
  28. A 2002 study of cognitive-behavioral and relationship-focused therapies to treat depressive disorders in adolescent patients by the esteemed University of Pittsburgh School of Medicine found that up to 87% of youths undergoing this type of therapy recovered from their depressive episodes with cognitive-behavioral therapy. Early treatment for depressive symptoms, with various adjunct treatments to cure rather than medicate, is important to individual quality of life:
  29. A 2002 study of the mood and somatic effects of various progesterone therapies, even one combined with bioidentical conjugated equine estrogen, or estrone, debunked the widely held belief that progesterone depresses mood. Such studies at the UCSF Women's Mood and Hormone Clinic have elucidated the role of hormonal imbalances in mood disorders for women dramatically:
  30. A 2008 study of Maca root at Victoria University in Australia found that there was efficacy for treatment of postmenopausal depression. The study found positive effects in reducing symptoms of both depression and anxiety:
  31. A 2010 study at the Mood Disorders Program at McMaster University in Ontario, Canada, found that dysregulation of adipokines, such as leptin, adiponectin, and resistin, was a link between depression, obesity, and metabolic syndrome:
  32. A 2013 study at the University of Wollongong School of Health Sciences and Antipsychotic Research Laboratory, in New South Wales, Australia, found that atypical antipsychotics (Abilify, Seroquel et al) have fewer acute extrapyramidal effects (tremors, bruxism, dystonia, akisthesia and parkinsonism), but serious metabolic side effects such as weight gain, midsection obesity, and type 2 diabetes, or Metabolic Syndrome, with long-term use. These experts recommended that with the explosive growth in prescription of these drugs, that a sensible integrated approach to preventing and treating these side effects in the long term needs to be initiated in the field:
  33. A 2013 study in Russia found that the atypical antipsychotic medication Solian (amisulpride - sold under a number of brand names) exerted negative effects on immune function through the Dopamine type 2 receptor antagonism, suppression of immune responses to antigens that normally initiate a T-cell response, and direct influence on immunocompetent cells. These effects in laboratory studies differed between subtypes of subjects, heightened in animals with more aggressive mood disorders:
  34. A 2004 study at King's College London, Institute of Psychiatry, in London, United Kingdom, found that while atypical antipsychotic medications are associated with lower extrapyramidal side effects than typical antipsychotic drugs, and less risk of clinical hyperprolactinemia, that these effects on the pituitary, and the hypothalamus/pituitary complex of the adrenal axis, by certain of these drugs are because this central command center of the brain is poorly protected by the normal brain blood barrier, and direct effects of these drugs account for the findings of elevated prolactin with chronic use, not the typical blocking of Dopamine type 2 and 3 receptors. The drugs noted for elevated prolactinemia include amisulpride (Solian), which still showed an incidence of extrapyrimidal side effects in clinical trials of short term use in over 10 percent of patients:
  35. A 2013 study at Emory University School of Medicine, Atlanta, Georgia, U.S.A. summarized a wealth of recent medical research on the mechanisms underlying neurotransmitter imbalance in neuropsychiatric disorders, pointing to the role of chronic inflammatory dysfunction in the depletion of the serotonin precursor tryptophan, as well as the regulation and metabolism of dopamine and glutamate. These innate immune responses may be triggered by chronic stress, heightened vigilance to the perception of threat, and chronic low-grade microbial infections, affecting not only the immune ability but the ability of the neurohormonal system. Obviously, a more complex and holistic restoration of homeostatic dysfunctions may be needed to really cure depression:
  36. A large cohort study in 2015, sponsored by the American Hearty Society, and led by experts at the Harvard T.H. Chan School of Public Health, showed that for patients over age 50, that prolonged periods of depression doubled the risk of a stroke later in life. The implications are that a more holistic treatment and prevention protocol is needed to actually prevent such serious health problems. Of course, taking medications for depression that increase cardiovascular risk as well makes no sense:
  37. A large cohort study of the use of Chinese Herbal Medicine in the treatment of mood disorder and sleep disorder in Taiwan, by experts at the Chung Shan Medical University, in Taichung, Taiwan, and the Beijing University of Chinese Medicine, in China, found that in 2016, that about 10 percent of patients used herbal medicine for sleep disorders, but that only about 2 percent used herbal medicine to treat Major Depressive Mood Disorder, and that only a handful used both modalities. The most commonly used herbs were Polygoni multiflori (He shou wu), Polygala tenuifolia (Yuan zhi), Ziziphi spinosae (Suan zao ren), and the common formulas Jia Wei Xiao Yao San, Chai Hu jia Long gu Mu li Tang, and Suan zao ren Tang. No safety concerns were noted. Such study in China shows that even in this culture, the belief that Chinese Herbal Medicine is an "alternative" is widely believed, and that pharmaceutical treatment is most effective and without adverse health effects. These beliefs are now being widely challenged in scientific study, though, but will be hard to reverse:
  38. A 2012 randomized controlled human clinical trial integrating St. John's Wort (Hypericum perforatum) with tricyclic antidepressants, a the Jundishapur University of Medical Sciences, in Ahvaz, Iran, found that the group combining these medications improved significantly more than the group using the pharmaceutical alone, and no adverse effects were noted. In addition, the group integrating the herbal extract with pharmaceutical medication reported fewer sexual side effects and improved sleep quality. The widespread prohibition against Hypericum for decades now in the West appears to be without basis in clinical practice:
  39. A 2010 study at the Medical University of Wien, Department of General Psychiatry, in Austria, found that St. John's Wort extracts differ in chemical constituents between various manufacturers and types of extraction, yet quality extracts were shown to be as effective as standard antidepressant drug therapy, and much better tolerated (nontoxic). It would be wise to get this herbal product from a professional that uses the highest quality professional herbal products:
  40. A 2008 meta-analysis of St. John's Wort, hypericum perforatum, by the Cochrane medical database system, which is the most widely used and respected, found that St. John's Wort was proven to be similarly effective as standard antidepressants, have fewer side effects, and proven to be superior in effect to placebo:
  41. A 2010 clinical study of St. John's Wort extract in Shanghai found that this herbal treatment produced significant decrease in response to stress in patients with irritable bowel syndrome after 8 weeks of use, and GI symptoms related to IBS were significantly reduced as well:
  42. A 2003 study by the University of Munster, Institute of Pharmacology, in Germany, found that St. John's Wort extract worked in a number of physiological ways to benefit patients with Major Depressive Disorder, including mild inhibition of reuptake of serotonin, norepinephrine, dopamine and inbibition of monoamine oxidase, all of which help keep sufficient levels of these neurotransmitters in the brain. The herb also was found to aid GABA and gluatmate receptor functions, upregulate 5-HT(2) receptors, downregulate beta-adrenergic receptors, reduced symptoms of akisthisia (immobility), and helped regulate genes that control the hypothalamic-pituitary-adrenal axis, or endocrine function. All of these mechanism are potentially very helpful in many syndromes with depression:
  43. A 2007 meta-analysis of studies concerning herbal treatment of depression and anxiety, conducted by the University of Queensland in Australia, found that evidence at that time supported St. John's Wort and Kava Kava, with robust high-quality clinical evidence, but that other promising herbal therapeutics still needed to be studied, with only proof or potential benefit so far in small studies of Passiflora incarnata, Rhodiola rosacea, and Scutellaria lateriflora (skullcap):
  44. A 2016 study at th Perelman School of Medicine at the University of Pennsylvania, U.S.A. showed that the Chinese herb Rhodiola rosea (Hong jin tian) was effective as an adaptogenic to stress, and affected various neurohormonal, neurotransmitter receptor, and metabolic pathways that could help improve mood disorders:
  45. A 2005 study at Kyunghee University, Seoul, South Korea, found that the Chinese herb Nelumbinis semen (Lian zi xin) increases the serotonin level in the hippocampus that is normally decreased in depression, making this herb potentially significant in the herbal protocol to treat depression:
  46. A 2014 study at Capital Medical University, in Beijing, China, found that key chemicals in the Chinese herb Yuan zhi (Polygala tenuifolia) showed significant antidepressant effects, inhibiting reuptake of serotonin, dopamine and norepinephrine at modest dose, and comparing well in animal studies to duloxetine:
  47. A 2016 study at Rutgers University, in the U.S., and the National Taiwan University found that the Chinese herb Gastrodia elata (Tian ma) showed significant anti-depressive effects and helped regulate monoamine neurotransmitters, making this common Chinese herb a valuable part of a holistic protocol to treat depression:
  48. A 2009 study at the University of Hong Kong School of Chinese Medicine found that a tincture of Bai shao (Paeonia lactiflora), with extraction of glycosides, exerted significant antidepressant activities via inhbition of monoamine oxidases and attenuation of oxidative stress in animal studies of chronic behavioral stress:
  49. Further studies at the University of Hong Kong found that glycosides of Paeonia lactiflora (Bai shao) increased the expression of brain-derived neurotrophic factor and nerve growth factor in both normal and chronic behaviorally stressed laboratory animals, potentially benefitting the pathology of behavioral depression:
  50. A 2010 systematic meta-review of all scientific randomized controlled trials of acupuncture for the treatment of depressive disorders at the University of Hong Kong, China, reviewed 207 such RCTs and concluded that acupuncture is both effective and safe in treating major depressive disorders and post-stroke depression. The efficacy in acupuncture alone was comparable to pharmacological therapy. No trials were designed to assess the use of acupuncture combined with anti-depressants. One should note the general agreement that a multi-disciplinary protocol should be utilized in depression:
  51. A 2009 randomized controlled study at the Beijing Mei Tan General Hospital, in China, found that adding acupuncture to treatment protocol and reducing dosage of fluoxetine (Prozac) achieved the same outcomes as the higher dosage of Prozac. Considering the warnings in recent years concerning long-term use of fluoxetine (suicidal thoughts, agitation, insomnia, weight loss, withdrawal symptoms, gastrointestinal irritation, mineral imbalance), and the side effects of nervousness, drowsiness, changes in sex drive, excessive sweating, and tactile hallucinations, - the addition of acupuncture to achieve lower dosage and fewer potential adverse effects seems sensible:
  52. A 2010 study at Seoul National University, Seoul, South Korea, found that both electroacupuncture and manual acupuncture stimulation stimulated neurogenesis in key areas of the brain, such as the dentate gyrus and hippocampus. These areas have been identified as areas experiencing loss of cell volume in chronic depressive mood disorders, and electroacupuncture at such common points as ST36 and DU20, at 15 and 25 Hz, has been shown to stimulate this neurogenesis, adding an aspect of restorative medicine that may be very important to resolving persistent depression:
  53. A 2011 study at Southern Medical University, in Guangzhou, China, notes that adult neurogenesis in the hippocampus is an observed phenomenon with antidepressant drug therapy, occurring after 3-6 weeks of therapy, and probably explains why antidepressant drugs are observed to have effects on depressive symptoms only after this length of time. Utilizing acupuncture stimulation and neurogenic herbal and nutrient chemistry provides the patient with this effect over time without drug dependency and adverse side effects:
  54. A 2007 study at the Yale University School of Medicine, New Haven, Connecticut, U.S.A. was one of a number of studies that showed that Major Depressive Mood Disorder is characterized by neurodegenerative structural and chemical changes in the limbic system, especially the hippocampus, and restoration of homeostatic regulation of neurogenesis and neuroplasticity appears to be the most promising factor in the resolution of chronic major depression:
  55. A 2007 randomized, controlled human clinical trial at Chongqing Medical University, in Chongqing, China, measured the effects of acupuncture on circulating levels of adiponectin and leptin, which are linked to depressive mood disorders as well as obesity and insulin resistant Metabolic Syndrome. A combination of electroacupuncture at ST25 and SP14, 0.8 and 3 Hz, with a common manual acupuncture stimulation at ST34, SP10, SP4 and ST44, resulted in significant normalization of adiponectin and leptin levels, while no changes were seen in controls:
  56. A 2012 study at the Maes Clinics in Bangkok, Thailand, found that in a study of patients diagnosed with depression, compared to normal control patients, that autoimmune anti-5-HT antibody activity was measured in over 54 percent of depressed patients, and only 5.7 percent of normal controls. Patients diagnosed with the type of depressive mood disorder called melancholia showed a 82.9 percent incidence of these autoimmune antibodies to the serotonin precursor 5-HT (5-hyroxytryptophan):
  57. A 2006 study at the Emory University School of Medicine, Atlanta, Georgia, U.S.A. describes the wealth of scientific information gathered in the last decade concerning the relationship between inflammatory response, neurohormonal regulation, and depressive mood disorders:
  58. The esteemed medical researcher Dr. Charles L. Raison M.D. explores the innate immune and stress responses that may be at the heart of depressive mood disorders, seeking to study a variety of holistic Complementary Medicine techniques to help reset the healthy homeostatic mechanisms we depend on, integrating these with standard therapy:
  59. Study in 2013 at La Trobe University, Melbourne, Australia, describes how many of the current effective therapies in the treatment of Major Depressive Disorder, including pharmaceuticals and exercise, may work by resetting homeostatic mechanisms in the thermoafferent pathway of the neurohormonal system. These researchers point out that current pharmacological therapy are not working well enough, with on 50 percent of patients recovering in less than 12 weeks, and 20 percent of all patients failing to adequately respond to all currently available treatments. The need for integration of holistic therapeutic protocols is now being taken seriously worldwide:
  60. An expert on Mind-Body medicine and the relationship between innate immune responses regulated by a complex balance of neurotransmitter/hormones, and the behavioral and cognitive responses that result in a syndrome of depression, often linked to metabolic syndromes, Dr. Charles L. Raison now practices at the Department of Psychiatry at the University of Arizona, Tempe, Arizona, U.S.A., and continues to elucidate the holistic explanation of depression:
  61. The work of such experts in Mind-Body medicine as Dr. Charles Raison has led to a quick expansion of such therapeutic techniques in standard medicine. Here, study at Boston University and Massachusetts General Hospital, through the Athinoula A. Martinos Center for Biomedical Imaging, showed that mindfulness and meditation produced a measured change in the right-left brain functions and amygdala, a center of emotional memory sorting. Such mindfulness training is now standard practice at many health centers, such as Kaiser Permanente, although the adoption of true meditative breathing and cognitive awareness techniques that are proven to be process-specific and should be integrated with Mindful Attention Training (MAT) are lacking. This research does reveal how a variety of techniques can be integrated to achieve the best outcome in depressive mood disorders. The fear of Complementary Medicine in standard medicine appears to be slowly dissolving:
  62. A 2012 review of scientific study of the omega-3 essential fatty acids EPA and DHA (eicosapentaenoic and docosahexaenoic acids), important in the formation of inflammatory mediators, healthy cell membranes, and hormones, by the University of the Sunshine Coast, in Maroochydore, Queensland, Australia, found that standard treatment quidelines now recommend these supplements, or increased intake in diet, for a variety of chronic disease states, including, but not limited to, coronary heart disease, rheumatoid arthritis, dementia, and depression. This medical school and university is exploring the many factors that could effect results of this therapy, including cell membrane health, genetic expression, other signaling pathways, and of course, healthy metabolite formation, especially with nutrient cofactors and liver health:
  63. A 2012 study at the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic, in Pennsylvania, US, found that the imbalance between omega-6 and omega-3 essential fatty acids, with a relative excess of arachidonic acid (derived mainly from meat in the diet), was a significant predictor of depression as a side effect of interferon therapy (e.g. treatment of Hepatitis C). It is hypothesized that a balance of essential fatty acids could improve neurohormonal health and aid homeostatic mechanisms to improve a majority of cases of depressive mood disorder:
  64. A 2012 study at the Klinika Psychiatrii Doroslych, in Poland, found that integrating omega-3 essential fatty acids with standard medications for treatment-resistant recurrent depression or bipolar affective disorder resulted in marked improvement in depression symptoms:
  65. A 2012 study at the Institute of Psychiatry and Clinical Psychology at the Catholic University of the Sacred Heart, in Rome, Italy, found that the omega-3 essential fatty acid DHA as consistently deficient in the blood plasma of patients with bipolar affective mood disorder, and that supplementation with DHA (krill oil) may provide a significant therapeutic effect, improving neurohormonal second messengers linked to the membrane phosphatidylinositol cycle. Of course, other aids, such as phosphatidylcholine and inositol hexacotinate, could be effective to achieve these goals as well:
  66. A 2003 study at the University of Bergen, in Bergen, Norway, found the high homocysteine levels, which are a marker of cardiovascular risk and problems with the detox metabolism and balance of taurine, cysteine and folates, are linked to depressive mood disorders, but not the levels of circulating active folates and Vitamin B12. Such study shows that a more complex set of imbalances exists that need a more holistic restorative approach in medicine: