Depression – Environmental Causes and Natural Treatments

It’s not your brain chemicals. It’s the environment.


Depression has many causes.1 These include poor diet, nutritional deficiencies, food allergies and intolerances, stress, trauma, social and lifestyle factors, chronic infections, and toxicants. One notable mechanism by which these may cause symptoms is inflammation. It’s well passed time to move beyond the paradigm of a single-drug intervention. Rather, the complexity of depression demands a holistic assessment of one’s entire life and subsequent intervention on multiple levels simultaneously. Numerous clinical trials have substantiated such a natural treatment approach.

This is part 2 of a 3-part series on depression. In part-1 of this series, we deconstructed the fallacious science behind antidepressants. We also made introductory remarks about environmental causes and natural treatments for depression. With the assumption that readers have already viewed that material, I now proceed with this review, which continues into part 3.

Inflammation Associated with Depression

Inflammation is more frequently being discussed as a potential treatment target for depression.2–4 Three different meta-analyses have found differences in proinflammatory cytokines between patients with major depressive disorder and controls. These include interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1β, the soluble IL-2 receptor, the IL-1 receptor antagonist (IL-1ra), and C-reactive protein (CRP). It appears that there may be three causal pathways: depression to inflammation, inflammation to depression, and bidirectional relationships.5–7 In middle-aged men, high serum concentrations of homocysteine may be associated with depression.8

Depression is frequently associated with gastrointestinal inflammation, as well as a number of diseases in which inflammation plays a role. These include autoimmune, neurodegenerative, and cardiovascular diseases, as well as type-2 diabetes, cancer, and obesity.9–13 Hay fever, asthma, and urticaria have also been linked to depression, bipolar disorder, other mental disorders, and suicide. (See Appendix.) Depression, gastrointestinal permeability, and inflammation also seem to coincide.14

A case-control study found that major depression is associated with brain inflammation.15 Bipolar depressed patients have been found to have increased inflammatory markers which track linearly with symptoms. These include elevated CRP and elevated homocysteine, as well as accompanying lower levels of vitamin B12 and folic acid.16–18 Other kinds of immune dysfunction in bipolar depression have also been noted.19,20 A post-mortem study found significantly lower levels of reduced, oxidized, and total glutathione in all psychiatric conditions, suggesting a greater susceptibility to oxidative stress.21

Most importantly, inflammatory treatments such as cytokine therapy, multiple types of vaccines, and endotoxin administration have been shown to induce depressive symptoms, sometimes lasting several weeks. (See Appendix.) A systematic review and meta-analysis also found that anti-cytokine treatment improves depressive symptoms. They furthermore found that the effect was not associated with improvement in primary physical illness.22

So what does all this mean? It means depression can have actual physiological causes that you aren’t simply born with. The inflammation has to be caused somehow. It also means that anti-inflammatory effects may explain a part of the benefits of many dietary supplements I review in this series. However, we must take care to avoid a symptom management mindset, and instead seek to eliminate the root causes of inflammation. I will review many such underlying causes as well as therapies that have lead to documented improvements in both depression scores and inflammatory markers.

Head-to-Head and Adjunctive Clinical Trials of Antidepressants and Natural Medicines

A number of studies test natural medicines against antidepressants. These are called head-to-head trials. Other studies combine natural therapies with antidepressants and test the combination against either antidepressants alone, or placebo alone. These are called adjunctive trials.

In some instances head-to-head trials may actually underestimate the effectiveness of natural medicines due to unblinding bias. While there is an expectation of benefit within either group of a head-to-head trial, that expectation is probably greater within a drug group as compared to a dietary supplement group, owing to the side effects of drugs (see part-1). Though note that this only applies to trials where the patient is scoring their own depression. In trials where the physician is doing the scoring, it is not as clear cut how unblinding bias will affect them. Which treatment are they unconsciously rooting for?

In other instances, head-to-head trials at the very least further prove that antidepressants don’t work. For example, two studies found homeopathy is not any less effective than fluoxetine (Prozac).23 Some may interpret this as evidence that homeopathy works. A more biochemically plausible explanation is rather that Prozac doesn’t work.

Adjunctive trials should be viewed cautiously because often times the second intervention does not have an adequate control. If one group is receiving two interventions, and the other group is receiving only one intervention, the first group may have greater expectation of benefit, thus confounding results with a placebo effect. Ideally, the second group should receive the one intervention, plus a placebo. Or else, both groups should have all ingredients contained within a single capsule, so no one knows how many interventions they are receiving.

Although sometimes positive results of head-to-head or adjunctive trials might just be due to noise (small studies with small effect sizes), as a whole, these studies indicate that a number of natural therapies may be beneficial in the treatment of depression. This is especially the case when we consider that several of the interventions mentioned in this section also have standalone evidence from placebo-controlled trials, which I review later on.

Light Therapy

Light therapy outperformed fluoxetine in a trial of 122 patients with major depressive disorder. 44% achieved remission in the light therapy only group, 30% in the placebo group, and only 19% in the fluoxetine group. Note that the drug failed to outperform placebo.24 A systematic review and meta-analysis found light therapy to be an effective adjunct to antidepressants in major depressive disorder and bipolar depression without a seasonal pattern.25

A Review of Adjunctive Trials

A review of 40 clinical trials that used natural supplements as an adjunct to antidepressants found primarily positive results for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, fish oil, and vitamin D. It also found positive isolated studies for creatine, folinic acid, and an amino acid combination. No trials reported any major adverse effects.26 Some of these reviewed studies might have also had a third group which allowed for testing the nutrient head-to-head with the antidepressant, rather than only as an adjunct. It might be worth digging through their references to look for those. For example, in one adjunctive study of omega-3 fatty acids (EPA), there was also an EPA-only group which performed as well as the fluoxetine group.27 However, fish oil research should be interpreted with particular skepticism as previous authors have found no benefit in depression after adjusting for publication bias.28

It is worth noting that using SAMe to boost serotonin is still symptom management. Such supplements do little to address root causes of disease. The same goes for other serotonin-boosting supplements like L-typropthan, which performed as well as imipramine in one study.29

A more recent systematic review also suggested positive results for vitamin D as an adjunct.30


Saffron was found to be as effective as fluoxetine in three different trials. (See Appendix.) Other trials have found saffron to be as effective as imipramine and citalopram.31,32 A trial of 60 patients found no significant difference in the efficacy of curcumin when compared to fluoxetine (Prozac) in the treatment of major depression.33 Another trial found curcumin to be an effective adjunct to antidepressants.34 A trial tested a rhodiola extract against the drug sertraline. Both interventions outperformed placebo, although sertraline apparently did better. However, rhodiola was associated with less than half the risk of adverse effects as compared to the drug.35 A review of 29 studies testing St. John’s wort (hypericum) against depression was published in 2009. 18 trials tested against placebo, and 17 trials tested against various antidepressants drugs. The review concluded that hypericum is more effective than placebo and similar in effectiveness to antidepressants, but with fewer side effects.36 A 2015 review had similar conclusions, but gave more stress to the incompleteness of the research.37 Ayurvedic herbal treatment showed comparable results to clonazepam (Klonopin) in the treatment of generalized anxiety disorder with comorbid generalized social phobia.38 A systematic review and meta-analysis of trials that tested Chai Hu Shu Gan San (a traditional Chinese medicine) against fluoxetine found the herbs to have larger effects.39


A 2008 trial found magnesium to be as effective as imipramine in treating depression in diabetics, without any of the side effects of the drug. (See Appendix.)

A systematic review and meta-analysis found acetyl-L-carnitine to be effective in the treatment of depression, with efficacy similar to antidepressants, with fewer side effects.40

One trial found that vitamin C appeared to be an effective adjunct to fluoxetine. The combination group had significantly greater improvements in two out of three depression scores compared to the fluoxetine-only group.41 A trial tested vitamin C in combination with individually prescribed antidepressants against only individually prescribed antidepressants. The vitamin C group showed improvements that were significantly larger than the antidepressant-only group. However, this study had a large dropout rate and there were multiple types of antidepressants used.42 Another trial in patients with major depression did not find a significant difference between one group that took a combination of vitamin C and citalopram and another group that took a combination of vitamin C and placebo.43

Both endogenous and found in some foods, palmitoylethanolamide (PEA) showed efficacy as an adjunct to citalopram in one trial.44


Exercise is effective as both an adjunctive and standalone therapy in the treatment of major depressive disorder.45 A Cochrane review which included four head-to-head trials comparing exercise to pharmacological therapy found no significant difference.46


Patients with depression or anxiety disorders who were receiving standard medication were either assigned to a control group or a study group which was additionally treated with whole-body cold therapy for 15 days. By three weeks, the percentage of patients experiencing more than 50% reduction in depression scores was 34.6% in the study group and 2.9% in the control group. For anxiety disorders, these percentages were 46.2% and 0%.47

Pet Adoption

Voluntary pet adoption may be an effective adjunct to medication.48

Poor Diet as a Cause of Depression

Numerous studies – both observational and interventional – have implicated poor diet as a cause of depression.

A systematic review and meta-analysis found that pro-inflammatory diet is associated with a higher risk of depression.49 A study of 15,000 Spanish adults found that simply having a poor diet is associated with an increased chance of depression.50 Data from over 70,000 postmenopausal women suggest that a high glycemic index diet is also a likely risk factor for depression.51 Fruit and vegetable intake is inversely associated with depression. 52,53 A study of 281 young adults found that increasing intake of fruits and vegetables predicted improved emotional well-being on the following day.54 A study of over 263,000 people found that drinking 4 cans of diet soda a day is linked to a 30% higher chance of depression compared to non-drinkers. Drinking 4 cans of fruit punch was linked to a 38% higher risk compared to non-drinkers. On the other hand, drinking 4 cups of coffee was linked to a 10% lower chance compared to non-drinkers.55 Energy drink consumption has also been linked to depression, anxiety, and stress in young males.56 Intake of refined sugar and dairy predicted worse 2-year outcomes in schizophrenia.57 A prospective study found that sugar intake was associated with depression, with further evidence that there was no reverse causality.58 A study of 3,040 Australian adolescents found relationships between quality of diet and mental health. These results include a trend of mental health improving as diet quality was improved over the course over follow-up. There was also evidence that reverse causality was not the explanation.59 Dietary trans fatty acids are “strongly associated” with aggression.60

A 2014 systemic review selected 12 epidemiological studies to investigate the association between diet and mental health in children and adolescents. Overall, the review seems to support the notion that unhealthy dietary patterns may cause depression.61 Some of the studies the researchers chose to exclude from their review are still quite interesting. For example, in a study of 3486 middle-aged individuals, a processed food dietary pattern was associated with an increased risk of depression, whereas a whole food dietary pattern was associated with a decreased risk of depression.62

A randomized controlled trial found that a Mediterranean diet supplemented with nuts had an inverse association with depression compared to controls in elderly patients at high risk of cardiovascular disease. Though the association was not significant overall, it was significant when looking only at patients with diabetes.63 One small study found that reducing fat intake from 41% to 25% of the overall energy in a diet resulted in significant increases in ratings of anger-hostility, whereas controls saw a slight decrease.64 Conversely, a one-year RCT found that when obese people are placed on a low-fat, high-carbohydrate diet, their mood benefits relative to a high-fat, low-carbohydrate diet.65 Another RCT found that when people in a corporate setting are given either vegan dietary counseling or no counseling, the vegan diet is associated with a variety of improved outcomes, including mental health.66

A 2018 meta-analysis (Firth et al.) of RCTs testing dietary interventions found positive effects on depressive symptoms.67 However, most all studies were done in nonclinical populations (i.e. not diagnosed with depression). Overall, a relatively small benefit was found, and females appeared to benefit more than men. The only trial identified in the review that was done in a clinical population was the “SMILES” trial (Jacka et al. 2017). The authors tested dietary counseling versus a social support protocol in moderate to severe depression, and found greater improvements in the dietary counseling group relative to the controls, with an NNT of 4.1.68

In general, trials that use active controls are more believable, as they address the effects of unblinding bias. It is desirable to have patients in both groups have an “expectation” of benefit. This helps ensure that any reported benefit is not inflated by a placebo effect. Though Firth et al. found benefit whether trials were grouped by active or inactive controls, it is not surprising that trials that used active controls tended towards smaller benefit. The SMILES trial is thus doubly important in that it yielded a large benefit, while still employing an active control. This suggests the benefit of dietary interventions are likely to be much greater overall and that the reported lack of benefit in men may not apply to patients actually diagnosed with depression.

Many other studies, including at least four more meta-analyses or systematic reviews of observational studies, have found an association between poor quality diet and depression. (See Appendix.)

Overall, research suggests that a healthy diet with regards to mental health is one that emphasizes whole foods such as fruits, vegetables, and nuts, and that avoids all refined sugars, refined carbohydrates, processed foods, and trans fats. Raw fruits and vegetables appear to be better than processed. The role of a vegetarian versus an omnivore diet is not particularly clear and has some conflicting evidence. (See Appendix.) The best approach would probably be to consume flesh foods in moderation, and not in a processed form.

Nutrients, Nutraceuticals, and Depression

Related to poor diet, we now look at common nutritional deficiencies among depressed individuals, and at trials which have treated depression with nutrients and nutraceuticals. Note the overlap between the below interventions and those already discussed in the section on head-to-head and adjunctive trials.

B Vitamins

A 2017 review found that low levels of vitamin B (B1, B2, B3, B6, B9, B12) are common in patients with depression, and that vitamin B supplementation has been shown to improve depression outcomes.69 I mention some select studies here: In a controlled trial, B-vitamins were found to improve symptoms of depression and reduce homocysteine in certain adults over 65.70 Folate levels may be a predictor of treatment response and may also be a useful adjunct to antidepressants.71,72 A population based study of over 2,800 people found that those with the highest folate intake had a 45% lower chance of melancholic depression compared to those with the lowest intake.73 A prospective study of 2,313 Finnish men found that those who fell below the median folate intake had 3 times the risk of being diagnosed with depression during the follow-up period.74

Curcumin and Saffron

A 2016 meta-analysis of six trials found that curcumin is effective in the treatment of depression.75 A 2017 systematic review concluded that curcumin is a promising natural agent for many neuropsychiatric conditions, most notably major depression.76 At least three systematic reviews and meta-analyses have found saffron is more effective than placebo. And at least two more positive RCTs have been published since then. (See Appendix.) A 2017 trial tested low-dose curcumin, high-dose curcumin, and the combination of low-dose curcumin and saffron against placebo in patients with major depressive disorder. All three treatment groups saw significant reduction in depression and anxiety symptoms compared to controls.77

Vitamin D and Sunlight

Research is increasingly suggesting that low vitamin D levels is an effect, rather than a cause of disease.  Also, vitamin D technically does not meet the definition of a nutrient either, but I will discuss that some other time. And although sunlight is not a dietary nutrient and has many biological effects, for ease of discussion I include it here. Latitude correlates with suicide rate, suggesting lack of sunshine as a cause of depression.78,79 Lower levels of vitamin D appear to predict severity of depressive symptoms in young adult women.80 In one study low vitamin D was associated with an 11-fold increased risk of mood disorder in older adults.81 A study also found that there is a significant drop in Google searches relating to mental health during the summer, relative to the winter.82 A study in community-dwelling European men found the risk of depression was 70% higher across decreasing quartiles of vitamin D levels.83 A small study of 15 patients with seasonal affective disorder received either broad-spectrum phototherapy or a form of vitamin D. All patients receiving vitamin D improved in all measured outcomes, whereas no improvements were seen in the phototherapy group. Both groups saw increases in their vitamin D levels.84 Vitamin D deficiency is associated with anxiety and depression in fibromyalgia.85 In a study of 441 obese subjects with depression, one year of supplementation with vitamin D led to significant improvements in depression scores compared to baseline, whereas the placebo group saw no improvements compared to baseline.86 Vitamin D improved mood and blood pressure in diabetic women.87 A study of over 16,000 university students found that seasonal increases in sun time were associated with decreased mental health distress.88


A study found that young women who took a multivitamin plus 7 mg of zinc showed significant improvements in three different depression scores, whereas women who took only the multivitamin did not see any significant improvements.89 A meta-analysis found that lower levels of zinc are associated with depression.90 For example, one study found zinc deficiency was found in 36.6% of depressed geriatric patients, compared to only 14.4% of controls.91


A placebo-controlled trial of chromium supplementation in atypical depression found significant improvements compared to controls in diurnal variations of feelings, appetite increase, increased eating, and carbohydrate craving.92 Another small study of 15 patients with atypical depression showed responses in 70% of the chromium group, with zero responses in the placebo group.93


A meta-analysis of 8 studies found that supplementation with multivitamins/minerals improves measures of stress, mild psychiatric symptoms, anxiety, fatigue, and confusion, but not depression. The authors suggested that higher doses of nutrients may be called for.94

A trial in hospitalized acutely ill older patients found that oral nutritional supplementation led to a statistically significant benefit on depressive symptoms.95

In women over 50 supplementation with multivitamins/minerals and herbs led to acute improvements in mood compared to controls.96

A study of 492 patients with a range of mental illness were given “targeted nutrient therapy”. 382 patients complied for one year. 44.9% noted major improvement, 18.5% noted partial improvement, and 14.2% noted no improvement in three quality of life outcomes. In a group of 26 patients who did not receive the nutrient treatment, 19% noted major improvements, 19% noted partial improvement, and 62% noted no improvement. Hospital admission was lower in the treatment group.97

A study of 80 subjects found lower levels of vitamins A, C, and E in depressed patients compared to controls, and that supplementation led to improvements in depression scores.98

In the treatment of anxiety, naturopathic care involving a combination of dietary counseling, a multivitamin, ashwaganda, and deep breathing and relaxation techniques outperformed a control group which employed standardized psychotherapy, matched deep breathing and relaxation techniques, and a placebo.99

A study of 50 men found that supplementing with a multivitamin containing vitamins, minerals, antioxidants, and herbal extracts resulted in significant improvements in depression and anxiety scores, alertness, and general daily functioning compared to placebo controls.100

Magnesium and Calcium

A 2015 review and meta-analysis found that there may be an association between magnesium deficiency and depression.101 Another study of 5,708 community-dwelling adults found a significant relationship between magnesium intake and depression.102 The magnesium load test is considered by some to be more reliable than testing serum, red blood cell, whole blood, or white blood cell magnesium levels. One study found that these methods will miss deficiencies found by a magnesium loading test at least 40% of the time. The researchers furthermore found that a sample of 100 depressed patients revealed every single one of them had magnesium deficiency as determined by loading testing.103 A randomized open-label crossover trial suggests magnesium chloride supplementation may be beneficial.104 However, such results could be explained by placebo and nocebo effects experienced by the two respective groups.

Low dietary calcium is associated with self-rated depression in middle-aged Korean women.105


One study found that 51.4% of depressed patients had plasma CoQ10 values that were lower than the lowest plasma CoQ10 value detected in the controls.106 A controlled study in multiple sclerosis patients showed CoQ10 improved depression scores.107 However, a controlled trial in breast cancer patients did not lead to significant improvements in depression scores.108


A study of 986 older adults found a significant association between depression and anemia. 15% of depressed patients had anemia, whereas only 8% of controls did.109 A study of nearly 3,000 children and adolescents found an association between iron deficiency anemia and depressive disorder (OR=2.34) , bipolar disorder (OR=5.78), anxiety disorder (OR=2.17), and a number of other psychiatric disorders.110


A 2002 paper reviewed 5 studies that found an association between low selenium intake and poorer mood.111 A number of studies have come out since then. Prenatal selenium supplementation is associated with significantly lower postpartum depression in women compared to controls.112 A study of 978 young adults found that serum selenium concentrations are associated with depressive symptoms and negative mood.113 A study in nursing home residents found that 8 weeks of supplementation with selenium, vitamin C, and folate significant improved depression compared to placebo controls. Furthermore, selenium levels were significantly associated with depression. Although 67% of patients had low serum vitamin C, those levels were not significantly associated with depression.114

Vitamin C

Low plasma vitamin C has been associated with depression.115 Despite popular belief, vitamin C deficiency or depletion is common, with incidences ranging from 5% to 25% even in the United States and the UK. In other countries like India, it may be as high as 74%. (See Appendix.) A controlled trial in healthy young adults found 3000 mg of vitamin C improved depression scores, and increased frequency of sexual intercourse. Within just 2 weeks of supplementation, people who weren’t cohabiting with their partners reported having intercourse nearly 14 times per month, as compared to less than 4 times per month in the placebo group.116

Other Nutrients and Nutriceuticals

A systemic review looked at 21 controlled trials testing herbal and nutritional supplements in the treatment of mostly anxiety and depression. 71% of trials showed a positive direction of evidence. The authors concluded that there was strong evidence for the use of extracts of passionflower, kava, and combinations of L-lysine and L-arginine.117

Other nutraceuticals and interventions with controlled trials that suggest efficacy include dark chocolate, blue-green algae extract, goji berry juice, rhodiola extract, N-acetyl cysteine, ashwagandha extract, chlorella extract, chamomile extract, and aromatherapy.118–130

Food Allergies and Intolerances as a Cause of Depression

Food allergies and intolerances play a substantial role in depression and mental health in general.

A general population-based cohort study found an association with celiac disease and depression.131 A small double-blind cross-over study found that when irritable bowel syndrome patients that had celiac disease excluded were challenged with a gluten-containing diet, they reported higher depression scores compared to placebo. The authors suggest that patients with non-celiac gluten sensitivity may still feel better on a gluten-free diet, despite the continuation of gastrointestinal symptoms.132

Candida infection may actually be a trigger of celiac disease.133 I discuss the role of Candida and other chronic infections in depression in part-3.

A longitudinal study found increased levels of IgG antibodies to gliadin in patients hospitalized for acute mania compared to controls, but not so with other markers of celiac disease. No significant difference compared to controls was found at six month follow-up. Elevated antibody levels at follow-up were associated with re-hospitalization during the six month follow-up period.134

Intake of refined sugar and dairy predicted worse 2-year outcomes in schizophrenia.57

Anti-Saccharomyces cerevisiae antibodies (ASCA) is a marker of GI inflammation. In one study, an elevated ASCA conferred a 3.5-4.4 fold risk of bipolar disorder. ASCA also correlated with food antibodies in bipolar patients, and with antibodies to measles and T. gondii in patients with recent onset psychosis bipolar disorder.135

The Microbiome and Depression

A systematic review and meta-analysis found that probiotics are associated with a significant reduction in depression in both a healthy population and patients with major depressive disorder.136 One study found that consuming fermented foods (a source of probiotics) is associated with lower levels of social anxiety.137

As we saw earlier, gluten sensitivity may be a significant cause of depression. And gut bacteria may play a role in determining how sensitive individuals are to gluten.138

There are many environmental factors that lead to a distorted microbiome. Antibiotics are a prominent example, with history of antibiotic use being associated with depression.139 Though I will review this in more detail in the future, Selhub et al. provide a good start. Probiotics have pleiotropic effects that provide many potential ways in which they may positively affect mental health.140

Thyroid Disorders and Depression

A link between thyroid disorders and depression has been known for a long time.

For example, one study found that subclinical hypothyroid patients have symptoms of depression 45.6% of the time, where as only 20.9% of euthyroid patients did.141 Fifty-two percent of treatment resistant cases of depression appear to have subclinical hypothyroidism.142 Perhaps 20% of depressed patients carry thyroid antibodies, as compared to 5 to 10% of the general population.143

Some associations that have been found with depression are elevated T4 levels, low T3, elevated rT3, a blunted TSH response to TRH, antithyroid antibodies, and elevated CSF TRH concentrations.144–149 Overall, these authors suggest that using T3 as an adjunct, especially in treatment resistant cases, might improve outcomes. However, I would still call this symptom management and would rather that people investigate root-causes for the thyroid dysfunction, of which there could be many. Interestingly, in patients with subclinical hypothyroidism and depression, levothyroxine does not appear to improve symptoms.150

It should also be noted that I have already described the use of selenium in the treatment of depression. Selenium is required for the synthesis of thyroid hormone. Hence there could be a relation.


Hot water baths may be an effective treatment for depression.151

Continue to Part 3 – Chronic Infection, Toxicants, Stress, Trauma, and Lifestyle

In the third and final part of this series we review the roles of chronic infection, toxicants, stress, trauma, and lifestyle in depression. We also close with some treatment suggestions.

Rantala M, Luoto S, Krams I, Karlsson H. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate functions. Brain Behav Immun. 2018;69:603-617. [PubMed]
Haroon E, Raison C, Miller A. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology. 2012;37(1):137-162. [PubMed]
Kiecolt-Glaser J, Derry H, Fagundes C. Inflammation: depression fans the flames and feasts on the heat. Am J Psychiatry. 2015;172(11):1075-1091. [PubMed]
Miller A, Raison C. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22-34. [PubMed]
Howren M, Lamkin D, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71(2):171-186. [PubMed]
Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446-457. [PubMed]
Liu Y, Ho R, Mak A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012;139(3):230-239. [PubMed]
Tolmunen T, Hintikka J, Voutilainen S, et al. Association between depressive symptoms and serum concentrations of homocysteine in men: a population study. Am J Clin Nutr. 2004;80(6):1574-1578. [PubMed]
Simon G, Von K, Saunders K, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006;63(7):824-830. [PubMed]
Luppino F, de W, Bouvy P, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67(3):220-229. [PubMed]
Fehér J, Kovács I, Balacco G. [Role of gastrointestinal inflammations in the development and treatment of depression]. Orv Hetil. 2011;152(37):1477-1485. [PubMed]
Lasserre A, Glaus J, Vandeleur C, et al. Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: a prospective, population-based study. JAMA Psychiatry. 2014;71(8):880-888. [PubMed]
Bădescu S, Tătaru C, Kobylinska L, et al. The association between Diabetes mellitus and Depression . J Med Life. 2016;9(2):120-125. [PMC]
Calarge CA, Devaraj S, Shulman RJ. Gut permeability and depressive symptom severity in unmedicated adolescents. J. 2019;246:586-594. doi:10.1016/j.jad.2018.12.077
Setiawan E, Wilson A, Mizrahi R, et al. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry. 2015;72(3):268-275. [PubMed]
Dickerson F, Stallings C, Origoni A, et al. A combined marker of inflammation in individuals with mania. PLoS One. 2013;8(9):e73520. [PubMed]
Bai Y, Su T, Tsai S, et al. Comparison of inflammatory cytokine levels among type I/type II and manic/hypomanic/euthymic/depressive states of bipolar disorder. J Affect Disord. 2014;166:187-192. [PubMed]
Dickerson F, Katsafanas E, Schweinfurth L, et al. Immune alterations in acute bipolar depression. Acta Psychiatr Scand. 2015;132(3):204-210. [PubMed]
Permoda-Osip A, Dorszewska J, Skibinska M, Chlopocka-Wozniak M, Rybakowski J. Hyperhomocysteinemia in bipolar depression: clinical and biochemical correlates. Neuropsychobiology. 2013;68(4):193-196. [PubMed]
Rosenblat J, McIntyre R. Are medical comorbid conditions of bipolar disorder due to immune dysfunction? Acta Psychiatr Scand. 2015;132(3):180-191. [PubMed]
Gawryluk J, Wang J, Andreazza A, Shao L, Young L. Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol. 2011;14(1):123-130. [PubMed]
Kappelmann N, Lewis G, Dantzer R, Jones P, Khandaker G. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. October 2016. [PubMed]
Viksveen P, Fibert P, Relton C. Homeopathy in the treatment of depression: a systematic review. E. 2018;22:22-36. doi:10.1016/j.eujim.2018.07.004
Lam R, Levitt A, Levitan R, et al. Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016;73(1):56-63. [PubMed]
Penders T, Stanciu C, Schoemann A, Ninan P, Bloch R, Saeed S. Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis. Prim Care Companion CNS Disord. 2016;18(5). [PubMed]
Sarris J, Murphy J, Mischoulon D, et al. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016;173(6):575-587. [PubMed]
Jazayeri S, Tehrani-Doost M, Keshavarz S, et al. Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry. 2008;42(3):192-198. [PubMed]
Bloch M, Hannestad J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry. 2012;17(12):1272-1282. [PubMed]
Lindberg D, Ahlfors U, Dencker S, et al. Symptom reduction in depression after treatment with L-tryptophan or imipramine. Item analysis of Hamilton rating scale for depression. Acta Psychiatr Scand. 1979;60(3):287-294. [PubMed]
Brooke M. Vitamin D Supplementation May Help Ease Depression. Medscape. Published May 10, 2018. Accessed May 20, 2018.
Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi A, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med. 2004;4:12. [PubMed]
Ghajar A, Neishabouri S, Velayati N, et al. Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical Trial. Pharmacopsychiatry. 2017;50(4):152-160. [PubMed]
Sanmukhani J, Satodia V, Trivedi J, et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014;28(4):579-585. [PubMed]
Yu J, Pei L, Zhang Y, Wen Z, Yang J. Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. J Clin Psychopharmacol. 2015;35(4):406-410. [PubMed]
Mao J, Xie S, Zee J, et al. Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial. Phytomedicine. 2015;22(3):394-399. [PMC]
Ernst E. Review: St John’s wort superior to placebo and similar to antidepressants for major depression but with fewer side effects. Evid Based Ment Health. 2009;12(3):78. [PubMed]
Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016;5(1). doi:10.1186/s13643-016-0325-2
Tubaki B, Chandrashekar C, Sudhakar D, Prabha T, Lavekar G, Kutty B. Clinical efficacy of Manasamitra Vataka (an Ayurveda medication) on generalized anxiety disorder with comorbid generalized social phobia: a randomized controlled study. J Altern Complement Med. 2012;18(6):612-621. [PubMed]
Sun Y, Xu X, Zhang J, Chen Y. Treatment of depression with Chai Hu Shu Gan San: a systematic review and meta-analysis of 42 randomized controlled trials. B. 2018;18(1). doi:10.1186/s12906-018-2130-z
Veronese N, Stubbs B, Solmi M, Ajnakina O, Carvalho A, Maggi S. Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis. Psychosom Med. 2018;80(2):154-159. [PubMed]
Amr M, El-Mogy A, Shams T, Vieira K, Lakhan S. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013;12:31. [PubMed]
M Aburawi S. Effect of Ascorbic Acid on Mental Depression Drug Therapy: Clinical Study. J Psychol Psychother. 2014;04(01). doi:10.4172/2161-0487.1000131
Sahraian A, Ghanizadeh A, Kazemeini F. Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial. Trials. 2015;16:94. [PubMed]
Ghazizadeh-Hashemi M, Ghajar A, Shalbafan M-R, et al. Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial. J. 2018;232:127-133. doi:10.1016/j.jad.2018.02.057
Rethorst C, Trivedi M. Evidence-based recommendations for the prescription of exercise for major depressive disorder. J Psychiatr Pract. 2013;19(3):204-212. [PubMed]
Cooney G, Dwan K, Greig C, et al. Exercise for depression. Cochrane Database Syst Rev. 2013;(9):CD004366. [PubMed]
Rymaszewska J, Ramsey D, Chładzińska-Kiejna S. Whole-body cryotherapy as adjunct treatment of depressive and anxiety disorders. Arch Immunol Ther Exp (Warsz). 2008;56(1):63-68. [PMC]
Mota Pereira J, Fonte D. Pets enhance antidepressant pharmacotherapy effects in patients with treatment resistant major depressive disorder. J. 2018;104:108-113. doi:10.1016/j.jpsychires.2018.07.004
Tolkien K, Bradburn S, Murgatroyd C. An anti-inflammatory diet as a potential intervention for depressive disorders: A systematic review and meta-analysis. Clin Nutr. November 2018. [PubMed]
Sánchez-Villegas A, Henríquez-Sánchez P, Ruiz-Canela M, et al. A longitudinal analysis of diet quality scores and the risk of incident depression in the SUN Project. BMC Med. 2015;13:197. [PubMed]
Gangwisch J, Hale L, Garcia L, et al. High glycemic index diet as a risk factor for depression: analyses from the Women’s Health Initiative. Am J Clin Nutr. 2015;102(2):454-463. [PubMed]
McMartin S, Jacka F, Colman I. The association between fruit and vegetable consumption and mental health disorders: evidence from five waves of a national survey of Canadians. Prev Med. 2013;56(3-4):225-230. [PubMed]
Payne M, Steck S, George R, Steffens D. Fruit, vegetable, and antioxidant intakes are lower in older adults with depression. J Acad Nutr Diet. 2012;112(12):2022-2027. [PubMed]
White B, Horwath C, Conner T. Many apples a day keep the blues away–daily experiences of negative and positive affect and food consumption in young adults. Br J Health Psychol. 2013;18(4):782-798. [PubMed]
Hold the diet soda? Sweetened drinks linked to depression, coffee tied to lower risk. ScienceDaily. Published January 8, 2013. Accessed January 6, 2017.
Kaur S, Christian H, Cooper M, Trapp G. Energy drink consumption and mental health problems in young adults: A prospective investigation. J. 2017;8:119. doi:10.1016/j.jnim.2017.04.221
Peet M. International variations in the outcome of schizophrenia and the prevalence of depression in relation to national dietary practices: an ecological analysis. Br J Psychiatry. 2004;184:404-408. [PubMed]
Knüppel A, Shipley MJ, Llewellyn CH, Brunner EJ. Sugar intake from sweet food and beverages, common mental disorder and depression: prospective findings from the Whitehall II study. Scientific Reports. 2017;7(1). doi:10.1038/s41598-017-05649-7
Jacka F, Kremer P, Berk M, et al. A prospective study of diet quality and mental health in adolescents. PLoS One. 2011;6(9):e24805. [PubMed]
Golomb B, Evans M, White H, Dimsdale J. Trans fat consumption and aggression. PLoS One. 2012;7(3):e32175. [PubMed]
O’Neil A, Quirk S, Housden S, et al. Relationship between diet and mental health in children and adolescents: a systematic review. Am J Public Health. 2014;104(10):e31-42. [PubMed]
Akbaraly T, Brunner E, Ferrie J, Marmot M, Kivimaki M, Singh-Manoux A. Dietary pattern and depressive symptoms in middle age. Br J Psychiatry. 2009;195(5):408-413. [PubMed]
Sánchez-Villegas A, Martínez-González M, Estruch R, et al. Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med. 2013;11:208. [PubMed]
Wells A, Read N, Laugharne J, Ahluwalia N. Alterations in mood after changing to a low-fat diet. Br J Nutr. 1998;79(1):23-30. [PubMed]
Brinkworth G, Buckley J, Noakes M, Clifton P, Wilson C. Long-term effects of a very low-carbohydrate diet and a low-fat diet on mood and cognitive function. Arch Intern Med. 2009;169(20):1873-1880. [PubMed]
Katcher H, Ferdowsian H, Hoover V, Cohen J, Barnard N. A worksite vegan nutrition program is well-accepted and improves health-related quality of life and work productivity. Ann Nutr Metab. 2010;56(4):245-252. [PubMed]
Firth J, Marx W, Dash S, et al. The Effects of Dietary Improvement on Symptoms of Depression and Anxiety: A Meta-Analysis of Randomized Controlled Trials. Psychosom Med. 2019;81(3):265-280. [PMC]
Jacka F, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the “SMILES” trial). BMC Med. 2017;15(1):23. [PubMed]
Mikkelsen K, Stojanovska L, Prakash M, Apostolopoulos V. The effects of vitamin B on the immune/cytokine network and their involvement in depression. Maturitas. 2017;96:58-71. doi:10.1016/j.maturitas.2016.11.012
Lee H, Kim S, Sok S. Effects of Multivitamin Supplements on Cognitive Function, Serum Homocysteine Level, and Depression of Korean Older Adults With Mild Cognitive Impairment in Care Facilities. J Nurs Scholarsh. 2016;48(3):223-231. [PubMed]
Alpert J, Mischoulon D, Rubenstein G, Bottonari K, Nierenberg A, Fava M. Folinic acid (Leucovorin) as an adjunctive treatment for SSRI-refractory depression. Ann Clin Psychiatry. 2002;14(1):33-38. [PubMed]
Alpert M, Silva R, Pouget E. Prediction of treatment response in geriatric depression from baseline folate level: interaction with an SSRI or a tricyclic antidepressant. J Clin Psychopharmacol. 2003;23(3):309-313. [PubMed]
Seppälä J, Koponen H, Kautiainen H, et al. Association between folate intake and melancholic depressive symptoms. A Finnish population-based study. J Affect Disord. 2012;138(3):473-478. [PubMed]
Tolmunen T, Hintikka J, Ruusunen A, et al. Dietary folate and the risk of depression in Finnish middle-aged men. A prospective follow-up study. Psychother Psychosom. 2004;73(6):334-339. [PubMed]
Al-Karawi D, Al M, Tayyar Y. The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials. Phytother Res. 2016;30(2):175-183. [PubMed]
Lopresti A. Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies. J Psychopharmacol. January 2017:269881116686883. [PubMed]
Lopresti A, Drummond P. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Disord. 2017;207:188-196. [PubMed]
Terao T, Soeda S, Yoshimura R, Nakamura J, Iwata N. Effect of latitude on suicide rates in Japan. T. 2002;360(9348):1892. doi:10.1016/s0140-6736(02)11761-2
Davis G, Lowell W. Evidence that latitude is directly related to variation in suicide rates. Can J Psychiatry. 2002;47(6):572-574. [PubMed]
Kerr D, Zava D, Piper W, Saturn S, Frei B, Gombart A. Associations between vitamin D levels and depressive symptoms in healthy young adult women. Psychiatry Res. 2015;227(1):46-51. [PubMed]
Wilkins C, Sheline Y, Roe C, Birge S, Morris J. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006;14(12):1032-1040. [PubMed]
Ayers J, Althouse B, Allem J, Rosenquist J, Ford D. Seasonality in seeking mental health information on Google. Am J Prev Med. 2013;44(5):520-525. [PubMed]
Lee D, Tajar A, O’Neill T, et al. Lower vitamin D levels are associated with depression among community-dwelling European men. J Psychopharmacol. 2011;25(10):1320-1328. [PubMed]
Gloth F, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging. 1999;3(1):5-7. [PubMed]
Armstrong D, Meenagh G, Bickle I, Lee A, Curran E, Finch M. Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol. 2007;26(4):551-554. [PubMed]
Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008;264(6):599-609. [PubMed]
Vitamin D improves mood and blood pressure in women with diabetes. ScienceDaily. Published June 25, 2013. Accessed January 7, 2017.
Beecher M, Eggett D, Erekson D, et al. Sunshine on my shoulders: Weather, pollution, and emotional distress. J Affect Disord. 2016;205:234-238. [PubMed]
Sawada T, Yokoi K. Effect of zinc supplementation on mood states in young women: a pilot study. Eur J Clin Nutr. 2010;64(3):331-333. [PubMed]
Swardfager W, Herrmann N, Mazereeuw G, Goldberger K, Harimoto T, Lanctôt K. Zinc in depression: a meta-analysis. Biol Psychiatry. 2013;74(12):872-878. [PubMed]
Grønli O, Kvamme J, Friborg O, Wynn R. Zinc Deficiency Is Common in Several Psychiatric Disorders. PLoS One. 2013;8(12):e82793. [PMC]
Docherty J, Sack D, Roffman M, Finch M, Komorowski J. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract. 2005;11(5):302-314. [PubMed]
Davidson J, Abraham K, Connor K, McLeod M. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry. 2003;53(3):261-264. [PubMed]
Long S, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom Med. 2013;75(2):144-153. [PubMed]
Gariballa S, Forster S. Effects of dietary supplements on depressive symptoms in older patients: a randomised double-blind placebo-controlled trial. Clin Nutr. 2007;26(5):545-551. [PubMed]
Macpherson H, Rowsell R, Cox K, Scholey A, Pipingas A. Acute mood but not cognitive improvements following administration of a single multivitamin and mineral supplement in healthy women aged 50 and above: a randomised controlled trial. Age (Dordr). 2015;37(3):9782. [PubMed]
Gautam M, Agrawal M, Gautam M, Sharma P, Gautam A, Gautam S. Role of antioxidants in generalised anxiety disorder and depression. Indian J Psychiatry. 2012;54(3):244-247. [PubMed]
Cooley K, Szczurko O, Perri D, et al. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One. 2009;4(8):e6628. [PubMed]
Harris E, Kirk J, Rowsell R, et al. The effect of multivitamin supplementation on mood and stress in healthy older men. Hum Psychopharmacol. 2011;26(8):560-567. [PubMed]
Cheungpasitporn W, Thongprayoon C, Mao M, et al. Hypomagnesaemia linked to depression: a systematic review and meta-analysis. Intern Med J. 2015;45(4):436-440. [PubMed]
Jacka F, Overland S, Stewart R, Tell G, Bjelland I, Mykletun A. Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study. Aust N Z J Psychiatry. 2009;43(1):45-52. [PubMed]
Cox R, Shealy C, Cady R. Significant magnesium deficiency in depression. J Neurol Orthop Med Surg. 1996;(17):7-9.
Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. Song Y, ed. P. 2017;12(6):e0180067. doi:10.1371/journal.pone.0180067
Bae Y, Kim S. Low dietary calcium is associated with self-rated depression in middle-aged Korean women. Nutr Res Pract. 2012;6(6):527-533. [PubMed]
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Lower plasma Coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness. Neuro Endocrinol Lett. 2009;30(4):462-469. [PubMed]
Sanoobar M, Dehghan P, Khalili M, Azimi A, Seifar F. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial. Nutr Neurosci. 2016;19(3):138-143. [PubMed]
Lesser G, Case D, Stark N, et al. A randomized, double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment-related fatigue in newly diagnosed patients with breast cancer. J Support Oncol. 2013;11(1):31-42. [PubMed]
Onder G, Penninx B, Cesari M, et al. Anemia is associated with depression in older adults: results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2005;60(9):1168-1172. [PubMed]
Chen M, Su T, Chen Y, et al. Association between psychiatric disorders and iron deficiency anemia among children and adolescents: a nationwide population-based study. BMC Psychiatry. 2013;13:161. [PubMed]
Benton D. Selenium intake, mood and other aspects of psychological functioning. Nutr Neurosci. 2002;5(6):363-374. [PubMed]
Mokhber N, Namjoo M, Tara F, et al. Effect of supplementation with selenium on postpartum depression: a randomized double-blind placebo-controlled trial. J Matern Fetal Neonatal Med. 2011;24(1):104-108. [PubMed]
Conner T, Richardson A, Miller J. Optimal serum selenium concentrations are associated with lower depressive symptoms and negative mood among young adults. J Nutr. 2015;145(1):59-65. [PubMed]
Gosney M, Hammond M, Shenkin A, Allsup S. Effect of micronutrient supplementation on mood in nursing home residents. Gerontology. 2008;54(5):292-299. [PubMed]
Hamer M, Bates C, Mishra G. Depression, physical function, and risk of mortality: National Diet and Nutrition Survey in adults older than 65 years. Am J Geriatr Psychiatry. 2011;19(1):72-78. [PubMed]
Brody S. High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. Biol Psychiatry. 2002;52(4):371-374. [PubMed]
Lakhan S, Vieira K. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J. 2010;9:42. [PubMed]
Pase M, Scholey A, Pipingas A, et al. Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial. J Psychopharmacol. 2013;27(5):451-458. [PubMed]
Kim M, Nam E, Paik S. [The effects of aromatherapy on pain, depression, and life satisfaction of arthritis patients]. Taehan Kanho Hakhoe Chi. 2005;35(1):186-194. [PubMed]
Imura M, Misao H, Ushijima H. The psychological effects of aromatherapy-massage in healthy postpartum mothers. J Midwifery Womens Health. 2006;51(2):e21-7. [PubMed]
Lee I, Lee G. [Effects of lavender aromatherapy on insomnia and depression in women college students]. Taehan Kanho Hakhoe Chi. 2006;36(1):136-143. [PubMed]
Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmström C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-348. [PubMed]
Amagase H, Nance D. A randomized, double-blind, placebo-controlled, clinical study of the general effects of a standardized Lycium barbarum (Goji) Juice, GoChi. J Altern Complement Med. 2008;14(4):403-412. [PubMed]
Sarris J, Kavanagh D, Byrne G, Bone K, Adams J, Deed G. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl). 2009;205(3):399-407. [PubMed]
Genazzani A, Chierchia E, Lanzoni C, et al. [Effects of Klamath Algae extract on psychological disorders and depression in menopausal women: a pilot study]. Minerva Ginecol. 2010;62(5):381-388. [PubMed]
Amsterdam J, Shults J, Soeller I, Mao J, Rockwell K, Newberg A. Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: an exploratory study. Altern Ther Health Med. 2012;18(5):44-49. [PubMed]
Pratte M, Nanavati K, Young V, Morley C. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med. 2014;20(12):901-908. [PubMed]
Ayorech Z, Tracy D, Baumeister D, Giaroli G. Taking the fuel out of the fire: evidence for the use of anti-inflammatory agents in the treatment of bipolar disorders. J Affect Disord. 2015;174:467-478. [PubMed]
Panahi Y, Badeli R, Karami G, Badeli Z, Sahebkar A. A randomized controlled trial of 6-week Chlorella vulgaris supplementation in patients with major depressive disorder. Complement Ther Med. 2015;23(4):598-602. [PubMed]
Amsterdam JD, Panossian AG. Rhodiola rosea L. as a putative botanical antidepressant. P. 2016;23(7):770-783. doi:10.1016/j.phymed.2016.02.009
Ludvigsson J, Reutfors J, Osby U, Ekbom A, Montgomery S. Coeliac disease and risk of mood disorders–a general population-based cohort study. J Affect Disord. 2007;99(1-3):117-126. [PubMed]
Peters S, Biesiekierski J, Yelland G, Muir J, Gibson P. Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity – an exploratory clinical study. Aliment Pharmacol Ther. 2014;39(10):1104-1112. [PubMed]
Corouge M, Loridant S, Fradin C, et al. Humoral immunity links Candida albicans infection and celiac disease. PLoS One. 2015;10(3):e0121776. [PubMed]
Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Yolken R. Markers of gluten sensitivity in acute mania: a longitudinal study. Psychiatry Res. 2012;196(1):68-71. [PubMed]
Severance E, Gressitt K, Yang S, et al. Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder. Bipolar Disord. 2014;16(3):230-240. [PubMed]
Huang R, Wang K, Hu J. Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2016;8(8). [PubMed]
Hilimire M, DeVylder J, Forestell C. Fermented foods, neuroticism, and social anxiety: An interaction model. Psychiatry Res. 2015;228(2):203-208. [PubMed]
Orlando A, Linsalata M, Notarnicola M, Tutino V, Russo F. Lactobacillus GG restoration of the gliadin induced epithelial barrier disruption: the role of cellular polyamines. BMC Microbiol. 2014;14:19. [PubMed]
Lurie I, Yang Y, Haynes K, Mamtani R, Boursi B. Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study. J Clin Psychiatry. 2015;76(11):1522-1528. [PubMed]
Selhub EM, Logan AC, Bested AC. Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. J. 2014;33(1):2. doi:10.1186/1880-6805-33-2
Almeida C, Brasil M, Costa A, et al. Subclinical hypothyroidism: psychiatric disorders and symptoms. Rev Bras Psiquiatr. 2007;29(2):157-159. [PubMed]
Sintzel F, Mallaret M, Bougerol T. [Potentializing of tricyclics and serotoninergics by thyroid hormones in resistant depressive disorders]. Encephale. 2004;30(3):267-275. [PubMed]
Iseme R, McEvoy M, Kelly B, Agnew L, Attia J, Walker F. Autoantibodies and depression: evidence for a causal link? Neurosci Biobehav Rev. 2014;40:62-79. [PubMed]
Nierenberg A, Fava M, Trivedi M, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1519-30; quiz 1665. [PubMed]
Joffe R. Hormone treatment of depression. Dialogues Clin Neurosci. 2011;13(1):127-138. [PubMed]
Krishna V, Thunga R, Unnikrishnan B, et al. Association between bipolar affective disorder and thyroid dysfunction. Asian J Psychiatr. 2013;6(1):42-45. [PubMed]
Berent D, Zboralski K, Orzechowska A, Gałecki P. Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder. Mol Biol Rep. 2014;41(4):2419-2425. [PubMed]
Bocchetta A, Traccis F, Mosca E, Serra A, Tamburini G, Loviselli A. Bipolar disorder and antithyroid antibodies: review and case series. Int J Bipolar Disord. 2016;4(1):5. [PubMed]
Hage MP, Azar ST. The Link between Thyroid Function and Depression. Journal of Thyroid Research. 2012;2012:1-8. doi:10.1155/2012/590648
Loh HH, Lim LL, Yee A, Loh HS. Association between subclinical hypothyroidism and depression: an updated systematic review and meta-analysis. B. 2019;19(1). doi:10.1186/s12888-018-2006-2
Naumann J, Grebe J, Kaifel S, Weinert T, Sadaghiani C, Huber R. Effects of hyperthermic baths on depression, sleep and heart rate variability in patients with depressive disorder: a randomized clinical pilot trial. BMC Complement Altern Med. 2017;17:172. [PMC]