Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota) acting in gut brain circuits. In this context several healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat have been inversely associated with depression risk and even have been postulated to improve depressive symptoms. In contrast, unhealthy western dietary patterns including the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat diary, biscuits, snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies. However, it is always difficult to conclude a real prospective causal relationship from these mostly retrospective studies as depressed individuals might also change their eating habits secondarily to their depression. Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression. At last, several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics), which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials.

By the year 2020, depression is projected to reach second place in the ranking of disability adjusted life years calculated for all ages by the World Health Organization [1]. Depression is a multifaceted condition with diverse biological and environmental causes and has therefore been bidirectionally associated with a 1.5 to 6 fold risk to develop cardiovascular diseases, diabetes, epilepsy, stroke, Alzheimer`s dementia and cancer [2,3,4,5,6,7,8]. Depression is highly associated with obesity, metabolic syndrome and type-2 diabetes, indeed, it has even been discussed to classify depression as metabolic syndrome type II [9,10,11,12,13,14,15,16,17,18,19,20]. Interestingly, obesity is prospectively related to depression and depression is predictive for the development of obesity [9,10,11,12,13,14,15,16,17,18,19,20]. In conclusion, depression is a strong and statistically significant predictor of dietary quality and body mass index, i.e. higher scores in depressive symptomatology are associated with lower scores in dietary quality and an increased body mass index [21].

Biological systems of nutritional influence and depression are highly connected, i.e. nutrition activates hormonal, neurotransmitter and signaling pathways in the gut which modulate brain functions like appetite, sleep, energy intake, neurogenesis, reward mechanisms, cognitive function and mood [2,20,22,23,24,25] see Fig. 1. These changes again modulate eating behavior and might chronically result in stress-related disorders, affective disorders and dementia. Some relevant known players of this complex interacting system are for example ghrelin, leptin, the lipid endocannabinoid system, insulin growth hormone (IGF), insulin, advanced glycosylation endproducts (AGEs), corticosteroids, cholecystokinin (CCK), neuropeptide Y (NPY), glutamate, glucose, insulin, GABA, gastrin-releasing peptide and brain-derived neurotrophic factor (BDNF) [2,20,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60].

Fig. 1

Environmental, social and psychological factors change the composition of nutrition which is consumed. The compounds of nutrition consumed again change gut microbiota and milieu. Gut hormones again change mood and stress level.

Fig. 1

Environmental, social and psychological factors change the composition of nutrition which is consumed. The compounds of nutrition consumed again change gut microbiota and milieu. Gut hormones again change mood and stress level.

Close modal

CCK is a classical gut hormone released in the small intestine when fats and proteins are ingested. CCK is, however also a transmitter in central and intestinal neurons. Of note, CCK is one of the most powerful experimental panic inductors and its bolus injection leads to panic attacks and increased stress hormones [26,29,30]. The blockade of CCK can be exerted by antidepressant drugs, reverses depressive behavior, prevents HPA axis hyperactivity and can even lead to mania [26,29,30].

Another intermediator is gastrin-releasing peptide, which acts in the hippocampus and in the amygdala, where it regulates synaptic plasticity, neurogenesis and aspects of anxious and depressive behavior [27].

NPY was initially described as a cotransmitter of sympathetic neurons because it stimulates stress response, food intake, sleep and inflammatory processes [28,35]. In this context, NPY integrates complex somatic symptoms of depression and anxiety states and has been found to play a role in the pathomechanisms of both anxiety and depression [35].

BDNF is a mediator of food intake control via reward-related behavior [25], modulates vagal afferent gastrointestinal impulses and thereby drives overeating and weight gain associated with increased meal size and frequency [2,31]. The deletion of BDNF leads to obesity, hyperphagia, overeating, weight gain and abdominal adipositas [31], which are often clinically often observed symptoms in depressed individuals. BDNF is involved in the vulnerability to depression and the effects of antidepressant treatment [2,25,32,33]. Additionally, BDNF modulates neuronal plasticity, forms neuronal networks, promotes neurogenesis, synaptogenesis and resilience to depressive disorders [33,34,37].

Despite growing evidence on the biology of ghrelin, relatively little is known about the exact molecular pathways responsible for the biosynthesis and release of ghrelin [38]. The consumption of low amounts of carbohydrates increases ghrelin [38]. Ghrelin regulates central system development and mood, exerts antidepressant effects in mice and men, influences the reward behavior and displays dopaminergic properties [2,39,40].

Antidepressant effects were reported following ghrelin administration in mice and men [41,42].

Leptin has been associated with increased body fat and can be triggered by specific macronutritients, i.e. a high-concentration-fructose diet [43]. Indeed, there might be specific macronutrients which are able to induce leptin resistance independently of the amount of body fat [43]. Leptin is highly associated with depressive symptoms, sleep disturbances, reward behavior, hippocampal plasticity, decreases the basal and feeding-stimulated dopamine release (also in neurons of the ventral tegmental striatum), increases locomotor activity and increases food intake [2,39,44,45,46,47]. Similarly as BDNF [48,49,50,51], leptin acts also via the glycogen synthase kinase-3beta which is a key regulator in controlling hippocampal cell proliferation, mood and response to psychiatric medications [2,44,45].

Due to the fact that IGF regulates hippocampal neurogenesis and sensitizes central insulin signaling, its absence leads to depressive symptoms, i.e. a blockade of peripheral IGF reduces exercise induced neurogenesis [52,53,54,55,56]. Correspondingly, in animal models of rats and mice an antidepressant trial of IGF was comparable with the behavioral effects of serotonergic antidepressants and improved frontal cortex neuroplasticity [53,57]. In line with this an intranasal administration of IGF has been discussed as a plausible and promising treatment option of depression [58].

Chronically impaired peripheral glucose metabolism is connected with late life depression [59]. Indeed, diabetes has been shown to affect the incidence of depression and depressive symptoms are predictive of poor glycemic control in type 2 diabetes mellitus patients and the development of diabetes [5,12,16,60]. In a large population based cohort study depressive symptoms have been shown to be significantly associated with glucose metabolism [12]. In line with this, hyperglycemia and poor glycemic control as measured by glycosylated hemoglobin have been found to reduce hippocampal brain volume 61]. In this context, poor glycemic control was found to be associated with both, poorer memory function and smaller hippocampal volumes [62]. In a recent cross-over, double-blind, placebo-controlled resting state functional imaging study, glucose ingestion induced significantly greater elevations in plasma glucose, insulin, GLP-1 and GIP, while feelings of fullness increased and prospective food consumption decreased relative to fructose. Furthermore, imaging findings suggest that glucose and fructose induce dissociable effects on resting state functional connectivity within the basal ganglia/limbic network, which are probably mediated by different insulin levels [63].

Moreover, hyperglycemia is thought to contribute to elevated serum concentrations of AGEs [64]. AGEs are prooxidant, cytotoxic substances contributing to chronic inflammation and diabetic complications [64,65,66]. AGEs correlate with insulin resistance and inflammation, which is changed in depressive patients [20,64]. Also altered cytokine levels had been repeatedly reported in depressed patients [67]. Interestingly, a recent proteomic study suggests that AGEs are involved in first episode major depressed patients, who have not been treated with antidepressants [68]. Indeed, an optimization of the glycemic control and associated prevention strategies might modify not only depression but also the occurrence of dementia [59].

Insulin resistance has further been linked to phosphoinositide 3-kinase (PI3K) signaling which again is central in the development of depressive symptoms [48,49,50,51,69]. Inhibition of PI3K leads to inactivity, memory loss and depressive and anxious behavior [48,49,50,51,69].

Nutrition directly influences intestinal microbiota, which again appear to influence the development of neurotransmitter brain systems and modulate affective and stress-related disorders and pain perception [70,71,72,73,74]. Perturbations and disturbances of microbiota with dietary changes or prebiotics, probiotics or antibiotics can lead to addictive or depressive behavior [75,76]. Consequently, restoring a disturbed gut microbiome might be a desirable treatment strategy for depression, especially as most of the clinically depressed patients additionally suffer from obesity, weight loss or gain, appetite disturbances and constipation [77,78,79]. In rodents the use of Lactobacillus sp., Bifidobacteria sp., L. helveticus, B. longum, L. rhamnosus, L. helveticus and Lactobacillus farciminis helped in the reduction of anxiety and depressive symptoms [78].

A first randomized controlled clinical trial shows that a 3-week consumption of a probiotic-containing drinks containing Lactobacillus casei Shirota can significantly improve mood at least in healthy volunteers [80]. Similarly, a 30-day consumption of a probiotic mixture containing Lactobacillus helveticus and B. longum reduced anxiety and depressive symptoms and cortisol in healthy persons [81]. In a randomized controlled trial L. casei Shirota, decreased anxiety but not depressive symptoms as measured via the BDI in patients with chronic fatigue syndrome [80].

Interestingly, also prebiotics result in healthy controls in lower cortisol levels at awakening and improved attention to positive stimuli in an emotional recognition task [82].

The analysis of fecal microbiota of depressed patients revealed an overrepresentation of Bacteroidales, underrepresentation of the Bacteroidetes phylum and Oscillibacter an underrepresentation of Lachnospiraceae and Alistipes and a decrease in Bacteroidetes [76,78]. Alistipes have been shown to be easily modified by a dietary intervention, where natural food consisting entirely of animal or plant products is used, increases the abundance of biletolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreases the levels of Firmicutes, which are able to metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii) [74].

In several prospective partly large studies an unhealthy western dietary pattern was associated with an increased prevalence of depression [83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103]. Moreover, the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat intake, biscuit snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies [83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103].

In recapitulation, in a recent large study with about 4500 healthy controls, specific dietary patterns (healthy; unhealthy; sweets; ‘Mexican' style; breakfast) predicted 39.8% of the total variance of depression incidence with or without diabetes [91].

On the other hand healthy foods such as the Japanese diet (fruit, soy products, vegetables, green tea) or Mediterranean diet or other healthy diets containing high amounts of olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy, unprocessed meat have been inversely associated with depression risk [83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103].

However, most of the present studies are retrospective studies, where the exact mechanisms linking mood and meal cannot fully be explained and remain rather correlative, as behavioral changes might determine meal choice long before depression finally occurs. Therefore prospective randomized controlled studies on dietary effects are needed, with one starting at the moment in Australia [90]. In a quasi-experimental study, which examined the impact of a vegan diet on emotional well-being and productivity a weekly dietary instruction for 18 weeks resulted in an improvement in depression, anxiety, and productivity in 292 individuals [94]. Interestingly, vegetarians reported better mood than omnivores despite their negligible intake of EPA/DHA [96,97], which has also been confirmed in a parallel arm, interventional two-week randomized controlled trial [96,97] on a 2 week subclinical level in healthy volunteers who consumed vegetarian food [96,97]. In a comparative study between a high- and a low-sucrose, low-fat, hypoenergetic diet 43% of the total daily energy versus 4% intake was sucrose. In this study in 42 women no differences have been found concerning mood and depression and hunger scores [98].

In a prospective cohort study to investigate the relations between dietary glycemic index, glycemic load, and other carbohydrate measures (added sugars, total sugars, glucose, sucrose, lactose, fructose, starch, carbohydrate) and depression in 87,618 postmenopausal women a progressively higher dietary glycemic index was found to be associated with increasing odds of incident depression [99]. Higher consumption of dietary added sugars was associated with increasing odds of incident depression [99]. Higher consumption of lactose, fiber, nonjuice fruit, and vegetables was significantly associated with lower odds of incident depression [99]. In elderly subjects a dietary coaching might be effectfull and result in a decrease in depressive symptoms and an enhanced well-being over 2 years and even less hospital admissions [100,101]. In a further randomized controlled trial, the mediterranean diet combined with nuts reduced the risk for depression [92]. In sixty subjects with metabolic syndrome a six month weight loss programme reduced not only body fat mass but depressive symptoms, anxiety, leptin and CRP and increased dopamine and serotonine [102]. Another study focused on long term effects of a low protein diet on depressive symptoms and the quality of life in elderly patients with Type 2 diabetes [103]. After randomly selection, patients were enrolled in a 30 months low protein diet on either 6 days a week or seven days a week. Although Creatine Clearance similarly decreased in both groups, depression score and cognitive outcome improved significantly more in the seven days a week group than in the 6 days a week [103]. Using evidence from a randomized depression prevention trial for older adults, it has been confirmed that coaching in healthy dietary practices are effective in the protection of episodes of major depression and in the reduction of depressive symptoms to an extent from 40% to 50% [100].

Intakes of magnesium, calcium, iron, and zinc were inversely associated with the prevalence of depressive symptoms [104]. Zinc and magnesium are potent antagonists of the NMDA receptor and the deficiency of both of them may lead to functional NMDA receptor hyperactivity. Several animal and human studies have shown that low dietary zinc plays a role in the reduction of depression. Recently, two prospective cohorts show that high dietary zinc intake was associated with a decreased incidence of depression in both men and women [105]. In a randomized, blinded and placebo-controlled study, zinc supplementation was shown to improve mood states and reduce anger and hostility [106].

Magnesium gates the activity of NMDA receptors and indeed magnesium restriction is associated with reduced amygdala-hypothalamic protein levels of GluN1-containing NMDA complexes [107,108]. A preclinical study showed that magnesium reduced depressive symptoms and increased the concentration of a NMDA receptor subcomponent (GluN2B) in the prefrontal cortex [109]. At least in animal trials, highly dosed magnesium increases plasticity and neurogenesis [110]. Moreover, in one randomized study magnesium proved to be comparably effective in the treatment of depression as imipramine, which is an extensively used, tricyclic and highly effective antidepressant drug [111]. Therefore it has been hypothesized that oral administration of magnesium might support an antidepressant effect [112,113].

Increased polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) concentrations, and high concentrations of plasma total n-3 fatty acids, docosahexaenoic acid, eicosapentaenoic acid, α-linoleic acid, and linoleic acid, were associated with lower scores in the depression scale used [113,114]. Accordingly, fish consumption has been associated with resilience to depression [115]. However, about 97 double-blind, placebo-controlled, randomized controlled trials on the treatment of depression with PUFAs have been performed since 1965 [116]. In a recent meta-analysis no significant effects of omega-3 FA have been been found in the treatment of depression [116]. Most of the investigations have been performed in small samples and data are mixed [117]. However, the positive effects of fish consumption on depressive disorders might not be exclusively connected with PUFAs as e.g. tyrosine is present in high concentrations in many fishes (160% in tuna when compared with chicken) [118,119]. Tyrosine is a biological precursor of dopamine, norepinephrine, and epinephrine, a component of thyroxine and triiodothyronine (hypothyreosis is common in 30% of depressive patients) and its deficiency has been implicated in depression [119,120,121,122].

Chromium plays a crucial role in glucose and fat metabolism and improves insulin sensitivity in the hypothalamus, which enhances hypothalamic function by increasing glucose use, leading secondarily to an increased synthesis of serotonin, norepinephrine and melatonin [2,123]. Three pilot trials of chromium indicate an antidepressant effect in patients with unipolar depression when used as adjunctive or monotherapy [2,124,125,126].

According to the observation that oxidative stress and inflammation have been connected to the pathophysiology of depression subjects with a diagnosis of major depression consume less fruits, legumes, nuts and seeds, vitamin C, beta carotene, lutein, and zeaxanthin than controls [127]. In two to 28-day lasting, randomized, double-blind, placebo controlled studies, vitamin C was found to have an equivalent effect as a very strong antidepressant medication, i.e. amitriptyline 150 mg/d [128,129]. In a recent placebo controlled randomized clinical trial adding vitamin C to citalopram did not increase the efficacy of citalopram in major depressed patients [128].

Several reports indicate a high prevalence of folic acid deficiency among patients suffering from psychiatric conditions such as depression, bipolar disorder and cognitive dysfunction disorders [2,129]. Adequate levels of folate are essential for proper brain functioning [2,130,131]. Folate, with vitamins B12 and B6 as catalysing cofactors, influences cognitive performance and mood [2,132,134]. Treatment with vitamin B6, vitamin B12, and folic acid reduces the hazard of a major depressive episode compared with placebo among survivors of a stroke and reduces the risk to re-experience a major depressive episode for 7 years about 50% [133,134]. Several trials have demonstrated efficacy of folic acid in the treatment of unipolar depression [2,135]. However, in a recent meta-analysis of 52 randomized controlled trials the number of available trials remains small and heterogeneity between studies high. The results of these meta-analyses suggest that treatment with folate and vitamin B12 does not decrease the severity of depressive symptoms over a short period of time, but may be helpful in the long-term management of special populations [133,134].

In a randomised, double blind, parallel group, placebo-controlled trial in which participants, aged 14-24 years, at increased familial risk of mood disorder, were randomized to folic acid (2.5 mg daily) or identical placebo liquid for a maximum of 36 months the incidence of mood disorder in the folic acid and placebo groups were 14.3% and 17.9% respectively [136]. This effect was not statistically significant, however, there was post-hoc evidence that folic acid delayed the time to onset of mood disorder in those participants who became unwell [136].

In a cohort of 1745 pregnant Japanese women a higher intake of levels of yogurt and calcium was independently related to a lower prevalence of depressive symptoms during pregnancy [137]. The amount of calcium is proportional to the quantity of activated CaMKII [138]. A calcium influx during LTP induction triggers the activation of calcineurin and Calcium/calmodulin-dependent protein kinase II (CaMKII) in dendritic spines [138]. CaMKII activation has been linked to antidepressant treatment mechanisms [139]. However, there is no direct causal link between central effect and peripheral absorbed calcium, so in a recent epidemiological study the supplementation of vitamin D and calcium in about 36.000 postmenopausal women no significant effect on mood outcome has been observed [140].

In a large sample of 12.500 adults higher vitamin D values showed less incidence for depressive disorders and also depression related personality traits seem to correlate with vitamin D serum level, i.e. vitamin D is connected to openness and extraversion [141,142]. In terms of treatment vitamin D has been suggested to be helpful in subgroups of depressed persons, i.e. patients with saisonal affective disorder, less activity and older age [143].

It has been shown that D-serine interacts with the GluN1 unit of the NMDA receptor. In animal studies a single and acute D-serine administration leads to several behavioural effects of an antidepressant-like type which are for example reduced immobility in the forced swim test beneath many others [144]. Elevated D-serine concentrations in the central nervous system might lead to a depression-protected phenotype in mice [145]. Authors from these preliminary basic research studies suggest that chronic dietary D-serine supplementation might lead to improvement of mood disorders [145].

However, nutritional interventions for major depression have not been studied extensively yet and there are only pilot studies available. Therefore, to the knowledge of the author, there is no high level evidence (large prospective RCTs, meta-analyses) for an effective nutritional intervention for the treatment of major depression. Accordingly, the current standard treatment guidelines do not include any nutritional aspect for the prevention or treatment of major depression.

At least in terms of cardiovascular protection recent meta-analyses show that several medications (statins, aspirin, beta-blockers, fibrates, niacin, ACE inhibitors) do not reach the effect size of successful life style interventions as Mediterranean diet, consumption of fruits and vegetables, moderate alcohol use, smoking cessation and physical activity [146]. However, the adherence to life style modifications might be less feasible for depressed patients. However, a recent randomized, double-blinded, multicentre, two arm-parallel clinical trial, with a 12 month follow-up showed in a sample of 273 primary care patients that hygienic-dietary written recommendations on diet, exercise, light exposure and sleep hygiene were not successful [147]. In the last years several medications focusing on metabolic abnormalities have been proposed in the treatment of depression.

Pioglitazone, which is an insulin sensitizer acts as adjunctive therapy of depressive symptoms in mice and men [148,149]. In a parallel-arm, double-blind, placebo-controlled design in 138 healthy, overweight women food take inhibitors N-oleyl-ethanolamine (NOE) and epigallocatechin-3-gallate (EGCG) improved insulin resistance and depressive symptoms and binge eating with a high significance [150]. Furthermore, green tea extract consisting of polyphenols, particularly catechins such as EGCG, caffeine, and theanine share an overlap in activity of at least one biochemical pathway, the N-methyl-D-aspartate receptor (NMDAR) pathway. Along this line, beneficial effects of green tea on cognitive functioning [151], in particular, on working memory processing at the neural system level suggested changes in short-term plasticity of parieto-frontal brain connections [152]. Additionally, evidence was found that the insulin sensitizer pioglitazone in a double-blind placebo-controlled study in 40 patients with major depression showed superiority over placebo during the course of the trial. Therefore the authors state that pioglitazone is a safe and effective adjunctive short-term treatment in patients with moderate-to-severe MDD even in the absence of metabolic syndrome and diabetes [153]. Resulting from a present clinical study in depressive patients with diabetes mellitus treated with metformin authors raise the possibility that supplementary administration of antidiabetic medications may enhance the recovery of depression [154].

Statins have anti-obese properties and their use was associated with a significant reduced occurrence of depression at least in individuals who have had a cardiac event in a prospective clinical trial [155]. In a placebo controlled clinical trial, augmentation of citalopram with atorvastatin improved depressive symptoms assessed with the Hamilton depression rating scale [156]. Also a GLP-1 analogue therapy, i.e. exenatide has been discussed to exert antidepressant properties [157]. As compared with new insulin, treatment satisfaction, well-being score and the Hospital Anxiety and Depression Scale scores were significantly reduced in exenatide as compared with insulin-treated patients. Although exenatide and insulin appear to have similar efficacy for the treatment of type 2 diabetes mellitus, exenatide affects both physiological and psychological parameters and might be used as an adjunctive therapy for depression in the context of diabetes [157]. In addition, the use of gram-negative antibiotics has been discussed to offer a potential therapeutic approach for the adjuvant treatment of depression [158].

None of the contributing authors state any conflict of interest.

Reddy MS: Depression: The Disorder and the Burden. Indian J Psychol Med 2010;32:1-2.
Lang UE, Borgwardt S. Molecular mechanisms of depression: perspectives on new treatment strategies. Cell Physiol Biochem 2013;31:761-77.
Hesdorffer DC, Hauser WA, Annegers JF, Cascino G: Major depression is a risk factor for seizures in older adults. Ann Neurol 2000;47:246-249.
Ramasubbu R, Patten SB: Effect of depression on stroke morbidity and mortality. Can J Psychiatry 2003;48:250-257.
Nouwen A, Lloyd CE, Pouwer F: Depression and type 2 diabetes over the lifespan: a meta-analysis. Response to Mezuk et al. Diabetes Care 2009;32:e56-e57.
Penninx BW, Guralnik JM, Pahor M, Ferrucci L, Cerhan JR, Wallace RB, Havlik RJ: Chronically depressed mood and cancer risk in older persons. J Natl Cancer Inst 1998;90:1888-1893.
Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D, Duara R, Kukull WA, Chui H, Edeki T, Griffith PA, Friedland RP, Bachman D, Farrer L: Depression as a risk factor for Alzheimer disease: the MIRAGE Study. Arch Neurol 2003;60:753-759.
Van der Kooy K, van Hout H, Marwijk H, Marten H, Stehouwer C, Beekman A: Depression and the risk for cardiovascular diseases: systematic review and meta-analysis. Int J Geriatr Psychiatry 2007;22:613-626.
Markowitz S, Friedman MA, Arent SM: Understanding the relation between obesity and depression: causal mechanisms and implications for treatment. Clin Psychol Sci Pract 2008;15:1-20.
Friedman MA, Brownell KD: Psychological consequences of obesity. In: Fairburn CG, Brownell KD (eds); Eating disorders and obesity A comprehensive handbook. Guilford Press: New York 2002, pp 50-61.
Forman-Hoffman VL, Yankey JW, Hillis SL, Wallace RB, Wolinsky FD: Weight and depressive symptoms in older adults: direction of influence? J Gerontol B Psychol Sci Soc Sci 2007;1:S43-51.
Bouwman V, Adriaanse MC, van 't Riet E, Snoek FJ, Dekker JM, Nijpels G: Depression, anxiety and glucose metabolism in the general dutch population: the new Hoorn study. PLoS One 2010;5:e9971.
Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG: Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 2010;67:220-9.
Preiss K, Brennan L, Clarke D: Obesity Reviews 2013;14:906-918.
Faith MS, Butryn M, Wadden TA, Fabricatore A, Nguyen AM, Heymsfield SB: Evidence for prospective associations among depression and obesity in population-based studies. Obes Rev 2011;12:e438-e453.
Gois C, Akiskal H, Akiskal K, Figueira ML: The relationship between temperament, diabetes and depression. J Affect Disord 2012;142:67-71.
BeLue R, Francis LA, Colaco B: Mental health problems and overweight in a nationally representative sample of adolescents: effects of race and ethnicity. Pediatrics 2009;123:697-702.
Cooke L, Wardle J: Depression and obesity. Depression and physical illness. Cambridge University Press: New York 2007, pp 238.
Onyike CU, Crum RM, Lee HB, Lyketsos CG, Eaton WW: Is obesity associated with major depression? Results from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 2003;158:1139-1147.
Schweinfurth N, Borgwardt S, Walter M, Lang UE: Depression and Obesity. In Obesity. Page
Flórez KR, Dubowitz T, Ghosh-Dastidar MB, Beckman R, Collins RL: Associations between Depressive Symptomatology, Diet, and Body Mass Index among Participants in the Supplemental Nutrition Assistance Program. J Acad Nutr Diet 2015;115:1102-1108.
Opie RS, O'Neil A, Itsiopoulos C, Jacka FN: The impact of whole-of-diet interventions on depression and anxiety: a systematic review of randomised controlled trials. Public Health Nutr 2015;18:2074-2093.
Pyndt Jørgensen B, Hansen JT, Krych L, Larsen C, Klein AB, Nielsen DS, Josefsen K, Hansen AK, Sørensen DB: A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice. PLoS One 2014;9:e103398.
Zhou L, Foster JA: Psychobiotics and the gut-brain axis: in the pursuit of happiness. Neuropsychiatr Dis Treat 2015;11:715-723.
Homan P, Grob S, Milos G, Schnyder U, Eckert A, Lang U, Hasler G: The role of BDNF, leptin, and catecholamines in reward learning in bulimia nervosa. Int J Neuropsychopharmacol 2014;18:5.
Becker C, Zeau B, Rivat C, Blugeot A, Hamon M, Benoliel JJ: Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin. Mol Psychiatry 2008;13:1079-1092.
Roesler R, Henriques JA, Schwartsmann G: Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders. CNS Neurol Disord Drug Targets 2006;5:197-204.
Kuo LE, Kitlinska JB, Tilan JU, Kvetnanský R, Zukowska Z: "Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome". Nat Med 2007;13:803-811.
Ströhle A, Romeo E, di Michele F, Pasini A, Hermann B, Gajewsky G, Holsboer F, Rupprecht R: Induced panic attacks shift gamma-aminobutyric acid type A receptor modulatory neuroactive steroid composition in patients with panic disorder: preliminary results. Arch Gen Psychiatry 2003;60:161-168.
Arey RN, Enwright JF 3rd, Spencer SM, Falcon E, Ozburn AR, Ghose S, Tamminga C, McClung CA: An important role for Cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors.Mol Psychiatry 2014;19:342-350.
Mason BL, Lobo MK, Parada LF. Lutter M: Trk B signaling in dopamine 1 receptor neurons regulates food intake and body weight. Obesity (Silver Spring) 2013;21:2372-2376.
Ricken R, Adli M, Lange C, Krusche E, Stamm TJ, Gaus S, Koehler S, Nase S, Bschor T, Richter C, Steinacher B, Heinz A, Rapp MA, Borgwardt S, Hellweg R, Lang UE: Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants. J Clin Psychopharmacol 2013;33:806-809.
Lang UE, Hellweg R, Kalus P, Bajbouj M, Lenzen KP, Sander T, Kunz D, Gallinat J: Association of a functional BDNF polymorphism and anxiety-related personality traits. Psychopharmacology (Berl) 2005;180:95-99.
Lang UE, Hellweg R, Gallinat J: BDNF serum concentrations in healthy volunteers are associated with depression-related personality traits. Neuropsychopharmacology 2004;29:795-798.
Morales-Medina JC, Dumont Y, Quirion R: A possible role of neuropeptide Y in depression and stress. Brain Res 2010;1314:194-205.
Gallinat J, Schubert F, Brühl R, Hellweg R, Klär AA, Kehrer C, Wirth C, Sander T, Lang UE: Met carriers of BDNF Val66Met genotype show increased N-acetylaspartate concentration in the anterior cingulate cortex. Neuroimage 2010;49:767-771.
Lang UE, Bajbouj M, Gallinat J, Hellweg R: Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation. Psychopharmacology 2006;187:56-59.
Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH: Ghrelin Mol Metab 2015;4:437-460.
Schellekens H, Finger BC, Dinan TG, Cryan JF: Ghrelin signaling and obesity: at the interface of stress, mood and food reward. Pharmacol Ther 2012;135:316-326.
Lutter M, Nestler EJ: Homeostatic and hedonic signals interact in the regulation of food intake. J Nutr 2009;139:629-632.
Kluge M, Schüssler P, Dresler M, Schmidt D, Yassouridis A, Uhr M, Steiger A: Effects of ghrelin on psychopathology, sleep and secretion of cortisol and growth hormone in patients with major depression. J Psychiatr Res 2011;45:421-426.
Lutter M, Sakata I, Osborne-Lawrence S, Rovinsky SA, Anderson JG, Jung S, Birnbaum S, Yanagisawa M, Elmquist JK, Nestler EJ, Zigman JM: The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci 2008;11:752-753.
Vasselli JR, Scarpace PJ, Harris RB, Banks WA: Dietary components in the development of leptin resistance. Adv Nutr 2013;4:164-175.
Häfner S, Baumert J, Emeny RT, Lacruz ME, Bidlingmaier M, Reincke M, Ladwig KH: Sleep disturbances and depressed mood: a harmful combination associated with increased leptin levels in women with normal weight. Biol Psychol 2012;89:163-169.
Garza JC, Guo M, Zhang W, Lu XY: Leptin restores adult hippocampal neurogenesis in a chronic unpredictable stress model of depression and reverses glucocorticoid-induced inhibition of GSK-3β/β-catenin signaling. Mol Psychiatry 2012;17:790-808.
Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, Maratos-Flier E, Flier JS: Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 2006;51:811-822.
Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, Thurmon JJ, Marinelli M, DiLeone RJ: Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 2006;51:801-810.
Engeli L, Delahaye M, Borgwardt S, Gallinat J, Müller D, Walter M, Lang UE, Beck J: Akt2 Gene is Associated with Anxiety and Neuroticism in Humans. J Vasc Med Surg 2014;2:3. doi: 10.4172/2329-6925.1000141.
Ackermann TF, Hörtnagl H, Wolfer DP, Colacicco G, Sohr R, Lang F, Hellweg R, Lang UE: Phosphatidylinositide dependent kinase deficiency increases anxiety and decreases GABA and serotonin abundance in the amygdala. Cell Physiol Biochem 2008;22:735-744.
Ackermann TF, Kempe DS, Lang F, Lang UE: Hyperactivity and enhanced curiosity of mice expressing PKB/SGK-resistant glycogen synthase kinase-3 (GSK-3). Cell Physiol Biochem 2010;25:775-786.
Leibrock C, Ackermann TF, Hierlmeier M, Lang F, Borgwardt S, Lang UE: Akt2 deficiency is associated with anxiety and depressive behavior in mice. Cell Physiol Biochem 2013;32:766-777.
Anderson MF, Aberg MA, Nilsson M, Eriksson PS: Insulin-like growth factor-I and neurogenesis in the adult mammalian brain. Brain Res Dev Brain Res 2002;134:115-122.
Hoshaw BA, Hill TI, Crowley JJ, Malberg JE, Khawaja X, Rosenzweig-Lipson S, Schechter LE, Lucki I: Antidepressant-like behavioral effects of IGF-I produced by enhanced serotonin transmission. Eur J Pharmacol 2008;594:109-116.
Cline BH, Steinbusch HW, Malin D, Revishchin AV, Pavlova GV, Cespuglio R, Strekalova T: The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2. BMC Neurosci 2012;13:110.
Malberg JE, Platt B, Rizzo SJ, Ring RH, Lucki I, Schechter LE, Rosenzweig-Lipson S: Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects. Neuropsychopharmacology 2007;32:2360-2368.
Aberg MA, Aberg ND, Hedbacker H, Oscarsson J, Eriksson PS: Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 2000;20:2896-2903.
Grunbaum-Novak N, Taler M, Gil-Ad I, Weizman A, Cohen H, Weizman R: Relationship between antidepressants and IGF-1 system in the brain: possible role in cognition. Eur Neuropsychopharmacol 2008;18:431-438.
Paslakis G1, Blum WF, Deuschle M: Intranasal insulin-like growth factor I (IGF-I) as a plausible future treatment of depression. Med Hypotheses 2012;79:222-225.
Marano CM, Workman CI, Lyman CH, Kramer E, Hermann CR, Ma Y, Dhawan V, Chaly T, Eidelberg D, Smith GS: The relationship between fasting serum glucose and cerebral glucose metabolism in late-life depression and normal aging. Psychiatry Res 2014;222:84-90.
Wexler DJ, Porneala B, Chang Y, Huang ES, Huffman JC, Grant RW: Diabetes differentially affects depression and self-rated health by age in the US. Diabetes Care 2012;35:1575-1577.
Gold SM, Dziobek I, Sweat V, Tirsi A, Rogers K, Bruehl H, Tsui W, Richardson S, Javier E, Convit A: Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia 2007;50:711-719.
Convit A, Wolf OT, Tarshish C, de Leon MJ: Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly. Proc Natl Acad Sci U S A 2003;100:2019-2022.
Wölnerhanssen BK, Meyer-Gerspach AC, Schmidt A, Zimak N, Peterli R, Beglinger C, Borgwardt S: Dissociable Behavioral, Physiological and Neural Effects of Acute Glucose and Fructose Ingestion: A Pilot Study. PLoS One 2015;10:e0130280.
Vlassara H, Striker GE: AGE restriction in diabetes mellitus: a paradigm shift. Nat Rev Endocrinol 2011;7:526-539.
Kilhovd BK, Juutilainen A, Lehto S, Rönnemaa T, Torjesen PA, Hanssen KF, Laakso M: Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study. Diabetologia 2007;50:1409-1417.
Tan KC, Chow WS, Ai VH, Metz C, Bucala R, Lam KS: Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care 2002;25:1055-1059.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL: A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446-457.
Stelzhammer V, Haenisch F, Chan MK, Cooper JD, Steiner J, Steeb H, Martins-de-Souza D, Rahmoune H, Guest PC, Bahn S: Proteomic changes in serum of first onset, antidepressant drug-naïve major depression patients. Int J Neuropsychopharmacol 2014;17:1599-608.
Bandaru SS, Lin K, Roming SL, Vellipuram R, Harney JP: Effects of PI3K inhibition and low docosahexaenoic acid on cognition and behavior. Physiol Behav 2010;100: 239-244.
Neufeld KM, Kang N, Bienenstock J, Foster JA: Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 2011;23:255-264.
Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF: Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 2011;108:16050-16055.
Scott LV, Clarke G, Dinan TG: The brain-gut axis: a target for treating stress-related disorders. Mod Trends Pharmacopsychiatri 2013;28:90-99.
Cryan JF, Dinan TG: Mind-altering microorganisms: the impact of the gut microbiota on brain and behavior. Nat Rev Neurosci 2012;13:701-712.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ: Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505:559-563.
Leclercq S, Matamoros S, Neyrinck AM, Jamar F, Stärkel P, Windey K, Tremaroli V, Bäckhed F, Verbeke K, de Timary P, Delzenne NM: Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci U S A 2014;111:E4485-4493.
Naseribafrouei A, Hestad K, Avershina E, Sekelja M, Linløkken A, Wilson R, Rudi K: Correlation between the human fecal microbiota and depression. Neurogastroenterol Motil 2014;26:1155-1162.
Logan AC, Katzman M: Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses 2005;64:533-538.
Luna-RA, Foster JA: Gut brain axis: diet microbiota interactions and implications for modulation of anxiety and depression. Curr Opin Biotechnol 2015;32:5-41.
Mayer EA, Tillisch K, Gupta A: Gut/brain axis and the microbiota. J Clin Invest 2015;125:926-938.
Rao AV, Bested AC, Beaulne TM, Katzman MA, Iorio C, Berardi JM, Logan AC: A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog 2009;1:6.
Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM: Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 2011;105:755-764.
Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PW: Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl) 2015;232:1793-801.
Ruusunen A, Lehto SM, Mursu J, Tolmunen T, Tuomainen TP, Kauhanen J, Voutilainen S: Dietary patterns are associated with the prevalence of elevated depressive symptoms and the risk of getting a hospital discharge diagnosis of depression in middle-aged or older Finnish men. J Affect Disord 2014;159:1-6.
Nanri A, Eguchi M, Kuwahara K, Kochi T, Kurotani K, Ito R, Pham NM, Tsuruoka H, Akter S, Jacka F, Mizoue T, Kabe I: Macronutrient intake and depressive symptoms among Japanese male workers: the Furukawa Nutrition and Health Study. Psychiatry Res 2014;220:263-268.
Jacka FN, Rothon C, Taylor S, Berk M, Stansfeld SA: Diet quality and mental health problems in adolescents from East London: a prospective study. Soc Psychiatry Psychiatr Epidemiol. 2013;48:1297-1306.
Chan R, Chan D, Woo J: A Prospective Cohort Study to Examine the Association between Dietary Patterns and Depressive Symptoms in Older Chinese People in Hong Kong. PLoS One 2014;9:e105760.
Opie RS, O'Neil A, Itsiopoulos C, Jacka FN: The impact of whole-of-diet interventions on depression and anxiety: a systematic review of randomised controlled trials. Public Health Nutr 2015;18:2074-93.
Pyndt Jørgensen B, Hansen JT, Krych L, Larsen C, Klein AB, Nielsen DS, Josefsen K, Hansen AK, Sørensen DB: A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice. PLoS One 2014;9:e103398.
Zhou L, Foster JA: Psychobiotics and the gut-brain axis: in the pursuit of happiness. Neuropsychiatr Dis Treat 2015;11:715-23.
Knight A, Bryan J, Wilson C, Hodgon J, Murphy K: A randomised controlled intervention trial evaluating the efficacy of a Mediterranean dietary pattern on cognitive function and psychological wellbeing in healthy older adults: the MedLey study. BMC Geriatrics 2015;15:55.
Dipnall JF, Pasco JA, Meyer D, Berk M, Williams LJ, Dodd S, Jacka FN. The association between dietary patterns, diabetes and depression. J Affect Disord 2015;174:215-24.
Sánchez-Villegas A, Martínez-González MA, Estruch R, Salas-Salvadó J, Corella D, Covas MI, Arós F, Romaguera D, Gómez-Gracia E, Lapetra J, Pintó X, Martínez JA, Lamuela-Raventós RM, Ros E, Gea A, Wärnberg J, Serra-Majem L: Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med 2013;11:208.
Psaltopoulou T, Sergentanis TN, Panagiotakos DB, Sergentanis IN, Kosti R, Scarmeas N: Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis. Ann Neurol 2013;74:580-591.
Agarwal U, Mishra S, Xu J, Levin S, Gonzales J, Barnard ND: A multicenter randomized controlled trial of a nutrition intervention program in a multiethnic adult population in the corporate setting reduces depression and anxiety and improves quality of life: the GEICO study. Am J Health Promot 2015;29:245-254.
Akhondzadeh S, Gerbarg PL, Brown RP: Nutrients for prevention and treatment of mental health disorders. Psychiatr Clin North Am 2013;36:25-36.
Beezhold BL, Johnston CS, Daigle DR: Vegetarian diets are associated with healthy mood states: a crosssectional study in Seventh Day Adventist adults. Nutr J 2010;9:26.
Beezhold BL, Johnston CS: Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial. Nutrition J 2012;11:9.
Surwit RS, Feinglos MN, McCaskill CC, Clay SL, Babyak MA, Brownlow BS, Plaisted CS, Lin PH: Metabolic and behavioral effects of a high-sucrose diet during weight loss. Am J Clin Nutr 1997;65:908-915.
Gangwisch JE, Hale L, Garcia L, Malaspina D, Opler MG, Payne ME, Rossom RC, Lane D: High glycemic index diet as a risk factor for depression: analyses from the Women's Health Initiative. Am J Clin Nutr 2015; 102:454-463.
Stahl ST, Albert SM, Dew MA, Lockovich MH, Reynolds CF 3rd: Coaching in healthy dietary practices in at-risk older adults: a case of indicated depression prevention. Am J Psychiatry 2014;171:499-505.
Reynolds CF 3rd, Cuijpers P, Patel V, Cohen A, Dias A, Chowdhary N, Okereke OI, Dew MA, Anderson SJ, Mazumdar S, Lotrich F, Albert SM: ReynoldsEarly intervention to reduce the global health and economic burden of major depression in older adults. Annu Rev Public Health 2012;33:123-35.
Perez-Cornago A, de la Iglesia R, Lopez-Legarrea P, Abete I, Navas-Carretero S, Lacunza CI, Lahortiga F, Martinez-Gonzalez MA, Martinez JA, Zulet MA: A decline in inflammation is associated with less depressive symptoms after a dietary intervention in metabolic syndrome patients: a longitudinal study. Nutr J 2014;24:13-36.
Ciarambino T, Castellino P, Paolisso G, Coppola L, Ferrara N, Signoriello G, Giordano M: Long term effects of low protein diet on depressive symptoms and quality of life in elderly Type 2 diabetic patients. Clin Nephrol 2012;78: 122-8.
Miki T, Kochi T, Eguchi M, Kuwahara K, Tsuruoka H, Kurotani K, Ito R, Akter S, Kashino I, Pham NM, Kabe I, Kawakami N, Mizoue T, Nanri A: Dietary intake of minerals in relation to depressive symptoms in Japanese employees: the Furukawa Nutrition and Health Study. Nutrition 2015;31:686-690.
Vashum KP, McEvoy M, Milton AH, McElduff P, Hure A, Byles J, Attia J: Dietary zinc is associated with a lower incidence of depression: findings from two Australian cohorts. J Affect Disord 2014;166:249-257.
Sawada T, Yokoi K: Effect of zinc supplementation on mood states in young women: a pilot study. Eur J Clin Nutr. 2010;64:331-333.
Ghafari M, Whittle N, Miklósi AG, Kotlowsky C, Schmuckermair C, Berger J, Bennett KL, Singewald N, Lubec G: Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice. Brain Struct Funct 2015;220:2209-2221.
Deutschenbaur L, Beck J, Kiyhankhadiv A, Mühlhauser M, Borgwardt S, Walter M, Hasler G, Sollberger D, Lang UE: Role of calcium, glutamate and NMDA in major depression and therapeutic application. Prog Neuropsychopharmacol Biol Psychiatry 2015;pii:S0278-5846(15)00049-4. doi: 10.1016/j.pnpbp.2015.02.015.
Pochwat B, Pałucha-Poniewiera A, Szewczyk B, Pilc A, Nowak G: NMDA antagonists under investigation for the treatment of major depressive disorder. Expert Opin Investig Drugs 2014;23:1181-1192.
Murck H: Ketamine, magnesium and major depression-from pharmacology to pathophysiology and back. J Psychiatr Res 2013;47:955-965.
Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F: Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnes Res 2008;21:218-223.
Eby GA 3rd, Eby KL: Magnesium for treatment-resistant depression: a review and hypothesis. Med Hypotheses 2010;74:649-660.
Panagiotakos DB, Mamplekou E, Pitsavos C, Kalogeropoulos N, Kastorini CM, Papageorgiou C, Papadimitriou GN, Stefanadis C: Fatty acids intake and depressive symptomatology in a Greek sample: an epidemiological analysis. J Am Coll Nutr 2010;29:586-594.
Park Y, Park YS, Kim SH, Oh DH, Park YC: Supplementation of n-3 Polyunsaturated Fatty Acids for Major Depressive Disorder: A Randomized, Double-Blind, 12-Week, Placebo-Controlled Trial in Korea. Ann Nutr Metab 2015;66:141-148.
Yoshikawa E, Nishi D, Matsuoka Y: Fish consumption and resilience to depression in Japanese company workers: a cross-sectional study. Lipids Health Dis 2015;14:51.
Bloch MH, Hannestad J: Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry 2012;17:1272-1282.
Fares H, Lavie CJ, DiNicolantonio JJ, O'Keefe JH, Milani RV: Omega-3 fatty acids: a growing ocean of choices. Curr Atheroscler Rep 2014;16:389.
Saxholt E, Christensen AT, Møller A: Danish Food Composition Databank, Revision 7. Søborg, Denmark: Department of Nutrition, National Food Institute, Technical University of Denmark; 2009.
Smith KJ, Sanderson K, McNaughton SA, Gall SL, Dwyer T, Venn AJ: Longitudinal associations between fish consumption and depression in young adults. Am J Epidemiol 2014;179:1228-1235.
McLean A, Rubinsztein JS, Robbins TW, Sahakian BJ: The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression. Psychopharmacology (Berl) 2004;171:286-297.
Davis JD, Tremont G: Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol 2007;32:49-65.
Frey A, Lampert A, Dietz K, Striebich S, Locher C, Fedorenko O, Möhle R, Gallinat J, Lang F, Lang UE: Thyrotropin serum concentrations in healthy volunteers are associated with depression-related personality traits. Neuropsychobiology 2007;56:123-6.
McCarty MF: Longevity effect of chromium picolinate - ‘rejuvenation' of hypothalamic function? Med Hypotheses 1994;43:253-265.
McLeod MN, Gaynes BN, Golden RN: Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psychiatry 1999;60:237-240.
McLeod MN, Golden RN: Chromium treatment of depression. Int J Neuropsychopharmacol 2000;3:311-314.
Davidson JR, Abraham K, Connor KM, McLeod MN: Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-264.
Prohan M, Amani R, Nematpour S, Jomehzadeh N, Haghighizadeh MH: Total antioxidant capacity of diet and serum, dietary antioxidant vitamins intake, and serum hs-CRP levels in relation to depression scales in university male students. Redox Rep 2014;19:133-139.
Naylor GJ, Smith AH: Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med 1981;11:249-256.
Kay DS, Naylor GJ, Smith AH, Greenwood C: The therapeutic effect of ascorbic acid and EDTA in manic-depressive psychosis: double-blind comparisons with standard treatments. Psychol Med 1984;14:533-539.
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.
Reynolds EH: Folic acid, ageing, depression, and dementia. BMJ 2002;324:1512-1515.
Mischoulon D, Raab MF: The role of folate in depression and dementia. J Clin Psychiatry 2007;68:28-33.
Almeida OP, Ford AH, Flicker L: Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. Int Psychogeriatr 2015;27:727-737.
Almeida OP, Marsh K, Alfonso H, Flicker L, Davis TM, Hankey GJ: B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Ann Neurol 2010;68:503-510.
Lazarou C, Kapsou M: The role of folic acid in prevention and treatment of depression: an overview of existing evidence and implications for practice. Complement Ther Clin Pract 2010;16:161-166.
Sharpley AL, Hockney R, McPeake L, Geddes JR, Cowen PJ: Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial. J Affect Disord 2014;167:306-311.
Miyake Y, Tanaka K, Okubo H, Sasaki S, Arakawa M: Intake of dairy products and calcium and prevalence of depressive symptoms during pregnancy in Japan: a cross-sectional study. BJOG 2015;122:336-43.
Shonesy BC, Jalan-Sakrikar N, Cavener VS, Colbran RJ: CaMKII: a molecular substrate for synaptic plasticity and memory. Prog Mol Biol Transl Sci 2014;122:61-87.
Szegedi V, Juhász G, Zhang X, Barkóczi B, Qi H, Madeira A, Kapus G, Svenningsson P, Spedding M, Penke B: Tianeptine potentiates AMPA receptors by activating CaMKII and PKA via the p38, p42/44 MAPK and JNK pathways. Neurochem Int 2011;59:1109-1122.
Bertone-Johnson ER, Hankinson SE, Forger NG, Powers SI, Willett WC, Johnson SR, Manson JE: Plasma 25-hydroxyvitamin D and risk of premenstrual syndrome in a prospective cohort study. BMC Womens Health 2014;14:56.
Ubbenhorst A, Striebich S, Lang F, Lang UE: Exploring the relationship between vitamin D and basic personality traits.Psychopharmacology (Berl) 2011;215:733-737.
Hoang MT, Defina LF, Willis BL: Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults: the Cooper Center longitudinal study. Mayo Clin Proc 2011;86:1050-1055.
Dumville JC, Miles JN, Porthouse J, Cockayne S, Saxon L, King C: Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. J Nutr Health Aging 2006;10:151-153.
Malkesman O, Austin DR, Tragon T, Wang G, Rompala G, Hamidi AB, Cui Z, Young WS, Nakazawa K, Zarate CA, Manji HK, Chen G: Acute D-serine treatment produces antidepressant-like effects in rodents. Int J Neuropsychopharmacol 2012;15:1135-1148.
Otte DM, Barcena de Arellano ML, Bilkei-Gorzo A, Albayram O, Imbeault S, Jeung H, Alferink J, Zimmer A: Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior. PLoS One 2013;8:e67131.
Widmer RJ, Flammer AJ, Lerman LO, Lerman A: The Mediterranean diet, its components, and cardiovascular disease. Am J Med 2015;128:229-238.
Serrano Ripoll MJ, Oliván-Blázquez B, Vicens-Pons E, Roca M, Gili M, Leiva A, García-Campayo J, Demarzo MP, García-Toro M: Lifestyle change recommendations in major depression: Do they work? J Affect Disord 2015;183:221-228.
Zeinoddini A, Sorayani M, Hassanzadeh E, Arbabi M, Farokhnia M, Salimi S, Ghaleiha A, Akhondzadeh S: Pioglitazone adjunctive therapy for depressive episode of bipolar disorder: a randomized, double-blind, placebo-controlled trial. Depress Anxiety 2015;32:167-173.
Salehi-Sadaghiani M, Javadi-Paydar M, Gharedaghi MH, Zandieh A, Heydarpour P, Yousefzadeh-Fard Y, Dehpour AR: NMDA receptor involvement in antidepressant-like effect of pioglitazone in the forced swimming test in mice. Psychopharmacology (Berl) 2012;223:345-355.
Rondanelli M, Opizzi A, Solerte SB, Trotti R, Klersy C, Cazzola R: Administration of a dietary supplement (Noleyl-phosphatidylethanolamine and epigallocatechin-3-gallate formula) enhances compliance with diet in healthy overweight subjects: a randomized controlled trial. Br J Nutr 2009;101:457-464.
Borgwardt S, Hammann F, Scheffler K, Kreuter M, Drewe J, Beglinger C: Neural effects of green tea extract on dorsolateral prefrontal cortex. Eur J Clin Nutr 2012;66:1187-1192.
Schmidt A, Hammann F, Wölnerhanssen B, Meyer-Gerspach AC, Drewe J, Beglinger C, Borgwardt S: Green tea extract enhances parieto-frontal connectivity during working memory processing. Psychopharmacology (Berl) 2014;231:3879-3888.
Sepanjnia K, Modabbernia A, Ashrafi M, Modabbernia MJ, Akhondzadeh S: Pioglitazone adjunctive therapy for moderate-to-severe major depressive disorder: randomized double-blind placebo-controlled trial. Neuropsychopharmacology 2012;37:2093-100.
Guo M, Mi J, Jiang QM, Xu JM, Tang YY, Tian G, Wang B: Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus. Clin Exp Pharmacol Physiol 2014;41:650-656.
Stafford L, Berk M: The use of statins after a cardiac intervention is associated with reduced risk of subsequent depression: proof of concept for the inflammatory and oxidative hypotheses of depression? J Clin Psychiatry 2011;72:1229-1235.
Haghighi M, Khodakarami S, Jahangard L, Ahmadpanah M, Bajoghli H, Holsboer-Trachsler E, Brand S: In a randomized, double-blind clinical trial, adjuvant atorvastatin improved symptoms of depression and blood lipid values in patients suffering from severe major depressive disorder. J Psychiatr Res 2014;58:109-114.
Grant P, Lipscomb D, Quin J: Psychological and quality of life changes in patients using GLP-1 analogues. J Diabetes Complications 2011;25: 244-246.
Gárate I, Garcia-Bueno B, Madrigal JL, Caso JR, Alou L, Gomez-Lus ML, Micó JA, Leza JC: Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway. Biol Psychiatry 2013;73:32-43.
Open Access License / Drug Dosage / Disclaimer
Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (, applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.