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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Geographic areas where consumption of DHA is high are associated with decreased rates of depression. DHA deficiency states, such as alcoholism and the postpartum period, also are linked with depression. Individuals with major depression have marked depletions in omega-3 FAs (especially DHA) in erythrocyte phospholipids compared with controls. These data suggest that DHA may be associated with depression, and the limited data available on supplementation with DHA or other omega-3 FAs seem to support the hypothesis that DHA may have psychotropic effects. Overall, the use of EFAs is promising, particularly in view of the many illnesses potentially treatable with these substances; however, larger, carefully designed studies are needed to establish whether DHA is an effective and safe antidepressant, mood stabilizer, or antipsychotic. A few preliminary trials of DHA are in progress, but no studies comparing DHA against placebo or against an established antidepressant have been carried out. Studies to address this issue are being developed at the Massachusetts General Hospital. Studies likely will require escalating doses of DHA, eventually reaching high levels so as to ensure that patients will avoid a potentially ineffective subclinical dose. Careful monitoring of dietary intake among subjects also will necessary because a high intake of omega-3-rich foods may confound results. Finally, large-scale, placebo-controlled, double-blind trials comparing the efficacy and safety of DHA against standard antidepressants are required before psychiatrists can recommend DHA therapy as effective and safe for the treatment of depression and other mood disorders. Given the popularity of self-medication by patients who already are taking marketed antidepressants, studies examining the use of DHA as an augmentor to standard antidepressants may answer whether DHA can occupy a niche as an augmenting agent for patients who have made a partial response or have not responded to conventional antidepressants. Considering that natural medications generally seem best for treating mild to moderate illness, the role of DHA as a therapy for minor and subsyndromal depression also should be considered. It is hoped that studies of these types will help to clarify some of the knowledge gaps outlined in this article.
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PMID:Docosahexanoic acid and omega-3 fatty acids in depression. 1114 47

The effects of a 1% addition of cholesterol to a diet low in EFA on FA desaturases were examined. The administration of cholesterol markedly increased the esterified cholesterol content in microsomes and total liver lipids from the first day, whereas the proportion of free cholesterol remained unaltered throughout the treatment. An excellent homeostasis in the free cholesterol content was apparently evoked by the acyl-CoA cholesterol acyltransferase. The cholesterol esters were mainly oleate, palmitate, and stearate, and the addition of cholesterol increased the relative proportions of cholesterol palmitoleate and oleate. The addition of cholesterol to a low-EFA diet induced, as in animals fed a high-EFA diet, a marked increase in liver stearoyl-CoA desaturase-1 mRNA and enzyme activity. This increased activity apparently evoked a similar enhancement of palmitoleic and oleic acids in total and microsomal liver lipids. The cholesterol-rich diet depressed the liver A6 and delta5 desaturase activity. However, the abundance of delta6 desaturase mRNA was not modified throughout the treatment. This indicates that the depressive effect is evoked at a step beyond that controlled by the mRNA level. The depression of both enzymatic activities was consistent with the decrease in the percentages of arachidonic acid and DHA in total and microsomal liver lipids. Taken together, these results indicate that through its modulating effect on the desaturases, dietary cholesterol may lead an animal or human fed low-EFA diet to a true deficiency by the decreased synthesis of the highly polyunsaturated acids derived from linoleic and alpha-linolenic acids.
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PMID:Dietary cholesterol modulates delta6 and delta9 desaturase mRNAs and enzymatic activity in rats fed a low-eFA diet. 1203 Mar 18

Bipolar disorder (BD) is characterized by periods of abnormally elevated mood (mania) that cycle with abnormally lowered mood (depression). Multiple structural, metabolic, and biochemical abnormalities are evident in the brain's cortex, subcortex, and deeper regions. This disorder is highly genetically conditioned but also highly susceptible to environmental stressors: prenatal or perinatal insults, childhood sexual or physical abuse, challenging life events, substance abuse, and other toxic chemical exposures. Its high morbidity, lost productivity, and suicide risk place a great toll on society. Since World War II, BD has been steadily worsening with earlier age of onset, greater intensity of symptoms, and development of drug resistance. Incidence in children is rising and misdiagnosis is common. Disciplined management of the many risk factors is essential, including cognitive psychotherapy and support from family and community. Lithium has been the foundational treatment, followed by valproate and other mood stabilizers, antidepressants, and anticonvulsants. Several single-nutrient and multinutrient supplements have also proven beneficial. Controlled, double-blind trials show multinutrient combinations of vitamins, minerals, orthomolecules, herbals, and the omega-3 fatty acids EPA and DHA to be effective monotherapy. The molecular action of lithium and valproate converge with nutrients on the level of the cell membrane and its molecular signal transduction systems. This emergent, unified rationale presages effective integrative management of bipolar disorder.
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PMID:Bipolar disorder and cell membrane dysfunction. Progress toward integrative management. 1525 74

Omega-3 PUFA of marine origin reduce adiposity in animals fed a high-fat diet. Our aim was to learn whether EPA and DHA could limit development of obesity and reduce cellularity of adipose tissue and whether other dietary FA could influence the effect of EPA/DHA. Weight gain induced by composite high-fat diet in C57BL/6J mice was limited when the content of EPA/DHA was increased from 1 to 12% (wt/wt) of dietary lipids. Accumulation of adipose tissue was reduced, especially of the epididymal fat. Low ratio of EPA to DHA promoted the effect. A higher dose of EPA/DHA was required to reduce adiposity when admixed to diets that did not promote obesity, the semisynthetic high-fat diets rich in EFA, either alpha-linolenic acid (ALA, 18:3 n-3, the precursor of EPA and DHA) or linoleic (18:2 n-6) acid. Quantification of adipose tissue DNA revealed that except for the diet rich in ALA the reduction of epididymal fat was associated with 34-50% depression of tissue cellularity, similar to the 30% caloric restriction in the case of the high-fat composite diet. Changes in plasma markers and adipose gene expression indicated improvement of lipid and glucose metabolism due to EPA/DHA even in the context of the diet rich in ALA. Our results document augmentation of the antiadipogenic effect of EPA/DHA during development of obesity and suggest that EPA/DHA could reduce accumulation of body fat by limiting both hypertrophy and hyperplasia of fat cells. Increased dietary intake of EPA/DHA may be beneficial regardless of the ALA intake.
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PMID:Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. 1573 13

Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are the major polyunsaturated fatty acids in the membranes of brain and retinal cells. Animals specifically deficient in dietary n-3 fatty acids have low DHA content in their membranes, reduced visual acuity and impaired learning ability. Studies on bottle-fed human infants have shown that adding DHA and AA to milk replacer-formulas can bring their concentrations in the infant blood lipids to values as high as those produced by breast-feeding and significantly improves mental development and maturation of visual function. In older subjects, diverse neuropsychiatric and neurodegenerative diseases have been associated to decreased blood levels of n-3 PUFA. Low intakes of fish or of n-3 PUFA in populations have been associated with increased risks of depression and Alzheimer disease, and n-3 PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3), have shown efficacy as adjunctive treatment - and in some cases as the only treatment--in several psychiatric disorders. The mechanisms by which polyunsaturated fatty acids have an impact on neuronal functions will be reviewed: the modulation of membrane biophysical properties, regulation of neurotransmitter release, synthesis of biologically active oxygenated derivatives, and nuclear receptor-mediated transcription of genes responsive to fatty acids or to their derivatives.
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PMID:Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. 1576 97

Omega-3 polyunsaturated fatty acids have two major field of interest. The first lies in their quantitative abundance and their role in the development and maintenance of the brain. The second is their role in the prevention of different pathologies, mainly the cardiovascular diseases, and more lately some psychiatric disorders, from stress to depression and dementia. Thus, dietary omega-3 fatty acids are very important to ensure brain structure and function, more specifically during development and aging. However, concerning essential alpha-linolenic acid (ALA), most occidental diets contain about 50 % of the recommended dietary allowances. The problem is to know which foods are naturally rich in this fatty acid, and to determine the true impact of the formulations (enriched in omega-3 fatty acids, either ALA or EPA and DHA) in chows used on farms and breeding centres on the nutritional value of the products (meat, butter, milk and dairy products, cheese, and eggs, etc), and thus their effect on the health of consumers, especially to ensure adequate quantities in the diet of the aging people. The consequences (qualitative and quantitative) of modifications in the composition of animal foods on the value of derived products consumed by humans are more marked when single-stomach animals are concerned than multi-stomach animals. Because, for example, hydrogenating intestinal bacteria of the latter group transform a large proportion of polyunsaturated fatty acids in their food into saturated fatty acids, among others, thus depriving them of any biological interest. Under the best conditions, by feeding animals with extracts of linseed and rapeseed grains for example, the level of ALA acid is increased approximately two-fold in beef and six-fold in pork, ten-fold in chicken, and forty-fold in eggs. By feeding animals with fish extracts or algae (oils) the level of DHA is increased about 2-fold in beef, 7-fold in chicken, 6-fold in eggs, and 20-fold in fish (salmon). To obtain such results, it is sufficient to respect only the physiological needs of the animal, which was generally the case with traditional methods. It is important to stress the role of fish, whose nutritional value for humans in terms of lipids (determined by omega-3 fatty acid levels) can vary considerably according to the type of fats the animals have been fed. The aim of preventing some aspects of cardiovascular disease (and other pathologies) can be achieved, or on the contrary frustrated, depending on the nature of fatty acids present in fish flesh, the direct consequence of the nature of fats with which they have been fed. It is the same for eggs, "omega- 3 eggs" being in fact similar to natural eggs, were used in the formulation of certain formula milks for infants, whose composition was closest to that of breast milk. In fact, the additional cost on the price paid by the consumer is modest compared to the considerable gain in nutritional value in terms of omega-3 fatty acids content. Interestingly, in aged people, ALA recommendations in France are increased (0.8% daily energy intake in adult, 0.9 % in aged) and DHA is multiplied by 2 (0.05 % daily energy intake in adult, 0.1 % in aged; as well as in pregnant and lactating women).
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PMID:Where to find omega-3 fatty acids and how feeding animals with diet enriched in omega-3 fatty acids to increase nutritional value of derived products for human: what is actually useful ? 1598 Sep 24

In contrast to other tissues, the nervous system is enriched in the polyunsaturated fatty acids (PUFAs): arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3). Despite their abundance in the nervous system, AA and DHA cannot be synthesized de novo by mammals; they, or their precursors, must be ingested from dietary sources and transported to the brain. During late gestation and the early postnatal period, neurodevelopment is exceptionally rapid, and substantial amounts of PUFAs, especially DHA, are critical to ensure neurite outgrowth as well as proper brain and retina development. Here, we review the various functions of DHA in the nervous system, the proteins involved in its internalization and metabolism into phospholipids, and its relationship to several neurological disorders, including Alzheimer's disease and depression.
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PMID:Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. 1621 10

The objective of this study was to investigate the effect of individual PUFAs on LDL receptor (LDLr) expression in human fibroblasts and HepG2 cells, and to evaluate whether acyl CoA:cholesterol acyltransferase (ACAT) and sterol regulatory element-binding protein 1 (SREBP-1) were involved in the regulation of LDLr expression by fatty acids. When fibroblasts and HepG2 cells were cultured with serum-free defined medium for 48 h, there was a 3- to 5-fold (P < 0.05) increase in LDLr protein and mRNA levels. Incubation of fibroblasts and HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH-cholesterol, 5 mg/L) for 24 h decreased LDLr protein and mRNA levels by 50-90% (P < 0.05). Arachidonic acid [AA, 20:4(n-6)], EPA [20:5(n-3)], and DHA [22:6(n-3)] antagonized the depression of LDLr gene expression by 25OH-cholesterol and increased LDLr protein abundance 1- to 3-fold (P < 0.05), but had no significant effects on LDLr mRNA levels. Oleic (18:1), linoleic (18:2), and alpha-linolenic acids [18:3(n-3)] did not significantly affect LDLr expression. ACAT inhibitor (58-035, 1 mg/L) attenuated the regulatory effect of AA on LDLr protein abundance by approximately 40% (P < 0.05), but did not modify the regulatory effects of other unsaturated fatty acids in HepG2 cells. The present results suggest that AA, EPA, and DHA increase LDLr protein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels. Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein.
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PMID:Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells. 1625 8

We investigated the influence of PUFA in phospholipids (PL) on the functional characteristics of cultured cardiomyocytes (CM) in basal conditions and during free radical (FR) stress provoked either by the xanthine/xanthine oxidase (X/XO) system or by a (9Z, 11E, 13 (S), 15Z)-13-hydroperoxyoctadecatrienoic acid (13-HpOTrE). CM were grown in media containing either n - 3 (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA) or n - 6 (arachidonic acid, AA). These two groups of CM displayed different PUFA n - 6/n - 3 ratio in PL. However, their basal electromechanical characteristics were similar. The X/XO system drastically altered CM functions, without difference between the two groups of CM. 13-HpOTrE caused a moderate and reversible depression in action potential parameters, which was dependent upon the PL PUFA, since the n - 3-enriched CM exhibited an earlier functional depression but faster recovery. Thus, the peroxidative damage of CM depended on a cross relationship between FR species and the PL PUFA composition.
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PMID:Dependence on the phospholipid polyunsaturated fatty acids of the oxidative injury of isolated cardiomyocytes. 1648 41

Among polyunsaturated omega-3 fatty acids, ALA (alpha-linolenic acid) provided the first coherent multidisciplinary experimental demonstration of the effect of diet (one of its major macronutrient) on the structure, the biochemistry, the physiology and thus the function of the brain. In fact, DHA (docosahexaenoic acid) is one for the major building structures of membrane phospholipids of brain and absolute necessary of neuronal function. It was first demonstrated that the differentiation and functioning of cultured brain cells requires not only ALA, but also the very long polyunsaturated omega-3 (DHA) and omega-6 carbon chains. Then, it was found that ALA acid deficiency alters the course of brain development, perturbs the composition of brain cell membranes, neurones, oligodendrocytes and astrocytes, as well as sub cellular particles such as myelin, nerve endings (synaptosomes) and mitochondria. These alterations induce physicochemical modifications in membranes, lead to biochemical and physiological perturbations, and results in neurosensory and behavioural upset. Consequently, the nature of polyunsaturated fatty acids (in particular omega-3, ALA and DHA) present in formula milks for infants (premature and term) conditions the visual, neurological and cerebral abilities, including intellectual. Dietary omega-3 fatty acids are involved in the prevention of some aspects of ischemic cardiovascular disease (including at the level of cerebral vascularization), and in some neuropsychiatric disorders, particularly depression, as well as in dementia, including Alzheimer's disease and vascular dementia. The implication of omega-3 fatty acids in major depression and bipolar disorder (manic-depressive illness) is under evaluation. Their dietary deficiency (and altered hepatic metabolism) can prevent the renewal of membranes and consequently accelerate cerebral ageing; nonetheless, the respective roles of the vascular component on one hand and the cerebral parenchyma itself on the other have not yet been clearly elucidated. Low fat diet may have adverse effects on mood. The nature of the amino acid composition of dietary proteins contributes to cerebral function; taking into account that tryptophan plays a special role. In fact, some indispensable amino acids present in dietary proteins participate to elaborate neurotransmitters (and neuromodulators). The regulation of glycaemia (thanks to the ingestion of food with a low glycaemic index ensuring a low insulin level) improves the quality and duration of intellectual performance, if only because at rest the brain consumes more than 50% of dietary carbohydrates, approximately 80% of which are used only for energy purpose. In infants, adults and aged, as well as in diabetes, poorer glycaemic control is associated with lower performances, for instance on tests of memory. At all ages, and more specifically in aged people, some cognitive functions appear sensitive to short term variations in glucose availability. The presence of dietary fibbers is associated with higher alertness ratings and ensures less perceived stress. Although an increasing number of genetic factors that may affect the risk of neurodegenerative disorders are being identified, number of findings show that dietary factors play major roles in determining whether the brain age successfully of experiences neurodegenerative disorders. Effects of micronutrients have been examined in the accompanying paper.
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PMID:Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 2 : macronutrients. 1706 10


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