Reduced long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been reported in adult patients suffering from depression and bipolar disorder (BD). LCn-3PUFA status has not previously been examined in children and adolescents with BD compared with healthy controls. Fifteen children and adolescents (9-18 years, M +/- SD = 14.4 +/- 3.48) diagnosed with juvenile bipolar disorder (JBD) and fifteen healthy age and sex-matched controls were assessed for dietary intake and fasting red blood cell (RBC) membrane concentrations of LCn-3PUFA. Fatty acid concentrations were compared between participants diagnosed with JBD and controls after controlling for dietary intake. RBC membrane concentrations of EPA and DHA were not significantly lower in participants diagnosed with JBD compared with healthy controls (M +/- sem EPA = 3.37 +/- 0.26 vs. 3.69 +/- 0.27 microg/mL, P = 0.458; M +/- sem DHA = 22.08 +/- 2.23 vs. 24.61 +/- 2.38 microg/mL, P = 0.528) after controlling for intake. Red blood cell DHA was negatively (r =-0.55; P = 0.044) related to clinician ratings of depression. Although lower RBC concentrations of LCn-3PUFA were explained by lower intakes in the current study, previous evidence has linked reduced LCn-3PUFA to the aetiology of BD. As RBC DHA was also negatively related to symptoms of depression, a randomised placebo-controlled study examining supplementation with LCn-3PUFA as an adjunct to standard pharmacotherapy appears warranted in this patient population.

PURPOSE OF REVIEW: There is increasing evidence from epidemiological, case-control and randomized clinical trials for a link between omega-3 deficiency and the development of mood disorders. This article examines recent evidence for this association. RECENT FINDINGS: During the past year our understanding of the effect of omega-3 depletion on the structure and function of the brain has been furthered by research examining human brain tissue and by studies utilizing animal models of depression. Human and animal research has also provided further evidence for omega-3 affecting mood via its anti-inflammatory effects. Previous clinical trials indicated that omega-3 can be effective as an adjunctive treatment for those with treatment-resistant depression. More recent clinical trial data indicate that omega-3 may also be an effective monotherapy for childhood depression and for depressed mood in patients who engage in recurrent self-harm. The recent clinical trial data regarding omega-3 as a treatment for bipolar disorder are inconclusive, however, and clinical trials in postnatal depression are still lacking. SUMMARY: This article reviews the most important recent papers in this burgeoning and interesting research area.

The identification, referral and specific treatment of midlife patients in primary care who are distressed by mood, anxiety, sleep and stress-related symptoms, with or without clinically confirmed menopausal symptoms, are confounded by many structural issues in the delivery of women's healthcare. Diagnosis, care delivery, affordability of treatment, time commitment for treatment, treatment specificity for a particular patient's symptoms and patient receptiveness to diagnosis and treatment all play roles in the successful amelioration of symptoms in this patient population. The value of screening for depression in primary care, the limitations of commonly used screening instruments relative to culture and ethnicity, and which clinical care systems make best use of diagnostic screening programs will be discussed in the context of the midlife woman. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) program illustrates the relatively high rate of unremitted patients, regardless of clinical setting, who are receiving antidepressants. Nonmedication treatment approaches, referred to in the literature as 'nonsomatic treatments', for depression, anxiety and stress, include different forms of cognitive-behavioral therapy, interpersonal therapy, structured daily activities, mindfulness therapies, relaxation treatment protocols and exercise. The specificity of these treatments, their mechanisms of action, the motivation and time commitment required of patients, and the availability of trained practitioners to deliver them are reviewed. Midlife women with menopausal symptoms and depression/anxiety comorbidity represent a challenging patient population for whom an individualized treatment plan is often necessary. Treatment for depression comorbid with distressing menopausal symptoms would be facilitated by the implementation of a collaborative care program for depression in the primary care setting.

Polyamines are a class of aliphatic compounds which include putrescine, cadaverine, spermine and spermidine. They are involved in a variety of cellular processes and have been implicated in a number of different pathophysiological mechanisms. Polyamines are volatile compounds having a distinctive odour normally perceived as being unpleasant. The measurement of their abundance has, however, been restricted to compounds present in the aqueous phase. Using selected ion flow tube mass spectrometry (SIFT-MS) we have shown that the polyamines react with the ions H(3)O(+), NO(+) and O(2)(+) to form distinctive product ions allowing their levels to be quantified in the vapour phase. The low volatility of spermine did not allow extensive analysis of this compound by SIFT-MS while the adherent properties of cadaverine and putrescine required the use of PTFE transfer lines and couplers. Our data suggested the presence of cadaverine and putrescine in both oral air and the headspace of putrefying bovine muscle, while product ions corresponding to putrescine and spermidine were found in the headspace of human semen. SIFT-MS therefore appears to be a practical means of measuring vapour-phase polyamine levels, having applications in biology, medicine and dentistry, and food science. Copyright (c) 2009 John Wiley & Sons, Ltd.

Anxiety disorders are a common group of psychiatric illnesses which have significant personal, family and societal costs. Current treatments have limited efficacy in many patients highlighting a need for new therapeutic approaches to be explored. Anxiety disorders exhibit marked comorbity with mood disorders suggesting the existence of mechanistic similarities. Such a notion is supported by observations that some conventional pharmacotherapies are both effective antidepressants and anxiolytics. As such, given that omega-3 PUFA supplementation may be effective in the treatment of major depressive disorder it is reasonable to propose that they may also possess anxiolytic properties. Experimental data in support of such a hypothesis is currently lacking although reduced abundance of omega-3 PUFA have been reported in patients with anxiety, while supplementation with omega-3 PUFA appears to inhibit activation of the HPA axis and can ameliorate some of the symptoms of anxiety. Clinical investigations carried out to date have, however, involved small numbers of participants. Larger trials using a variety of omega-3 PUFA species in clinically well-defined patients with anxiety will be required to demonstrate a therapeutic role for omega-3 PUFA in these disorders. Given the excellent side effect profile of omega-3 PUFA as well as their strong theoretical rationale, such future trials appear justified.

BACKGROUND: Cigarette smoking is believed to cause oxidative stress by several mechanisms, including direct damage by radical species and the inflammatory response induced by smoking, and would therefore be expected to cause increased lipid peroxidation. The aim was to carry out the first study of the relationship of smoking in humans to the level of n-3 lipid peroxidation indexed by the level of ethane in exhaled breath. METHODS: Samples of alveolar air were obtained from 11 smokers and 18 non-smokers. The air samples were analyzed for ethane using mass spectrometry. RESULTS: The two groups of subjects were matched with respect to age and gender. The mean cumulative smoking status of the smokers was 11.8 (standard error 2.5) pack-years. The mean level of ethane in the alveolar breath of the group of smokers (2.53 (0.55) ppb) was not significantly different from that of the group of non-smokers (2.59 (0.29) ppb; p = 0.92). With all 29 subjects included, the Spearman rank correlation coefficient between ethane levels and cumulative smoking status was -0.11 (p = 0.58), while an analysis including only the smokers yielded a corresponding correlation coefficient of 0.11 (p = 0.75). CONCLUSION: Our results show no evidence that cigarette smoking is related to increased n-3 lipid peroxidation as measured by expired ethane.

BACKGROUND: This study tested the hypothesis that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of n-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder. METHODS: Samples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 x 70 x 70 mm3 voxel). The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra. RESULTS: The ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (rs = 0.714, p < 0.05). CONCLUSION: Our results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral n-3 lipid peroxidation. From a practical viewpoint, if human cerebral n-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.

This study directly assessed whether there was a change in the level of exhaled ethane, which provides a non-invasive, quantitative, direct measure of n-3 lipid peroxidation, in the breath of patients with schizophrenia. Samples of alveolar air were obtained from 20 subjects with schizophrenia and 23 age- and sex-matched healthy control subjects. The air samples were analyzed for ethane using mass spectrometry. The mean level of ethane in the schizophrenia sample [5.15 (S.E. 0.56) ppb] was significantly higher than that of the healthy controls [2.63 (S.E. 0.31) ppb; p<0.0005]. A further sub-analysis showed that nicotine dependence was unlikely to be the cause of this difference. These results suggest that the measurement of exhaled ethane levels may offer a non-invasive direct biomarker of increased n-3 lipid peroxidation in schizophrenia.

Thermal desorption (TD) is commonly employed for volatile chemical analysis, it being the method of choice for occupational health and safety monitoring. TD allows for offline capture of volatiles onto a solid sorbent followed by desorption and analysis at a later time. Although TD is routinely used in conjunction with gas chromatography (TD-GC), the assay throughput is low and requires the use of gas standards for quantification. Another technique increasingly employed for volatile chemical analysis, selected ion flow tube mass spectrometry (SIFT-MS), is capable of real-time absolute (i.e. without calibration standards) quantification of volatile chemicals present at single digit parts per billion or higher concentrations. SIFT-MS is, however, normally used for online direct analysis of gas samples rather than offline collection and analysis. The goal of this study was to determine whether a combination of TD and SIFT-MS could be used to quantify volatile compounds, specifically xylene and toluene, more rapidly than TD-GC and without the need for calibration standards. SIFT-MS was able to quantify xylene and toluene levels within 45 s of desorption. Due to the robustness of the SIFT-MS analysis in the presence of water vapour and other major components of air, the purging of tubes usually required to remove these constituents during the TD cycle was not required, therefore reducing the TD cycle time. Comparing the quantity of xylene and toluene applied to the TD tube with the absolute levels quantified by SIFT-MS subsequent to desorption suggested a recovery of over 95% of the applied compound. We conclude that the combination of TD and SIFT-MS allows more rapid and accurate quantification of xylene and toluene (compared with TD-GC) to be achieved without the need for calibration standards, features which may be advantageous in applications requiring rapid analysis and high throughput. Copyright (c) 2007 John Wiley & Sons, Ltd.

Omega-3 polyunsaturated fatty acids (PUFA) are increasingly finding use as treatments for a variety of medical conditions. PUFA supplementation can, however, result in increased oxidative stress causing elevated turnover rate of membrane phospholipids, impairment of membrane integrity and increased formation of inflammatory mediators. The aim of this study was to determine which antioxidant compounds were most effective in ameliorating the stimulation of phospholipid turnover by oxidative stress. U937 cells were supplemented with eicosapentaenoic acid and either ascorbic acid, alpha-tocopherol, beta-carotene or astaxanthin prior to being challenged with oxidant. Although all antioxidants were found to be effective in decreasing oxidant-stimulated peroxide formation, only alpha-tocopherol significantly decreased oxidant-stimulated release of (3)H-labeled arachidonic acid (AA), while ascorbic acid markedly increased release. All antioxidants except alpha-tocopherol decreased oxidant-stimulated (3)H-AA uptake. Our data suggest that antioxidants are not equally effective in combating the effects of oxidative stress upon membrane phospholipid turnover, and that optimal protection will require mixtures of antioxidants.

Phospholipases A(2)(PLA(2)) are a family of enzymes involved in membrane phospholipid metabolism and cell signalling. The gene encoding one form, type VI calcium-independent phospholipase A(2), is located in a region of DNA that may contain a gene important in the aetiology of psychosis. Moreover, the activity of calcium-independent PLA(2) is reported to be elevated in the blood and brain of patients with schizophrenia. In this study we determined whether a similar change takes place in patients with bipolar disorder with and without a history of psychosis. Methods: Serum calcium-independent and -dependent PLA(2) activities were determined in 24 patients with bipolar I disorder. Results: Serum calcium-independent and -dependent PLA(2) activities in bipolar cases did not differ significantly from that in healthy volunteers (HVs). However, calcium-independent PLA(2) activity was significantly (p < 0.05) higher in patients with a history of psychosis compared with those with no history of psychosis (by 55%) or to HVs (by 31%). Conclusions: Our data suggest that a subset of bipolar I disorder patients with a history of psychosis have elevated calcium-independent PLA(2) activity. Given that this enzyme activity is also increased in schizophrenia, elevated rates of phospholipid turnover mediated by the enzyme could represent a common biochemical feature of psychotic illness.

The use of n-3 polyunsaturated fatty acids, as found in fish-oil derived dietary supplements, as anti-inflammatory agents is supported by a variety of biochemical and physiological data. Recent studies investigating the therapeutic potential of long chain (>C20) n-3 fatty acids in mental illness have lead to the conclusion, however, that not all n-3 fatty acid types are equally efficacious. In particular eicosapentaeoic acid (EPA) appears to possess antidepressant and antipsychotic activity, while docosahexaenoic acid (DHA) does not, an effect suggested to be due to a differential ability to antagonize arachidonic acid (AA)-dependent cell signalling. In this study, we examine the effect of EPA and DHA supplementation upon uptake and release of arachidonic acid stimulated by tert-butyl hydroperoxide/Fe2+ in U937 cells. Oxidant-stimulated 3H-AA release from cells was enhanced by pre-treatment with EPA, DHA and AA, but not stearic or oleic acids for 18 days, with the order of effect magnitude being EPA > DHA = AA. Supplementation of cells for 1 day gave qualitatively similar results, although the effect magnitude was smaller. To determine whether enhanced release was due to decreased reuptake of AA, cells were cultured in the presence of 10 microM fatty acids. Pre-treatment of cells with EPA, and to a lesser extent AA, but not DHA, inhibited uptake of 3H-AA measured subsequent to the removal of unesterified fatty acids. This study suggests that, in U937 cells, EPA can alter the rate of uptake and release of AA from phospholipids in an exposure time-dependent manner, whereas DHA has no or little effect. Our results predict that EPA will have a more pronounced effect upon AA-dependent processes compared to DHA, and suggests that the relative amounts of EPA and DHA in fish oil supplements may modify their biochemical, and potentially, behavioural effects.

BACKGROUND: Recent evidence has suggested an important role for lipids in the etiology and treatment of depression. Methylnicotinate-induced vasodilation can be used to investigate lipid-dependent signalling mechanisms involving the phospholipase A2 (PLA2)/cyclooxygenase pathway, an important signalling system involved in the action of several neurotransmitters including serotonin. To investigate whether abnormalities in this signalling system may occur in depressive illness, we undertook a study of methylnicotinate response in unipolar depression (UD). METHODS: Methylnicotinate was applied to the forearm of 20 patients with depression and 38 age and sex-matched healthy volunteers (HV). The resulting erythema was assessed over a 15-min period. RESULTS: Methylnicotinate-induced erythema was reduced in subjects with depression compared to HV at 5 min after application, it returned to normal after 15 min. Thus, although the maximal response to methylnicotinate appears normal, patients with UD exhibit an apparently delayed response. LIMITATIONS: The major limitation is that all unipolar patients were medicated at the time of testing. CONCLUSIONS: Our results support the hypothesis that UD may be associated with abnormalities in lipid-associated signalling systems, and may provide insight into how lipid intake may modulate depressive symptoms.

Omega-3 polyunsaturated fatty acid (omega-3 PuFA) therapy shows promise in primary and secondary prevention of cardiovascular diseases.

Anxiety disorders are a common group of psychiatric illnesses which have significant personal, family and societal costs. Current treatments have limited efficacy in many patients highlighting a need for new therapeutic approaches to be explored. Anxiety disorders exhibit marked comorbity with mood disorders suggesting the existence of mechanistic similarities. Such a notion is supported by observations that some conventional pharmacotherapies are both effective antidepressants and anxiolytics. As such, given that omega-3 PUFA supplementation may be effective in the treatment of major depressive disorder it is reasonable to propose that they may also possess anxiolytic properties. Experimental data in support of such a hypothesis is currently lacking although reduced abundance of omega-3 PUFA have been reported in patients with anxiety, while supplementation with omega-3 PUFA appears to inhibit activation of the HPA axis and can ameliorate some of the symptoms of anxiety. Clinical investigations carried out to date have, however, involved small numbers of participants. Larger trials using a variety of omega-3 PUFA species in clinically well-defined patients with anxiety will be required to demonstrate a therapeutic role for omega-3 PUFA in these disorders. Given the excellent side effect profile of omega-3 PUFA as well as their strong theoretical rationale, such future trials appear justified.

Interest in the role of polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) omega-3 (n-3) PUFAs, in mental health is increasing. This review investigates whether n-3 PUFA levels are abnormal in people with three prevalent mental health problems - attention deficit hyperactivity disorder, depression, and dementia. Data sources included PubMed, Web of Science, and bibliographies of papers published in English that describe PUFA levels in the circulation of individuals who have these mental health conditions. Although abnormal blood PUFA levels were reported in a number of studies, weighted comparisons of PUFA status showed no significant differences overall between people with mental health problems and controls. Whether those with low n-3 PUFA status are likely to be more responsive to n-3 PUFA supplementation is not yet resolved. Further studies assessing PUFA levels and mental status with greater uniformity are required in order to clarify the relationship between LC n-3 PUFA status and mental health.

The delta-5 and delta-6 desaturases are key enzymes in the metabolism of omega-3 (omega-3) and omega-6 (omega-6) polyunsaturated fatty acids (PUFA), which in turn influence cellular functions by regulating several metabolic pathways with well-known effects on the cardiovascular system. At present, data about desaturase activity and cardiovascular risk remain inconclusive. In this short review we propose a 'desaturase hypothesis' of atherosclerosis, providing suggestions for the Janus-faced role of desaturases, with both more favorable (mainly related to omega-3 long-chain fatty acids) and more harmful (mainly related to omega-6 long-chain fatty acids) cardiovascular effects than those obtained in subjects with lower desaturase activity. In particular in populations eating a Western diet rich in omega-6 PUFA, a high desaturase activity may promote an increased bioavailability of arachidonic acid with prevailing synthesis of arachidonic acid-derived proinflammatory eicosanoids, finally favoring atherosclerotic vascular damage. In contrast, high desaturase activity in subjects consuming a diet rich in omega-3 PUFA or receiving omega-3 PUFA supplementation could result in the opposite situation with a preferential synthesis of anti-inflammatory eicosanoids. For these reasons, carriers of specific FADS haplotypes may be predisposed to more pronounced vascular inflammatory damage, but also to an increased beneficial effect with omega-3 PUFA supplementation.

Incorporation of dietary n-3 polyunsaturated fatty acids (PUFA) into bone may optimize bone development. The study objective was to use the fat-1 mouse, a transgenic model that synthesizes n-3 PUFA from n-6 PUFA, to determine if bone mineral density (BMD) and biomechanical bone strength were favourably modulated by lowering the n-6/n-3 PUFA ratio in vertebrae. Male and female wild-type and fat-1 mice were fed an AIN93-G diet containing 10% safflower oil from weaning through 12 weeks of age. Vertebrae BMD was determined by dual energy x-ray absorptiometry and peak load, a surrogate measure of fracture risk, was measured by a materials testing system. Vertebrae fatty acid composition was measured by gas liquid chromatography. At 12 weeks of age, vertebrae peak load was higher in fat-1 mice compared to wild-type (P = 0.026). Fat-1 mice also had lower n-6/n-3 PUFA ratio in vertebrae than wild-type (P < 0.001) and this ratio was negatively correlated with BMD and peak load (P = 0.005). Moreover, n-3 PUFA including alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid were positively correlated (P < 0.05) with BMD and peak load. Therefore, a lower vertebrae n-6/n-3 PUFA ratio is associated with stronger vertebrae and suggests a positive role for n-3 PUFA in bone development.

Dogs demonstrate an age-related cognitive decline, which may be related to a decrease in the concentration of omega-3 polyunsaturated fatty acids (n-3 PUFA) in the brain. Medium chain triglycerides (MCT) increase fatty acid oxidation, and it has been suggested that this may raise brain n-3 PUFA levels by increasing mobilization of n-3 PUFA from adipose tissue to the brain. The goal of the present study was to determine whether dietary MCT would raise n-3 PUFA concentrations in the brains of aged dogs. Eight Beagle dogs were randomized to a control diet (n = 4) or an MCT (AC-1203) enriched diet (n = 4) for 2 months. The animals were then euthanized and the parietal cortex was removed for phospholipid, cholesterol and fatty acid determinations by gas-chromatography. Dietary enrichment with MCT (AC-1203) resulted in a significant increase in brain phospholipid and total lipid concentrations (P < 0.05). In particular, n-3 PUFA within the phospholipid, unesterified fatty acid, and total lipid fractions were elevated in AC-1203 treated subjects as compared to controls (P < 0.05). Brain cholesterol concentrations did not differ significantly between the groups (P > 0.05). These results indicate that dietary enrichment with MCT, raises n-3 PUFA concentrations in the parietal cortex of aged dogs.

Omega-3 and omega-6 poly-unsaturated fatty acids (PUFA) are the major families of PUFA that can be found as components of the human diet. After ingestion, both omega-3 and omega-6 PUFA are distributed to every cell in the body where they are involved in a myriad of physiological processes, including regulation of cardiovascular, immune, hormonal, metabolic, neuronal, and visual functions. At the cellular level, these effects are mediated by changes in membrane phospholipids structure, by interference with eicosanoid intracellular signaling, and by regulation of gene expression. The literature suggests the antiepileptic properties of PUFA, although these evidences emerge from basic science rather than from clinical trials. Several hypotheses have been suggested to explain the anticonvulsive effects of PUFA: modification of the membrane fluidity, direct action of PUFA on cell membrane ionic channels and/or receptors, modulation of inflammatory responses. Regarding the published clinical trials, the data are conflicting. It is currently not known whether different doses or different omega-3: omega-6 ratios would be effective.

OBJECTIVES: Both omega-3 and omega-6 long-chain polyunsaturated fatty acids (PUFA) have a substantial impact on human brain development and function. However, in western industrial countries omega-3 LC-PUFA in particular are often lacking in diets. Increasing evidence indicates that LC-PUFA imbalance or deficiencies may be associated with Attention Deficit/Hyperactivity Disorder (ADHD) through involvement in the dopaminergic corico-striatal metabolism. Preliminary study result suggest that dietary supplementation with LC-PUFA might be effective in the treatment of ADHD. METHODS: This review summarizes the knowledge in terms of a hypothesized pathogenetic relationship between fatty acid metabolism and ADHD and discusses the possible clinical benefit of a primary or combined treatment with LC-PUFA. RESULTS: Actually it is unclear whether a deficit in intake or metabolism of LC-PUFA may play a major role in the pathogenesis of ADHD. Moreover treatment studies yielded conflicting results. A combination of Omega-3 and Omega-6 - fatty acids might attenuate the symptoms of ADHD significantly, thus making this dietary intake useful. CONCLUSIONS: Considerable research has to be done in the future to identify ideal therapeutic combinations and dosages of various fatty acids, and to develop reliable ways of defining those individuals to benefit from this treatment access.

ABSTRACT: BACKGROUND: A growing number of observational and epidemiological studies have suggested that mental illness, in particular mood disorders, is associated with reduced dietary intake and/or cellular abundance of omega-3 polyunsaturated fatty acids (PUFA). This has prompted researchers to test the efficacy of omega-3 PUFA in a range of different psychiatric disorders. We have critically reviewed the double blind placebo controlled clinical trials published prior to April 2007 to determine whether omega-3 PUFA are likely to be efficacious in these disorders. Most trials involved a small number of participants but were largely well designed. RESULTS: Omega-3 PUFA were well tolerated by both children and adults with mild gastrointestinal effects being the only consistently reported adverse effect. For schizophrenia and borderline personality disorder we found little evidence of a robust clinically relevant effect. In the case of attention deficit hyperactivity disorder and related disorders, most trials showed at most small benefits over placebo. A limited meta-analysis of these trials suggested that benefits of omega-3 PUFA supplementation may be greater in a classroom setting than at home. Some evidence indicates that omega-3 PUFA may reduce symptoms of anxiety although the data is preliminary and inconclusive. The most convincing evidence for beneficial effects of omega-3 PUFA is to be found in mood disorders. A meta-analysis of trials involving patients with major depressive disorder and bipolar disorder provided evidence that omega-3 PUFA supplementation reduces symptoms of depression. Furthermore, meta-regression analysis suggests that supplementation with eicosapentaenoic acid may be more beneficial in mood disorders than with docosahexaenoic acid, although several confounding factors prevented a definitive conclusion being made regarding which species of omega-3 PUFA is most beneficial. The mechanisms underlying the apparent efficacy of omega-3 PUFA in mood disorders compared to schizophrenia are discussed as is a rational for the possibly greater efficacy of EPA compared to DHA. CONCLUSIONS: While it is not currently possible to recommend omega-3 PUFA as either mono- or adjunctive-therapy in any mental illness, the available evidence is strong enough to justify continued study, especially with regard to attentional, anxiety and mood disorders.

According to a recent publication in Nature Medicine an increased dietary intake of omega-3-polyunsaturated fatty acids (PUFA) may protect against the development and progression of retinal neovascularization. The study conducted by L. Smith et al. of the Children's Hospital Boston attracts world-wide attention. In a mouse model of oxygen-induced retinopathy the researchers were able to demonstrate that neonatal mice kept on a "Japanese diet"(i.e. rich in omega-3-PUFA) developed about 50% less retinal neovascularization as compared to mice kept on a "Western diet"(rich in omega-6-PUFA). The results are now being followed-up by a clinical study with the aim to investigate whether prematurely born infants with a high risk of developing ROP may benefit from a diet supplemented with omega-3-PUFA. In addition, the AREDS2-Study which commenced in October 2006 is examining the role of omega-3-PUFA in the development and progression of age-related macular degeneration.