Omega-3 polyunsaturated fatty acids supplementation improves memory in first-diagnosed, drug-naïve patients with depression: Secondary analysis of data from a randomized controlled trial.

INTRODUCTION: Cognitive impairments are found in most patients with major depressive disorder (MDD). It is believed that low Omega-3 polyunsaturated fatty acids (n-3 PUFAs) level raise the risk of anxiety, depressive symptoms and cognition dysfunction. Since our previous research has found n-3 PUFAs supplementation improves anxiety in MDD, this study was to further explore the effectiveness on cognitive impairment among depressed patients. METHODS: A total of 72 venlafaxine treated outpatients with first-diagnosed, drug-naïve depression were enrolled. Daily n-3 PUFAs supplementation (2.4 g/d of fish oil, including 1440 mg eicosapentaenoic acid and 960 mg of docosahexaenoic acid) or placebo was used for 12 weeks. Cognitive function, measure by repeatable battery for the assessment of neuropsychological status ([RBANS]) scores, was compared over time. RESULTS: Immediate memory, delayed memory and RBANS total scores were significant higher in both groups at week 4 and week 12 compared with baseline. Both groups exhibited improvement on attention scores at week 12. No significant differences were observed comparing n-3 PUFAs with placebo groups in the improvement of total RBANS scores and other subscales except in the change of immediate memory at both week 4 and week 12 (p < 0.05). LIMITATIONS: Sample size was relatively low. Moreover, multiple ethnic populations and the income of patients should be considered. Lastly, we used raw scores instead of the standardized scores of RBANS. CONCLUSION: N-3 PUFAs supplementation yielded a small but statistically significant improvement on immediate memory in first-diagnosed, drug-naïve depressed patients. While, antidepressant treatment resulted in significant improvement of cognitive function.

Potential antidepressant-like effects of N-3 polyunsaturated fatty acids through inhibition of endoplasmic reticulum stress.

RATIONALE: The growing evidence has demonstrated the importance of endoplasmic reticulum stress (ERS) in the pathophysiology of depression. ERS genes were considered to be potential novel therapeutic targets for depression. OBJECTIVES: To clarify the mechanisms of the chronic unpredictable mild stress (CUMS)-induced ERS response and the potential contributing pathways in depression, and further investigate the potential link between N-3 polyunsaturated fatty acids (PUFAs) and stress-induced ERS disturbances. METHODS: This study analyzed the expression of ERS-related genes including GRP78, ATF-4, ATF-6, XBP-1, and CHOP, and sigma-1R with real-time PCR in peripheral blood mononuclear cell (PBMC) RNA samples from participants. All of the rats except for those in the control groups were subjected to 5 consecutive weeks of CUMS to establish the depression model, and the antidepressant effects of N-3 PUFAs were observed by behavior tests. Moreover, the effect of diet and stress on the ERS pathways was also investigated using the western blot. RESULTS: Blood CHOP, ATF-4, and XBP-1 levels were notably elevated in depressed patients relative to healthy individuals. Moreover, increased sigma-1R and decreased ATF-6 implied the protective role of sigma-1R through modulating ERS in patients with depression. Animal studies disclosed the novel findings that supplementary N-3 PUFAs in rats alleviated CUMS-induced disturbance of ERS through the ATF-4/XBP-1/CHOP pathway, implying its potential strategy for depression. CONCLUSION: CUMS-induced depressive-like behaviors are related to the disturbance of ERS. Furthermore, supplementary N-3 PUFAs might be an effective way to alleviate ERS.

Nutrition and schizophrenia: associations worthy of continued revaluation.

BACKGROUND: Accumulating evidence have shown that diet and nutrition play significant roles in mental illness, such as depression, anxiety and bipolar disorder. However, comprehensive evaluation of the relationship between nutrition and schizophrenia is lacking. OBJECTIVE: The present review aims to synthetic elaborate the associations between nutrition and schizophrenia. Relevant studies on dietary patterns, macronutrients, micronutrients were performed through a literature search to synthesize the extracted data. SUMMARY: Dietary interventions may help prevent the occurrence of schizophrenia, or delay symptoms: Healthy diets like nutritious plant-based foods and high-quality protein, have been linked to reducing the risk or symptoms of schizophrenia. Moreover, diet high in saturated fat and sugar is linked to more serious outcomes of schizophrenia. Additionally, when N-acetylcysteine acts as an adjuvant therapy, the overall symptoms of schizophrenia are significantly reduced. Also nascent evidence showed mental disorders may be related to intestinal microbiota dysfunction. Our study offered important insights into the dietary habits of patients with schizophrenia and the potential impact of nutritional factors on the disease. We also emphasized the need for further research, particularly in the form of large randomized double-blind controlled trials, to better understand the effects of nutrients on schizophrenia symptoms in different populations and disease types.

Grass pollen exposure is associated with higher readmission rates for pediatric asthma.

BACKGROUND: Pediatric asthma hospital readmission is a burden on the individual and costly for Australian hospitals. Grass pollen's role, a known trigger for asthma admissions, is unexamined in readmissions. We examined the association between grass pollen and pediatric asthma readmission. METHODS: The Victorian Admitted Episodes Dataset was used to identify all primary admissions with a principal diagnosis of asthma in children aged 2-18 years between 1997 and 2009. Readmissions were defined as subsequent admissions within 28 days of index admission discharge. Generalized additive models were used to assess associations between readmission, grass pollen season, and daily grass pollen counts, lagged and cumulative. Models were further stratified by sex and age group. RESULTS: Mean daily readmission was higher during grass pollen season than other times of the year, incidence rate ratio (IRR) 1.44 (95% CI, 1.03, 2.02) and for children aged 2-5 years, IRR 1.99 (1.26, 3.14). Same day grass pollen was nonlinearly associated with daily readmission for the 13-18 age group between 110 and 256 grains/m3 , p < .01. Lag 2 grass pollen was nonlinearly associated with daily readmissions overall (p = .03), boys (p = .01), and younger age groups 2-5 (p = .02) and 6-12 (p < .001). CONCLUSIONS: Grass pollen exposure was associated with higher readmission rates for pediatric asthma. Treatment plans prior to discharge could be implemented to reduce the likelihood of readmission by younger children during the pollen season.

The role of short-term grass pollen exposure in food skin-prick test reactivity, food allergy, and eczema flares in children.

BACKGROUND: While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children. METHODS: We investigated 1- (n = 1108) and 6-year-old (n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. RESULTS: Grass pollen at lag 0-3 (every 20 grains/m3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only. CONCLUSION: Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold.

A pragmatic approach to infant feeding for food allergy prevention.

Early introduction of allergenic foods into an infant's diet is currently the most promising strategy to prevent food allergy, with infant guidelines around the world shifting from promoting avoidance to actively encourage the introduction of allergenic foods in the infant diet. Infant feeding guidelines vary according to regional public health priorities, and knowledge gaps remain, resulting in ongoing challenges for clinicians and families to translate guidelines into practical strategies for the introduction of complementary foods for food allergy prevention. Evidence from Australia demonstrates high community support and uptake of revised guidelines with most parents introducing allergenic foods in the first year of life, although this has not had the expected impact on substantially reducing food allergy prevalence. To uptake of guidelines from other countries is less clear, and several barriers have been noted in infant feeding RCTs, which may warrant intervention strategies. Further research is needed to understand additional strategies for food allergy prevention, particularly in infants who develop food allergy prior to when they are developmentally ready to commence solids. Several RCTs are underway investigating preventative strategies that target the window before allergen ingestion, such as vitamin D supplementation, emollient use, and immunizations that prime the immune response away from a Th2-driven allergic phenotype. Further research is also needed to understand the role of the environment and the host environment in the development of tolerance to foods.

Omega-3 Polyunsaturated Fatty Acids Supplementation Alleviate Anxiety Rather Than Depressive Symptoms Among First-Diagnosed, Drug-Naïve Major Depressive Disorder Patients: A Randomized Clinical Trial.

Background: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) augmentation of antidepressants has shown great potential in the prevention and treatment of major depressive disorders (MDD). Objective: To investigate the effect of n-3 PUFAs plus venlafaxine in patients with first-diagnosed, drug-naïve depression. Method: A total of 72 outpatients with first-diagnosed depression were recruited. The daily dose of 2.4 g/day n-3 PUFAs or placebo plus venlafaxine was used for over 12 weeks. The outcomes were assessed by the Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), Beck depression inventory (BDI), and Self-rating anxiety scale (SAS). Results: Both groups exhibited improvement on clinical characteristics at week 4 and week 12 compared with baseline. The rate of responders for anxiety in n-3 PUFAs group (44.44%) was significantly higher than that in placebo group (21.21%) at week 4 (χ2 = 4.182, p = 0.041), while week 12 did not show a difference (χ2 = 0.900, p = 0.343). The rate of responders for depression at both week 4 (χ2 = 0.261, p = 0.609) and week 12 (χ2 = 1.443, p = 0.230) showed no significant difference between two groups. Further analysis found that Childhood Trauma Questionnaire (CTQ) had positive correlation with HAMA (r = 0.301, p = 0.012), SAS (r = 0.246, p = 0.015), HAMD (r = 0.252, p = 0.038) and BDI (r = 0.233, p = 0.022) with Pearson correlation analysis. Social Support Rating Scale (SSRS) had negative correlation with SAS (r = -0.244, p = 0.015) and BDI (r = -0.365, p = 0.000). Conclusion: This trial found that n-3 PUFAs supplementation in favor of venlafaxine alleviated the anxiety symptoms rather than depressive symptoms at the early stage of treatment (4 weeks) for first-diagnosed, drug-naïve depressed patients. However, the advantage disappeared in long-term treatment. Furthermore, childhood abuse and social support are closely related to the clinical and biological characteristics of depression. Both childhood trauma and lack of social support might be predictors of poor prognosis in depression. Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT03295708].

Carnitine and Depression.

Depression has become one of the most common mental diseases in the world, but the understanding of its pathogenesis, diagnosis and treatments remains insufficient. Carnitine is a natural substance that exists in organisms, which can be synthesized in vivo or supplemented by intake. Relationships of carnitine with depression, bipolar disorder and other mental diseases have been reported in different studies. Several studies show that the level of acylcarnitines (ACs) changes significantly in patients with depression compared with healthy controls while the supplementation of acetyl-L-carnitine is beneficial to the treatment of depression. In this review, we aimed to clarify the effects of ACs in depressive patients and to explore whether ACs might be the biomarkers for the diagnosis of depression and provide new ideas to treat depression.

Children With Food Allergy Are at Risk of Lower Lung Function on High-Pollen Days.

BACKGROUND: Grass pollen exposure is a risk factor for childhood asthma hospital attendances. However, its short-term influence on lung function, especially among those with other allergic conditions, has been less well-studied. OBJECTIVE: To investigate this association in a population-based sample of children. METHODS: Within the HealthNuts cohort, 641 children performed spirometry during the grass pollen season. Grass pollen concentration was considered on the day of testing (lag 0), up to 3 days before (lag 1-lag 3), and cumulatively (lag 0-3). We used linear regression to assess the relevant associations and examined potential interactions with current asthma, hay fever or eczema, and food allergy. RESULTS: Associations were observed only in children with allergic disease (P value for interaction ≤ 0.1). In children with food allergy, grass pollen concentration was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) and lower mid-forced expiratory flows (FEF25%-75%) at all lags (eg, at lag 2, FEV1/FVC z-score = -0.50 [95% CI -0.80 to -0.20] and FEF25%--75% z-score = -0.40 [-0.60 to -0.04] per 20 grains/m3 pollen increase), and increased bronchodilator responsiveness (BDR) at lag 2 and lag 3 (eg, at lag 2, BDR = (31 [95% CI -0.005 to 62] mL). In children with current asthma, increasing grass pollen concentration was associated with lower FEF25%-75% and increased BDR, whereas children with current hay fever or eczema had increased BDR only. CONCLUSIONS: A proactive approach needs to be enforced to manage susceptible children, especially those with food allergy, before high-grass pollen days.

The association between outdoor allergens - pollen, fungal spore season and high asthma admission days in children and adolescents.

Periods when asthma admissions peaks have serious implications for asthma sufferers and hospitals. We assessed the association between aeroallergen exposure and childhood asthma peak periods during two grass pollen seasons using the Melbourne Air Pollen Children and Adolescent Health (MAPCAH) study conducted in Melbourne, Australia. Two peak periods were identified. Effect modifications by atopy and sex were considered. All pollen 2 days prior was associated with increased odds of these peak periods. Same day fungal spores, but not pollen, were important. Grass at lag 2 was associated with increased odds 1.03 (95%CI 1.01, 1.05) as was the same day Alternaria 1.02 (1.00, 1.04) per spore/m3 for boys. In addition to pollen, fungal spores particularly Alternaria may result in days of high exacerbations during pollen seasons. Further guidance is needed to better prepare families/carers with information about the increased risk of asthma attacks in children prior to pollen seasons.

Associations between grass pollen exposures in utero and in early life with food allergy in 12-month-old infants.

Birth during pollen seasons may influence food allergy risk but no study has assessed pollen exposure. Using the HealthNuts population-based cohort of 5276 infants, we assessed grass pollen exposures, in utero and up to the first 6 months of life, on hen's egg, sesame and peanut allergy outcomes at 12 months. Cumulative pollen exposure in the first 7 days of life increased risk of peanut sensitization aMOR (adjusted multinomial odds ratio) = 1.21 (95% CI: 1.01-1.44). Exposure between first 4-6 months of life increased risk of hen's egg aMOR = 1.02 (95% CI: 1.004-1.04) and sensitization to all foods aMOR = 1.02 (95% CI: 1.003-1.04). Grass pollen exposure was associated with food challenge diagnosed food allergy, but only among infants with a maternal history of food allergy. Exposure to grass pollen in the intrauterine period and infancy may be important but more studies are needed to replicate these findings.

The maternal gut microbiome during pregnancy and offspring allergy and asthma.

Environmental exposures during pregnancy that alter both the maternal gut microbiome and the infant's risk of allergic disease and asthma include a traditional farm environment and consumption of unpasteurized cow's milk, antibiotic use, dietary fiber, and psychosocial stress. Multiple mechanisms acting in concert may underpin these associations and prime the infant to acquire immune competence and homeostasis following exposure to the extrauterine environment. Cellular and metabolic products of the maternal gut microbiome can promote the expression of microbial pattern recognition receptors, as well as thymic and bone marrow hematopoiesis relevant to regulatory immunity. At birth, transmission of maternally derived bacteria likely leverages this in utero programming to accelerate postnatal transition from a TH2- to TH1- and TH17-dominant immune phenotype and maturation of regulatory immune mechanisms, which in turn reduce the child's risk of allergic disease and asthma. Although our understanding of these phenomena is rapidly evolving, the field is relatively nascent, and we are yet to translate existing knowledge into interventions that substantially reduce disease risk in humans. Here, we review evidence that the maternal gut microbiome impacts the offspring's risk of allergic disease and asthma, discuss challenges and future directions for the field, and propose the hypothesis that maternal carriage of Prevotella copri during pregnancy decreases the offspring's risk of allergic disease via production of succinate, which in turn promotes bone marrow myelopoiesis of dendritic cell precursors in the fetus.

Study protocol of a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg oral immunotherapy at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo (Probiotic Egg Allergen Oral Immunotherapy for Treatment of Egg Allergy: PEAT study).

INTRODUCTION: Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo. METHODS AND ANALYSIS: 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms-probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12619000480189.

Effects of maternal deprivation stress and maternal dietary of n-3 polyunsaturated fatty acids on the neurobehavioral development of male offspring.

Objectives: Early-life stress and polyunsaturated fatty acids (PUFAs) have profound effects on brain development. Polyunsaturated fatty acids (PUFAs) are essential nutrients and normal components for development. The aims of this study are to investigate the effects of maternal deprivation (MD) stress and maternal dietary of n-3 PUFAs on the physical and neurobiological developments of offspring.Methods: According to the content of n-3 PUFAs in diets, female dams were divided into three groups (n = 6-7): deficiency, control and supplementary. MD paradigm was performed 6 h a day from postnatal days (PND) 1 to PND 14. The physical parameters and neurobehavioral tests were measured.Results: Different effects of MD stress, maternal diet and time on physical and neurobehavioral developments were observed. There was an interaction among stress, diet and time on body weight. MD stress markedly decreased weight among different diet groups, while deficiency diet significantly increased weight on PND 21 in N-MD pups and on PND 14 in MD pups. Moreover, MD stress delayed fur appearance and eye opening, whereas deficiency diet accelerated eye opening. On cliff avoidance and rearing frequency, MD pups performed worse; however a subtle delay on the surface righting was observed in supplementary group. Additionally, MD pups performed worse on PND 14 in forelimb grip. Unfortunately, there were no significant effects on incisor eruption, locomotion frequency and negative geotaxis.Discussion: This study suggests that early MD and inadequate intake of n-3 PUFAs are harmful to optimal growth and neurobehavioral development.

Is short-term exposure to grass pollen adversely associated with lung function and airway inflammation in the community?

BACKGROUND: The association between grass pollen exposure and early markers of asthma exacerbations such as lung function changes and increase in airway inflammation is limited. We investigated the associations between short-term grass pollen exposure and lung function and airway inflammation in a community-based sample, and whether any such associations were modified by current asthma, current hay fever, pollen sensitization, age, and other environmental factors. METHODS: Cross-sectional and short-term analyses of data from the Melbourne Atopy Cohort Study (MACS) participants (n = 936). Lung function was assessed using spirometry. Airway inflammation was assessed by fractional exhaled nitric oxide (FeNO) and exhaled breath condensate pH and nitrogen oxides (NOx). Daily pollen counts were collected using a volumetric spore trap. The associations were examined by linear regression. RESULTS: Higher ambient levels of grass pollen 2 days before (lag 2) were associated with lower mid-forced expiratory flow (FEF25%-75% ) and FEV1 /FVC ratio (Coef. [95% CI] = -119 [-226, -11] mL/s and -1.0 [-3.0, -0.03] %, respectively) and also 3 days before (lag 3). Increased levels of grass pollen a day before (lag 1) were associated with increased FeNO (4.35 [-0.1, 8.7] ppb) and also at lag 2. Adverse associations between pollen and multiple outcomes were greater in adults with current asthma, hay fever, and pollen sensitization. CONCLUSION: Grass pollen exposure was associated with eosinophilic airway inflammation 1-2 days after exposure and airway obstruction 2-3 days after exposure. Adults and individuals with asthma, hay fever, and pollen sensitization may be at higher risk.

Plasma metabolomic profiles associated with infant food allergy with further consideration of other early life factors.

BACKGROUND: Fatty acids have been implicated in early life immune development. Food allergy provides a clear phenotype of early allergic disease. Fish oil and vitamin D have immune-modulating properties. We aimed to identify the metabolomic profile of (i) infant food allergy and (ii) factors linked to food allergy in past studies such as fish oil supplementation and serum 25OHD3 levels in early life. METHODS: NMR was used to quantify 73 metabolites in plasma of 1 year old infants from the Barwon Infant Study (n=485). Logistic regression models were used to examine associations between infant metabolome and food allergy in infants. Linear regression models were used to describe associations between maternal fish oil supplementation and 25OHD3 levels with infant metabolites. RESULTS: A higher linoleic acid: total fatty acid (FA) ratio and phenylalanine level were associated with higher odds of food allergy. Antenatal fish oil supplementation was positively associated with docosahexaenoic acid (DHA) and omega-3 related metabolite levels. Postnatal 25OHD3 levels at 1 year of age were positively associated with several FA measures and creatinine and inversely with the saturated FA: total FA ratio. Only the postnatal 25OHD3 patterns persisted after adjustment for multiple comparisons. CONCLUSIONS: Infants with food allergy had altered fatty acid profiles at one year. Fish oil supplementation in pregnancy was associated with higher DHA and omega-3 related metabolites at 1 year of age. Associations were modest and the most robustly altered metabolomic profiles were with postnatal 25OHD3 levels.

Neferine and lianzixin extracts have protective effects on undifferentiated caffeine-damaged PC12 cells.

BACKGROUND: The embryos of Nelumbo nucifera Gaertn seeds, lianzixin, are used in China as food and traditional herbal medicine. Principal therapeutic indications are insomnia, anxiety and pyrexia. Caffeine is a psychostimulant and excessive use predisposes to cell damage and neurotoxicity. We aimed to investigate the potential protect effect of Neferine and lianzixin extracts on undifferentiated caffeine-damaged phaeochromocytoma cells (PC12 cells). METHODS: A cell damage model based on undifferentiated PC12 was established with caffeine. Effect of Lianzixin extracts (total alkaloids, alcohol extract and water extract) and neferine on caffeine-damaged PC12 cells was evaluated. Cell viability was assessed using the methyl thiazolyl tetrazolium (MTT) assay, cellular morphology by inverted microscope, the nucleus by Hoechst 33342 staining and cleaved poly ADP-ribose polymerase (PARP) expression by western blot analysis. RESULTS: Lianzixin extracts (total alkaloids, alcohol extract and water extract) and neferine improved the viability of PC12 cells damaged by caffeine. The morphology of PC12 cells pretreated with neferine, or alcohol or water extract of lianzixin aggregated and attached better than caffeine-damaged cells, but cells pretreated with total alkaloids of lianzixin showed abnormal morphology. Compared with caffeine-damaged cells, cells pretreated with neferine, or alcohol or water extract of lianzixin showed a notable increase in nucleus staining and an obvious decrease in cleaved PARP expression. CONCLUSIONS: Lianzixin extracts and neferine have protective effects against caffeine-induced damage in PC12 cells, which laid a foundation for finding a new medicine value of Lianzixin.

Dietary of n-3 polyunsaturated fatty acids influence neurotransmitter systems of rats exposed to unpredictable chronic mild stress.

Emerging evidence suggest that neuromodulators are the critical factor involved in depression. This study aimed to investigate the effects of unpredictable chronic mild stress (CUMS) and n-3 polyunsaturated fatty acids (n-3 PUFAs) on central nervous system. The depressive-like behaviors induced by CUMS were assessed by sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to quantify the levels of neurotransmitters and their metabolites involved in serotonergic, dopaminergic, noradrenergic, GABAergic neurotransmitter systems in hippocampus and prefrontal cortex. Repeated CUMS caused depressive-like behaviors of rats, associated with the alteration of neurotransmitters in brain, including the decreasing DA level, the increasing NE and GABA level, and the increasing 5-HT turnover rate in hippocampus, which could be partly alleviated by sufficient n-3 PUFAs supplementation. The influence of stress and diet on neurotransmitters in the prefrontal cortex was slight. However, it was obvious that supplementary of n-3 PUFAs relieved the decreasing DA/NE between-metabolite ratio 1,2 and DA/5-HT between-metabolite ratio 1,2 in the prefrontal cortex caused by CUMS. Altered neurotransmitter turnover rates and between-metabolite ratios in brain may be better predictors in depression and antidepressant treatment compared with monoamine neurotransmitters.

Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia.

Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.

The status of ω-3 PUFAs influence chronic unpredicted mild stress-induced metabolic side effects in rats through INSIG/SREBP pathway.

Metabolic disturbances, including lipid metabolism, bone metabolism, and glycometabolism, are common in depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which are reported to possess antidepressant effect, have also been shown to regulate metabolism. To further clarify the potential link between ω-3 PUFAs and stress-induced metabolic disturbances, metabolic-related parameters including body weight, visceral fat, fatty acid composition and serum parameters, such as serum lipids, free fatty acid (FFA), glucose (GLU), calcium and phosphorus in rats were measured. Moreover, hepatic insulin induced gene (INSIG)/sterol regulatory element binding protein (SREBP) pathway was also investigated. After 5 weeks of chronic unpredicted mild stress (CUMS) administration, rats were induced to a depressive-like state and exhibited decreased serum high-density lipoprotein (HDL-c), body weight and visceral fat, accompanied by altered C18:2n6c and ω-3/ω-6 PUFAs. Supplement of ω-3 PUFAs showed robust antidepressant effects and has beneficial effects on lipid profile. On the contrary, ω-3 PUFAs deficiency induced the visceral fat accumulation and decreased the serum calcium and phosphorus in stressed rats. Additionally, CUMS significantly increased hepatic expressions of SREBP-cleavage activating protein (SCAP)/SREBP-1 and decreased the expression of INSIG-1. This disturbance of SREBPs system is aggravated by ω-3 PUFAs deficiency and alleviated by ω-3 PUFAs supplementation. This study discloses the novel findings that ω-3 PUFAs deficiency will exacerbate the metabolic disturbances in stressed rats. Furthermore, supplementation of ω-3 PUFAs on individuals with a high risk of depression might be an effective way to prevent metabolic disorders accompanied by depression with the involvement of INSIG/SREBP pathway.