A 52-week prophylactic randomised control trial of omega-3 polyunsaturated fatty acids in bipolar disorder.

OBJECTIVES: Previous work suggests supplementation with omega-3 polyunsaturated fatty acids (PUFAs) may improve mood symptoms in bipolar disorder (BD) although findings remain unclear. In this study, we assess the efficacy of omega-3 PUFA administration for prophylaxis in BD using a clinical trial design over 52-weeks (ClinicalTrials.gov Identifier: NCT04210804). METHODS: Individuals with BD (n = 80) were randomised to receive placebo (n = 40) or 1 g eicosapentaenoic acid (EPA) plus 1 g docosahexaenoic acid (DHA; n = 40) adjunctively for 52-weeks. The primary outcome measure comprised the number of mood episode relapses including hospital admissions and medication changes experienced. Secondary outcome measures included time to first mood episode relapse and change in psychometric measures of depression and elation (Hamilton Depression Rating Scale and Young Mania Rating Scale). RESULTS: No significant differences in the number of mood episode relapses (U = 490.00, p = 0.14) or the number of individuals requiring admission to hospital (χ2  = 0.67, p = 0.41) or medication adjustment in the omega-3 PUFA compared to the placebo group were noted. Time to relapse was not significantly different between groups (Log Rank χ2  = 0.41, p = 0.52). Change in Young Manic Rating Scale (F(3.12, 152.86) = 2.71, p = 0.05) was significantly different between treatment groups over 12-months, with scores at 9-months and 12-months significantly lower than those at 3-months in the omega-3 group and not in the placebo group. Change in Hamilton Depression Rating Scale, Global Clinical Impression and Global Assessment of Functioning were not different between groups. CONCLUSIONS: Despite a minor reduction in hypomania scores in the omega-3 PUFA group compared to placebo, we find little evidence that the supplementation of omega-3-PUFAs exhibits prophylactic benefit in BD.

Brain PUFA Concentrations Are Differentially Affected by Interactions of Diet, Sex, Brain Regions, and Phospholipid Pools in Mice.

BACKGROUND: PUFAs play vital roles in the development, maintenance, and functioning of circuitries that regulate reward and social behaviors. Therefore, modulations in PUFA concentrations of these brain regions may disrupt reward and social circuitries contributing to mood disorders, developmental disabilities, and addictions. Though much is known about regional and phospholipid-pool-specific PUFA concentrations, less is known about the effects of dietary interventions that concurrently lowers n-6 PUFA and supplements n-3 PUFA, on brain PUFA concentrations. There is even less knowledge on the effects of sex on brain PUFA concentrations. OBJECTIVE: This study aimed to comprehensively examine the interaction effects of diet (D), sex (S), brain regions (BR), and phospholipid pools (PL) on brain PUFA concentrations. METHODS: Male and female C57BL/6J mice were fed 1 of 4 custom-designed diets varying in linoleic acid (LNA) (8 en% or 1 en%) and eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) (0.4 en% or 0 en%) concentrations from in utero to 15 weeks old. At 15 weeks old, the prefrontal cortex, dorsal striatum, and cerebellum were collected. Fatty acids of 5 major PL were quantified by GC-flame ionization detection. Repeated measures ANOVA was used to test for differences among the groups for D, S, BR, and PL. RESULTS: No significant 4-way interactions on PUFA concentrations. DHA, predominant n-3 PUFA, concentrations were dependent on significant D × BR × PL interactions. DHA concentration was not affected by sex. Arachidonic acid (ARA; predominant n-6 PUFA) concentrations were not dependent on 3-way interactions. However, significant 2-way D × PL, BR × PL, and D × Sinteractions affected ARA concentrations. Brain fatty acid concentrations were differentially affected by various combinations of D, S, BR, and PL interactions. CONCLUSION: Though DHA concentrations are not affected by sex, ARA concentrations are affected by interactions of the 4 variables examined. This study provides comprehensive references in the investigation of complex interactions between factors that affect brain PUFA concentrations in mice.

Omega-3 (ω-3) and social skills interventions for reactive aggression and childhood externalizing behavior problems: a randomized, stratified, double-blind, placebo-controlled, factorial trial.

BACKGROUND: While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline. METHODS: In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7-16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome. RESULTS: Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31. CONCLUSIONS: Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.

Maternal fish consumption during pregnancy and smoking behavioural patterns.

n-3 Highly unsaturated fatty acids (HUFA), are essential components of neuronal membranes and mediate a range of complex bioactive properties including gene expression, myelination, cell-signalling and dopaminergic function. Deficits in n-3 HUFA have been linked to increased risks for addictive disorders, thus we posited that lower fish consumption would be associated with greater risks for perinatal smoking among 9640 mothers enroled in the Avon Longitudinal Study of Parents and Children. We used univariable and multivariable regression models to examine relationships between self-reported prenatal dietary intakes of n-3 HUFA-rich foods (fish and shellfish) and maternal smoking; outcomes included cessation and the number of cigarettes smoked per d. Both before and during pregnancy, there was consistent evidence (P<0·001) of protective fish intake-smoking associations; relative to mothers reporting no fish consumption, those who reported some fish consumption (<340 g/week) and high fish consumption (340 g+/week) at 32 weeks of gestation showed lower likelihoods of smoking (adjusted P values <0·001). Respective OR for these relationships were 0·87 (95% CI 0·77, 0·97) and 0·73 (95% CI 0·61, 0·86). Although the prevalence of smoking diminished, from a high of 31·6% (pre-pregnancy) to a low of 18·7% (second trimester), the magnitude of fish intake-smoking associations remained stable following adjustment for confounders. These observations suggest that greater fish or n-3 HUFA consumption should be evaluated as an intervention to reduce or prevent smoking in randomised clinical trials.

Reductions of intimate partner violence resulting from supplementing children with omega-3 fatty acids: A randomized, double-blind, placebo-controlled, stratified, parallel-group trial.

Omega-3 supplementation has been found to reduce externalizing behavior in children. Reciprocal models of parent-child behavior suggest that improving child behavior could lead to improvements in parent behavior, however no study has examined whether omega-3 supplementation in children could reduce intimate partner violence or child maltreatment by their adult caregivers. In this randomized, double-blind, placebo-controlled, stratified, parallel group trial, a community sample of children were randomized to receive either a fruit drink containing 1 gm of omega-3 fats (Smartfish Recharge; Omega-3 group, n = 100) or the same fruit drink without omega-3's (Placebo group, n = 100). Child participants, adult caregivers, and research staff were blinded to group assignment. Adult caregivers reported inter-partner and child-directed physical assault and psychological aggression at baseline, 6 months (end of treatment) and 12 months (6 months post-treatment) using the Conflicts Tactics Scale. Caregivers of children in the omega-3 group reported long-term reductions in psychological aggression in a group × time interaction. Improvements in adult psychological aggression were correlated with improvements in child externalizing behavior scores. No differences were reported for child maltreatment. This study is the first to show that omega-3 supplementation in children can reduce inter-partner psychological aggression among adult caregivers not receiving supplements. Findings suggest that improving child behavior through omega-3 supplementation could have long-term benefits to the family system as a whole.

Maternal dietary patterns during pregnancy and intelligence quotients in the offspring at 8 years of age: Findings from the ALSPAC cohort.

Dietary intake during pregnancy may influence child neurodevelopment and cognitive function. This study aims to investigate the associations between dietary patterns obtained in pregnancy and intelligence quotients (IQ) among offspring at 8 years of age. Pregnant women enrolled in the Avon Longitudinal Study of Parents and Children completed a food frequency questionnaire at 32 weeks' gestation (n = 12,195). Dietary patterns were obtained by cluster analysis. Three clusters best described women's diets during pregnancy: "fruit and vegetables," "meat and potatoes," and "white bread and coffee." The offspring's IQ at 8 years of age was assessed using the Wechsler Intelligence Scale for Children. Models, using variables correlated to IQ data, were performed to impute missing values. Linear regression models were employed to investigate associations between the maternal clusters and IQ in childhood. Children of women who were classified in the meat and potatoes cluster and white bread and coffee cluster during pregnancy had lower average verbal (ß = -1.74; p < .001 and ß = -3.05; p < .001), performance (ß = -1.26; p = .011 and ß = -1.75; p < .001), and full-scale IQ (ß = -1.74; p < .001 and ß = -2.79; p < .001) at 8 years of age when compared to children of mothers in the fruit and vegetables cluster in imputed models of IQ and all confounders, after adjustment for a wide range of known confounders including maternal education. The pregnant women who were classified in the fruit and vegetables cluster had offspring with higher average IQ compared with offspring of mothers in the meat and potatoes cluster and white bread and coffee cluster.

Meat Consumption During Pregnancy and Substance Misuse Among Adolescent Offspring: Stratification of TCN2 Genetic Variants.

BACKGROUND: Reducing meat consumption is often advised; however, inadvertent nutritional deficiencies during pregnancy may result in residual neurodevelopmental harms to offspring. This study assessed possible effects of maternal diets in pregnancy on adverse substance use among adolescent offspring. METHODS: Pregnant women and their 13-year-old offspring taking part in a prospective birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), provided Food Frequency Questionnaire data from which dietary patterns were derived using principal components analysis. Multivariable logistic regression models including potential confounders evaluated adverse alcohol, cannabis, and tobacco use of the children at 15 years of age. RESULTS: Lower maternal meat consumption was associated with greater problematic substance use among 15-year-old offspring in dose-response patterns. Comparing never to daily meat consumption after adjustment, risks were greater for all categories of problem substance use: alcohol, odds ratio OR = 1.75, 95% CI = (1.23, 2.56), p < 0.001; tobacco use OR = 1.85, 95% CI = (1.28, 2.63), p < 0.001; and cannabis OR = 2.70, 95% CI = (1.89, 4.00), p < 0.001. Given the likelihood of residual confounding, potential causality was evaluated using stratification for maternal allelic variants that impact biological activity of cobalamin (vitamin B12) and iron. Lower meat consumption disproportionally increased the risks of offspring substance misuse among mothers with optimally functional (homozygous) variants (rs1801198) of the gene transcobalamin 2 gene (TCN2) which encodes the vitamin B12 transport protein transcobalamin 2 implicating a causal role for cobalamin deficits. Functional maternal variants in iron metabolism were unrelated to the adverse substance use. Risks potentially attributable to cobalamin deficits during pregnancy include adverse adolescent alcohol, cannabis, and tobacco use (14, 37, and 23, respectively). CONCLUSIONS: Lower prenatal meat consumption was associated with increased risks of adolescent substance misuse. Interactions between TCN2 variant status and meat intake implicate cobalamin deficiencies.

Blood fatty acid changes in healthy young Americans in response to a 10-week diet that increased n-3 and reduced n-6 fatty acid consumption: a randomised controlled trial.

Military personnel generally under-consume n-3 fatty acids and overconsume n-6 fatty acids. In a placebo-controlled, double-blinded study, we investigated whether a diet suitable for implementation in military dining facilities and civilian cafeterias could benefit n-3/n-6 fatty acid status of consumers. Three volunteer groups were provided different diets for 10 weeks. Control (CON) participants consumed meals from the US Military's Standard Garrison Dining Facility Menu. Experimental, moderate (EXP-Mod) and experimental-high (EXP-High) participants consumed the same meals, but high n-6 fatty acid and low n-3 fatty acid containing chicken, egg, oils and food ingredients were replaced with products having less n-6 fatty acids and more n-3 fatty acids. The EXP-High participants also consumed smoothies containing 1000 mg n-3 fatty acids per serving, whereas other participants received placebo smoothies. Plasma and erythrocyte EPA and DHA in CON group remained unchanged throughout, whereas EPA, DHA and Omega-3 Index increased in EXP-Mod and EXP-High groups, and were higher than in CON group after 5 weeks. After 10 weeks, Omega-3 Index in EXP-High group had increased further. No participants exhibited changes in fasting plasma TAG, total cholesterol, LDL, HDL, mood or emotional reactivity. Replacing high linoleic acid (LA) containing foods in dining facility menus with similar high oleic acid/low LA and high n-3 fatty acid foods can improve n-6/n-3 blood fatty acid status after 5 weeks. The diets were well accepted and suitable for implementation in group feeding settings like military dining facilities and civilian cafeterias.

Methyl mercury, but not inorganic mercury, associated with higher blood pressure during pregnancy.

Prior studies addressing associations between mercury and blood pressure have produced inconsistent findings; some of this may result from measuring total instead of speciated mercury. This cross-sectional study of 263 pregnant women assessed total mercury, speciated mercury, selenium, and n-3 polyunsaturated fatty acids in umbilical cord blood and blood pressure during labor and delivery. Models with a) total mercury or b) methyl and inorganic mercury were evaluated. Regression models adjusted for maternal age, race/ethnicity, prepregnancy body mass index, neighborhood income, parity, smoking, n-3 fatty acids and selenium. Geometric mean total, methyl, and inorganic mercury concentrations were 1.40µg/L (95% confidence interval: 1.29, 1.52); 0.95µg/L (0.84, 1.07); and 0.13µg/L (0.10, 0.17), respectively. Elevated systolic BP, diastolic BP, and pulse pressure were found, respectively, in 11.4%, 6.8%, and 19.8% of mothers. In adjusted multivariable models, a one-tertile increase of methyl mercury was associated with 2.83mmHg (0.17, 5.50) higher systolic blood pressure and 2.99mmHg (0.91, 5.08) higher pulse pressure. In the same models, an increase of one tertile of inorganic mercury was associated with -1.18mmHg (-3.72, 1.35) lower systolic blood pressure and -2.51mmHg (-4.49, -0.53) lower pulse pressure. No associations were observed with diastolic pressure. There was a non-significant trend of higher total mercury with higher systolic blood pressure. We observed a significant association of higher methyl mercury with higher systolic and pulse pressure, yet higher inorganic mercury was significantly associated with lower pulse pressure. These results should be confirmed with larger, longitudinal studies.

Dietary patterns by cluster analysis in pregnant women: relationship with nutrient intakes and dietary patterns in 7-year-old offspring.

Little is known about how dietary patterns of mothers and their children track over time. The objectives of this study are to obtain dietary patterns in pregnancy using cluster analysis, to examine women's mean nutrient intakes in each cluster and to compare the dietary patterns of mothers to those of their children. Pregnant women (n = 12 195) from the Avon Longitudinal Study of Parents and Children reported their frequency of consumption of 47 foods and food groups. These data were used to obtain dietary patterns during pregnancy by cluster analysis. The absolute and energy-adjusted nutrient intakes were compared between clusters. Women's dietary patterns were compared with previously derived clusters of their children at 7 years of age. Multinomial logistic regression was performed to evaluate relationships comparing maternal and offspring clusters. Three maternal clusters were identified: 'fruit and vegetables', 'meat and potatoes' and 'white bread and coffee'. After energy adjustment women in the 'fruit and vegetables' cluster had the highest mean nutrient intakes. Mothers in the 'fruit and vegetables' cluster were more likely than mothers in 'meat and potatoes' (adjusted odds ratio [OR]: 2.00; 95% Confidence Interval [CI]: 1.69-2.36) or 'white bread and coffee' (OR: 2.18; 95% CI: 1.87-2.53) clusters to have children in a 'plant-based' cluster. However the majority of children were in clusters unrelated to their mother dietary pattern. Three distinct dietary patterns were obtained in pregnancy; the 'fruit and vegetables' pattern being the most nutrient dense. Mothers' dietary patterns were associated with but did not dominate offspring dietary patterns.

Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid autacoids: Implications for idiopathic pain syndromes?

BACKGROUND: Chronic idiopathic pain syndromes are major causes of personal suffering, disability, and societal expense. Dietary n-6 linoleic acid has increased markedly in modern industrialized populations over the past century. These high amounts of linoleic acid could hypothetically predispose to physical pain by increasing the production of pro-nociceptive linoleic acid-derived lipid autacoids and by interfering with the production of anti-nociceptive lipid autacoids derived from n-3 fatty acids. Here, we used a rat model to determine the effect of increasing dietary linoleic acid as a controlled variable for 15 weeks on nociceptive lipid autacoids and their precursor n-6 and n-3 fatty acids in tissues associated with idiopathic pain syndromes. RESULTS: Increasing dietary linoleic acid markedly increased the abundance of linoleic acid and its pro-nociceptive derivatives and reduced the abundance of n-3 eicosapentaenoic acid and docosahexaenoic acid and their anti-nociceptive monoepoxide derivatives. Diet-induced changes occurred in a tissue-specific manner, with marked alterations of nociceptive lipid autacoids in both peripheral and central tissues, and the most pronounced changes in their fatty acid precursors in peripheral tissues. CONCLUSIONS: The present findings provide biochemical support for the hypothesis that the high linoleic acid content of modern industrialized diets may create a biochemical susceptibility to develop chronic pain. Dietary linoleic acid lowering should be further investigated as part of an integrative strategy for the prevention and management of idiopathic pain syndromes.

Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression.

BACKGROUND: Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings. AIMS: To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials. METHOD: A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo. RESULTS: Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G = 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression. CONCLUSIONS: Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.

Current evidence and future directions for research with omega-3 fatty acids and attention deficit hyperactivity disorder.

PURPOSE OF REVIEW: Nutritional insufficiencies of nutrients such as omega-3 highly unsaturated fatty acids (HUFAs), vitamins and minerals have been linked to suboptimal developmental outcomes including attention deficit hyperactivity disorder (ADHD). Although the predominant treatment is currently psychostimulant medications, randomized clinical trials with omega-3 HUFAs have reported small-to-modest effects in reducing symptoms of ADHD in children despite arguable individual methodological and design misgivings. RECENT FINDINGS: This review presents, discusses and critically evaluates data and findings from meta-analytic and systematic reviews and clinical trials published within the last 12 months. Recent trajectories of this research are discussed, such as comparing eicosapentaenoic acid and docosahexaenoic acid and testing the efficacy of omega-3 HUFAs as an adjunct to methylphenidate. Discussion includes highlighting limitations and potential future directions such as addressing variable findings by accounting for other nutritional deficiencies and behavioural food intolerances. SUMMARY: The authors conclude that given the current economic burden of ADHD, estimated in the region of $77 billion in the USA alone, in addition to the fact that a proportion of patients with ADHD are either treatment resistant, nonresponders or withdraw from medication because of adverse side-effects, the investigation of nonpharmacological interventions including omega-3 HUFAs in clinical practice warrants extrapolating.

Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial.

BACKGROUND: While limited evidence suggests that omega-3 supplementation may reduce antisocial behavior in children, studies have not reported on posttreatment follow-up and most treatment periods have been of short duration. This study tests the hypothesis that omega-3 supplementation over 6 months will reduce behavior problems in children both at the end of treatment and at 6 months post treatment. METHODS: In this randomized, double-blind, placebo-controlled, stratified, parallel-group trial, a community sample of 8-16 year old children were randomized into a treatment group (N = 100) and a placebo-control group (N = 100). The supplementation consisted of a fruit drink containing 1 g/day of omega-3 or a placebo consisting of the same fruit drink without omega-3. Participants, caregivers, and research assistants were blinded to group assignment. The primary outcome measures of externalizing and internalizing behavior problems were reported by both caregivers and their children in a laboratory setting at 0 months (baseline), 6 months (end of treatment) and 12 months (6 months post treatment), together with the secondary outcome measures of parental antisocial behavior. Data were analyzed on an intention-to-treat basis including all participants. TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/ct2/show/NCT02016079?term=mauritius&rank=2 RESULTS: Significant group × time interactions were observed with the treatment group showing long-term improvements in child behavior problems. The average posttreatment effect size was d = -.59. Effects were documented for parent reports, but with the exception of proactive and reactive aggression, child-report data were nonsignificant. Parents whose children took omega-3 showed significant posttreatment reductions in their own antisocial and aggressive behavior. This improvement in caregiver behavior partly mediated the improvements observed in child behavior. CONCLUSIONS: Findings provide initial evidence that omega-3 supplementation can produce sustained reductions in externalizing and internalizing behavior problems. Results are the first to report improvements in caregiver behavior, and to establish this improvement as a part-mechanism for the efficacy of omega-3.

Polyunsaturated fatty acid levels in blood during pregnancy, at birth and at 7 years: their associations with two common FADS2 polymorphisms.

Minor alleles of polymorphisms in the fatty acid desaturase (FADS) gene cluster have been associated with reduced desaturation of the precursor polyunsaturated fatty acids (FAs) in small studies. The effects of these polymorphisms during progressive developmental stages have not previously been reported. Data from blood samples for 4342 pregnant women, 3343 umbilical cords reflecting the newborn's blood supply and 5240 children aged 7 years were analysed to investigate the associations of polyunsaturated FAs with rs1535 and rs174575-two polymorphisms in the FADS2 gene. Strong positive associations were observed between the minor G allele for these two markers, especially rs1535, and the substrates linoleic (18:2n-6) and α-linolenic (18:3n-3) acid. Negative associations were observed for the more highly unsaturated FAs such as arachidonic acid (20:4n-6), timnodonic acid (EPA, 20:5n-3) and cervonic acid (DHA, 22:6n-3). Bivariable genetic associations using the mother and child genotypes suggested that the newborn metabolism had a greater capacity to synthesize the more highly unsaturated omega-6 FAs than the more highly unsaturated omega-3 FAs. Nevertheless, despite the immaturity of the neonate, there was evidence that synthesis of DHA was occurring. However, by 7 years, no associations were observed with the maternal genotype. This suggested that the children's FA levels were related only to their own metabolism with no apparent lasting influences of the in utero environment.

Polyunsaturated fatty acid associations with dopaminergic indices in major depressive disorder.

Dopaminergic function is thought to be altered in major depression and, in animal studies, is reduced in omega-3 polyunsaturated fatty acid (PUFA) deficiency states. Therefore we studied PUFAs and resting prolactin, a marker for dopaminergic tone, and cerebrospinal fluid homovanillic acid (HVA), the chief dopamine metabolite. In medication-free adults (n = 23) with DSM-IV major depressive disorder (MDD), we measured plasma phospholipid levels of omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the omega-6 PUFA arachidonic acid (AA), and plasma prolactin levels before and after administration of dl-fenfluramine (FEN). In a subset of patients (n = 14), cerebrospinal fluid levels of HVA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were obtained through lumbar puncture. Baseline prolactin was negatively correlated with omega-3 PUFAs (logDHA, F(1,21) = 20.380, p < 0.001; logEPA, F(1,21) = 10.051, p = 0.005) and positively correlated with logAA:DHA (F(1,21) = 15.263, p = 0.001), a measure of omega-6/omega-3 balance. LogDHA was negatively correlated with CSF HVA (Spearman's ρ = -0.675, p = 0.008) but not 5-HIAA (Spearman's ρ = -0.143, p = 0.626) after controlling for sex and HVA - 5-HIAA correlation. PUFAs did not predict the magnitude of the FEN-stimulated change in prolactin, considered to be a serotonin effect. The robust relationship of omega-3 PUFAs with dopaminergic but not serotonergic indices suggests that omega-6:omega-3 balance may impact depression pathophysiology through effects on the dopaminergic system.

Narcissism Is Not Associated With Success in U.S. Army Soldier Training.

INTRODUCTION: Narcissism has been studied for its role in leadership using various versions of the Narcissistic Personality Inventory (NPI). Narcissism is described as having a "dark and negative" side as well as a "positive or bright" side. The bright side of narcissism, in particular, has been studied for its role in leadership. In studies among military personnel in Finland and Hungary, the NPI has been associated with positive leadership traits. We assessed if measures of narcissistic personality were predictive of entrance to and graduation from the Army Ranger Course among United States (U.S.) Army personnel. MATERIALS AND METHODS: We included the NPI as one of the measures in the Ranger Resilience and Improved Performance on Phospholipid-bound Omega-3's (RRIPP-3) study. RRIPP-3 was a double-blind, placebo-controlled dietary supplement intervention trial at Fort Benning, GA, that enrolled 555 officers when they entered the U.S. Army Infantry Basic Officer Leadership Course (IBOLC) with the intention to complete the U.S. Ranger School. RRIPP-3 volunteer participants consumed eight dietary supplements daily containing 2.3 g of omega-3 (krill oil) or macadamia nut oil (control) over a 20-week period. Blood spot samples were collected to monitor intake compliance. Cognitive functioning, resilience, and mood were assessed at approximately 14 and 16 weeks. Dietary intake was also assessed. The 40-item, forced-choice NPI was included to assess if three factors of narcissism: Leadership/Authority, Grandiose/Exhibitionism, and Entitlement/Exploitativeness measures of narcissistic personality were associated with entrance to and graduation from the Army Ranger Course. RESULTS: Of the 555 soldiers enrolled in RRIPP-3, there were no statistically significant differences in the total NPI scores comparing U.S. Army IBOLC officers who enrolled (n = 225) versus did not enroll (n = 330, p = .649) or graduated (n = 95; versus did not graduate [n = 460, p = .451]) from the Ranger Course. None of the three-factor NPI subscales differed statistically comparing either enrollment in (p = .442, .510, and .589, respectively) or graduation from the Ranger Course (p = .814, .508, and .813, respectively). CONCLUSIONS: Although narcissism has been positively associated with military trainee success in other countries, we did not find an association between narcissism and trainee success among U.S. Army trainees, and accordingly the level of narcissism did not predict trainee success or failure.

ω-3 fatty acid intakes are inversely related to elevated depressive symptoms among United States women.

Evidence that depressive symptoms are inversely related to n-3 (ω-3) fatty acids is growing among United States adults. We assessed whether self-reported depressive symptoms were inversely associated with n-3 fatty acid intakes by using a cross-sectional study in 1746 adults (aged 30-65 y) in Baltimore City, MD (2004-2009). The 20-item Center for Epidemiologic Studies-Depression Scale (CES-D) was used, with a CES-D score ≥16 suggestive of elevated depressive symptoms (EDS). By using the mean of two 24-h dietary recalls, n-3 highly unsaturated fatty acids (HUFAs; ≥20 carbons), n-3 polyunsaturated fatty acids (PUFAs; ≥18 carbons), and plausible ratios with n-6 (ω6) fatty acids were estimated. EDS prevalence was 18.1% among men and 25.6% among women. In women, the uppermost tertile (tertile 3) of n-3 PUFAs (compared with tertile 1) was associated with reduced odds of EDS by 49%, with a substantial sex differential. The n-3 PUFA:n-6:PUFA ratio was inversely related to EDS among women (tertile 2 vs. tertile 1, OR: 0.74; 95% CI: 0.41, 1.32; tertile 3 vs. tertile 1, OR: 0.47; 95% CI: 0.27, 0.83). A similar pattern was noted for n-3 HUFA:n-6 HUFA among women. For CES-D subscales, n-3 PUFA (% of energy) was inversely related to somatic complaints, whereas positive affect was directly related to n-3 HUFA (% of energy; total population and among women), n-3 HUFA:n-6 HUFA (women), and n-3 HUFA:n-6 PUFA (total population and among women). In sum, among United States women, higher intakes of n-3 fatty acids [absolute (n-3) and relative to n-6 fatty acids (n-3:n-6)] were associated with lower risk of elevated depressive symptoms, specifically in domains of somatic complaints (mainly n-3 PUFAs) and positive affect (mainly n-3 HUFAs).

Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research.

Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; #2·5% of energy (en%)) and arachidonic acid (#60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA a-linolenic acid (ALA; $1·5 en%) and EPA þ DHA ($1000 mg/d). Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to #2·5 en% (median LA 2·45 (2·1, 3·1); P,0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P,0·001) and EPA þ DHA (1482 mg, (374, 2558), P,0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to #2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno-fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism.