Omega-3 and Omega-6 fatty acids and risk of psychotic outcomes in the ALSPAC birth cohort.

BACKGROUND: Long chain polyunsaturated fatty acid (PUFA) levels have been implicated in the pathology of psychotic disorders. We investigated the relationship between childhood PUFA levels and later psychotic experiences (PE's) in a large birth cohort. METHODS: Plasma levels of Ω-3 and Ω-6 fatty acids (FA's) were assayed at ages 7 and 16 years. PE's were assessed at ages 12 and 18 years using a semi-structured interview. Primary outcome was any PE's at 18 years; sensitivity analyses examined incident PE's between ages 12 and 18 years, persistent PE's (at 12 and 18) and psychotic disorder at 18 years. Genetic instruments for Ω-3 and Ω-6 were derived and used in a multivariable Mendelian Randomization analysis. RESULTS: Higher levels of Ω-6 FA's AA, OA and AdA at age 7 years were weakly associated with a reduced risk for PE's at 18 years, however, effect sizes were small and attenuated after adjusting for confounders (strongest evidence for OA; adjusted OR, 0.842; 95% CI, 0.711, 0.998; p, 0.048). Total Ω-6 levels at age 16 years were associated with an increased odds of psychotic disorder at age 18 years. However, there was no association between Ω-6/Ω-3 ratio and psychosis outcomes, nor with genetic instruments of total Ω-3 or Ω-6 levels. CONCLUSIONS: There is no strong evidence that total plasma Ω-3 FA levels or Ω-6/Ω-3 ratios in childhood and mid-adolescence are associated with increased risk for PE's or psychotic disorder, but very marginal evidence that alterations in the Ω-6 pathway at developmental time points might influence risk2.

Lipids and polyunsaturated fatty acid levels in deliberate self-harm: a 10-year follow-up study.

OBJECTIVES: To evaluate if n-3 polyunsaturated fatty acids (PUFAs) and lipid levels are associated with episodes of self-harm or depression over a 10-year period. METHODS: We included 40 individuals who self-harmed and 40 controls. Episodes of self-harm and depression were ascertained and levels of depression, impulsivity, suicidal ideation and plasma lipid levels measured at baseline and at 10-year follow-up. RESULTS: Further episode(s) of self-harm occurred in 26% of cases. Omega-3 PUFAs or lipids were not predictive of depressive or self-harm episodes. Baseline eicosapentaenoic acid levels were modestly correlated with suicidal ideation at follow-up and dihomo-γ-linolenic acid and arachidonic acid were modestly correlated with motor impulsivity at follow-up in cases. CONCLUSIONS: Despite significant negative correlations at baseline between plasma lipids, n-3 PUFAs and psychopathology, these levels were not predictive of clinical outcome over a 10-year period. Further research however is required due to the relatively low sample size and the risk of selection bias due to loss to follow-up in this study.

Distribution of omega-6 and omega-3 polyunsaturated fatty acids in the whole rat body and 25 compartments.

The steady state compositions of omega-6 and omega-3 polyunsaturated fatty acids (PUFA) throughout the various viscera and tissues within the whole body of rats have not previously been described in a comprehensive manner. Dams consumed diets containing 10wt% fat (15% linoleate and 3% α-linolenate). Male offspring (n=9) at 7-week of age were euthanized and dissected into 25 compartments. Total lipid fatty acids for each compartment were quantified by GC/FID and summed for the rat whole body; total n-6 PUFA was 12wt% and total n-3 PUFA was 2.1% of total fatty acids. 18:2n-6 accounted for 84% of the total n-6 PUFA, 20:4n-6 was 12%, 18:3n-3 was 59% of the total n-3 PUFA, 20:5n-3 was 2.1%, and 22:6n-3 was 32%. The white adipose tissue contained the greatest amounts of 18:2n-6 (1.5g) and 18:3n-3 (0.2g). 20:4n-6 was highest in muscle (60mg) and liver (57mg), while 22:6n-3 was greatest in muscle (46mg), followed by liver (27mg) and carcass (20mg). In terms of fatty acid composition expressed as a percentage, 18:2n-6 was the highest in the heart (13wt%), while 18:3n-3 was about 1.3wt% for skin, white adipose tissue and fur. 20:4n-6 was highest (21-25wt%) in the circulation, kidney, and spleen, while 22:6n-3 was highest in the brain (12wt%), followed by the heart (7.9wt%), liver (5.9wt%), and spinal cord (5.1wt%). Selectivity was greatest when comparing 22:6n-3 in brain (12%) to white adipose (0.08%) (68-fold) and 22:5n-6 in testes (15.6%) compared to white adipose (0.02%), 780-fold.

Association of selenium and copper with lipids in umbilical cord blood.

Altered levels of selenium and copper have been linked with altered cardiovascular disease risk factors including changes in blood triglyceride and cholesterol levels. However, it is unclear whether this can be observed prenatally. This cross-sectional study includes 274 singleton births from 2004 to 2005 in Baltimore, Maryland. We measured umbilical cord serum selenium and copper using inductively coupled plasma mass spectrometry. We evaluated exposure levels vis-à-vis umbilical cord serum triglyceride and total cholesterol concentrations in multivariable regression models adjusted for gestational age, birth weight, maternal age, race, parity, smoking, prepregnancy body mass index, n-3 fatty acids and methyl mercury. The percent difference in triglycerides comparing those in the highest v. lowest quartile of selenium was 22.3% (95% confidence interval (CI): 7.1, 39.7). For copper this was 43.8% (95% CI: 25.9, 64.3). In multivariable models including both copper and selenium as covariates, copper, but not selenium, maintained a statistically significant association with increased triglycerides (percent difference: 40.7%, 95% CI: 22.1, 62.1). There was limited evidence of a relationship of increasing selenium with increasing total cholesterol. Our findings provide evidence that higher serum copper levels are associated with higher serum triglycerides in newborns, but should be confirmed in larger studies.

Cultural symbolism of fish and the psychotropic properties of omega-3 fatty acids.

Fish is a food with unique psychotropic properties. Consumption of long-chain omega-3 fatty acids, rich in seafood, reduces depression, aggression and anger while improving mental well-being. We posit that symbols of fish have become linked to the emotional states induced by long-chain fatty acid by associative pairings, both conscious and unconscious. The limbic and hippocampal activity necessary for memory formation containing emotional content and the labeling of social context by cortical processes appears to be optimized by diets rich in long-chain omega-3 fatty acid. In this critical literature survey, we find that fish have been culturally labeled as symbols of emotional well-being and social healing in religious and medical practices among independent cultures, for at least six millennia. This understanding of the perception of fish as a symbolically healing or purifying food can assist current messages improving public health.

Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls.

Deficiency in the long-chain omega-3 fatty acid, docosahexaenoic acid (DHA) has been associated with increased corticotropin releasing hormone and may contribute to hypothalamic pituitary axis (HPA) hyperactivity. Elevated levels of the neuroactive steroids, allopregnanolone (3alpha,5alpha-THP) and 3alpha,5alpha-tetrahydrodeoxycorticosterone (THDOC) appear to counter-regulate HPA hyperactivity. Plasma essential fatty acids and neurosteroids were assessed among 18 male healthy controls and among 34 male psychiatric patients with DSM-III alcoholism, depression, or both. Among all subjects, lower plasma DHA was correlated with higher plasma THDOC (r = -0.3, P < 0.05) and dihydroprogesterone (DHP) (r = -0.52, P < 0.05). Among psychiatric patients lower DHA was correlated with higher DHP (r = -0.60, P < 0.01), and among healthy controls lower plasma DHA was correlated with higher THDOC (r = -0.83, P < 0.01) and higher isopregnanolone (3beta,5alpha-THP) (r = -0.55, P < 0.05). In this pilot observational study, lower long-chain omega-3 essential fatty acid status was associated with higher neuroactive steroid concentrations, possibly indicating increased feedback inhibition of the HPA axis.

CT appearance of incidental pancreatic lipomas: a case series.

Pancreatic lipomas are rare benign lesions, with only 15 examples documented in the current literature. We describe five cases of intrapancreatic lipomas from a single institution, all incidentally found using computed tomography within a 14-month period. Computed tomography depicted lipomas as homogeneous, nonenhancing, well-marginated lesions with a density coefficient consistent with adipose tissue.

Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression.

OBJECTIVE: Postpartum depression (PPD) affects 10-15% of mothers. Omega-3 fatty acids are an intriguing potential treatment for PPD. METHOD: The efficacy of omega-3 fatty acids for PPD was assessed in an 8-week dose-ranging trial. Subjects were randomized to 0.5 g/day (n = 6), 1.4 g/day (n = 3), or 2.8 g/day (n = 7). RESULTS: Across groups, pretreatment Edinburgh Postnatal Depression Scale (EPDS) and Hamilton Rating Scale for Depression (HRSD) mean scores were 18.1 and 19.1 respectively; post-treatment mean scores were 9.3 and 10.0. Percent decreases on the EPDS and HRSD were 51.5% and 48.8%, respectively; changes from baseline were significant within each group and when combining groups. Groups did not significantly differ in pre- or post-test scores, or change in scores. The treatment was well tolerated. CONCLUSION: This study was limited by small sample size and lack of placebo group. However, these results support further study of omega-3 fatty acids as a treatment for PPD.

The relationship between folate and docosahexaenoic acid in men.

OBJECTIVE: Docosahexaenoic acid (DHA, 22:6n-3), an essential omega 3 fatty acid, may protect against disorders of emotional regulation as well as cardiovascular disease. Animal studies demonstrate that dietary folate can increase tissue concentrations of DHA, although the literature, to date, includes no human studies examining the possibility that folate status may affect plasma DHA concentrations. The objective of this study is to determine if the blood concentrations of folate and DHA are correlated in humans. DESIGN: Retrospective study. SETTING: An American research hospital. SUBJECTS: A total of 15 normal and 22 hostile and aggressive subjects, with a mean age of 38 years. METHODS: Concentrations of plasma polyunsaturated essential fatty acids and red blood cell folate (RBC folate) were obtained prior to 1996, before American flour was enriched with folate. RESULTS: RBC folate was significantly correlated with plasma DHA, r=0.57, P=0.005 in the aggressive group. Age, smoking and alcohol consumption did not alter the results. No other essential fatty acids were significantly associated with RBC folate in either group. CONCLUSIONS: The positive relationship between plasma DHA and RBC folate concentrations suggests that these two nutrients should be examined together in order to make the most accurate inferences about their relative contributions to disease pathogenesis. Our findings present one explanation why some conditions associated with hostility and low DHA status, such as cardiovascular disease and emotional disorders, are also associated with low folate status. SPONSORSHIP: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism.

Dietary intake of n-3, n-6 fatty acids and fish: relationship with hostility in young adults--the CARDIA study.

BACKGROUND: Hostility has been shown to predict both the development and manifestation of coronary disease. Examining the inter-relation of dietary intake of fish and of polyunsaturated (n-3 and n-6) essential fatty acids with hostility may provide additional insights into the cardioprotective effect of dietary fish and polyunsaturated fatty acids. OBJECTIVE: To examine the association of dietary n-3, n-6 fatty acids and fish with level of hostility in a sample of 3581 urban white and black young adults. DESIGN: Cross-sectional observational study as part of an ongoing cohort study. A dietary assessment in 1992-1993 and measurement of hostility and other covariates in 1990-1991 were used in the analysis. RESULTS: The multivariate odds ratios of scoring in the upper quartile of hostility (adjusting for age, sex, race, field center, educational attainment, marital status, body mass index, smoking, alcohol consumption and physical activity) associated with one standard deviation increase in docosahexaenoic acid (DHA, 22:6) intake was 0.90 (95% CI=0.82-0.98; P=0.02). Consumption of any fish rich in n-3 fatty acids, compared to no consumption, was also independently associated with lower odds of high hostility (OR=0.82; 95% CI=0.69-0.97; P=0.02). CONCLUSIONS: These results suggest that high dietary intake of DHA and consumption of fish rich in n-3 fatty acids may be related to lower likelihood of high hostility in young adulthood. The association between dietary n-3 fatty acids and hostile personality merits further research.

A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia.

OBJECTIVE: This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid (EPA) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder. METHOD: Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were randomly assigned to receive either 3 g/day of ethyl EPA (N=43) or placebo (N=44) in a 16-week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 1, 2, 4, 8, 12, and 16; a cognitive battery was administered at baseline and at week 16. RESULTS: No differences were found between groups in positive or negative symptoms, mood, cognition, or global impression ratings. Results were similar for the intention-to-treat (N=87) and completer (N=75) groups. CONCLUSIONS: For schizophrenia patients treated with 3 g/day of ethyl EPA, improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo.

Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans.

A physiological compartmental model of alpha-linolenic acid metabolism was derived from the plasma concentration-time curves for d5-18:3n-3, d5-20:5n-3, d5-22:5n-3, and d5-22:6n-3 in eight healthy subjects. Subjects received a 1-g oral dose of an isotope tracer of alpha-linolenate (d5-18:3n-3 ethyl ester) while subsisting on a rigorously controlled beef-based diet. By utilizing the Windows Simulation and Analysis Modeling program, kinetic parameters were determined for each subject. Half-lives and mean transit times of the n-3 fatty acids in the plasma were also determined. The model predicted plasma values for the n-3 fatty acids in good accordance with the measured steady state concentrations and also predicted dietary linolenic acid intake for each subject in accordance with values determined by lipid analysis of the diet. Only about 0.2% of the plasma 18:3n-3 was destined for synthesis of 20:5n-3, approximately 63% of the plasma 20:5n-3 was accessible for production of 22:5n-3, and 37% of 22:5n-3 was available for synthesis of 22:6n-3. The inefficiency of the conversion of 18:3n-3 to 20:5n-3 indicates that the biosynthesis of long-chain n-3 PUFA from alpha-linolenic acid is limited in healthy individuals. In contrast, the much greater rate of transfer of mass from the plasma 20:5n-3 compartment to 22:5n-3 suggests that dietary eicosapentaenoic acid may be well utilized in the biosynthesis of 22:6n-3 in humans.

Fish consumption and depressive symptoms in the general population in Finland.

Fish contains high concentrations of omega-3 polyunsaturated fatty acids. Several studies have reported depletions of omega-3 fats among depressed patients, and a cross-national comparison has revealed a significant inverse correlation between annual prevalence of major depression and fish consumption. In a sample of 3,204 Finnish adults, depressive symptoms were estimated with the Beck Depression Inventory. A frequency question was used to measure fish consumption. Multiple logistic regression analysis was conducted to assess the association between depression and fish consumption. After the analysis adjusted for potential confounders, the likelihood of having depressive symptoms was significantly higher among infrequent fish consumers than among frequent consumers.

Lactate-induced rage and panic in a select group of subjects who perpetrate acts of domestic violence.

BACKGROUND: Perpetrators of domestic violence frequently report symptoms of autonomic arousal and a sense of fear and/or loss of control at the time of the violence. Since many of these symptoms are also associated with panic attacks, we hypothesized that perpetrators of domestic violence and patients with panic attacks may share similar exaggerated fear-related behaviors. To test this hypothesis, we employed the panicogenic agent sodium lactate to examine the response of perpetrators to anxiety fear induced by a chemical agent. METHODS: Using a double-blind, placebo-controlled design, we infused 0.5 mol/L sodium lactate or placebo over 20 min on separate days to a select group of subjects who perpetrate acts of domestic violence and two nonviolent comparison groups. We compared their behavioral, neuroendocrine, and physiologic responses. RESULTS: Lactate administration elicited intense emotional responses in the perpetrators of domestic violence. Perpetrators evidenced more lactate-induced rage and panic and showed greater changes in speech, breathing, and motor activity than did nonviolent control subjects. There were no significant differences between the groups for any neuroendocrine or physiologic measure. CONCLUSIONS: These results are consistent with our hypothesis that some perpetrators of domestic violence have exaggerated fear-related behavioral responses.

Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia.

Recent research suggests that deficient uptake or excessive breakdown of membrane phospholipids may be associated with schizophrenia. We review available clinical research on abnormalities in membrane fatty acid composition and metabolism in schizophrenia, and therapeutic trials of fatty acid in this disorder. All potentially relevant English-language articles were identified from the medical and psychiatric literature with the aid of computer searches using key words such as lipids, phospholipids, prostaglandins and schizophrenia. All studies which include human subjects are reviewed. Empirical studies related to membrane hypotheses of schizophrenia focus on: 1) assessment of prostaglandins (PG) and their essential fatty acid (EFA) precursors in the tissues of patients with schizophrenia; 2) evaluation of the niacin flush test as a possible diagnostic marker; 3) evaluation of phospholipase enzyme activity; 4) NMR spectroscopy studies of brain phospholipid metabolism; and 5) therapeutic trials of PG precursors for the treatment of schizophrenia. The most consistent clinical findings include red blood cell fatty acid membrane abnormalities, NMR spectroscopy evidence of increased phospholipid turnover and a therapeutic effect of omega-3 fatty acid supplementation of neuroleptic treatment in some schizophrenia patients. Studies of EFA metabolism have proved fruitful for generating and testing novel etiologic hypotheses and new therapeutic agents for schizophrenia. Greater attention to factors that influence tissue EFA levels such as diet, tobacco and alcohol are required to reconcile inconsistent findings. Treatment studies, although promising, require independent replication.