Docosahexaenoic acid for selective prevention of posttraumatic stress disorder among severely injured patients: a randomized, placebo-controlled trial. Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa. Cognitive effects of polyunsaturated fatty acids in children with attention deficit hyperactivity disorder symptoms: a randomised controlled trial. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis omega-3 Fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Reduced Symptoms of Inattention after Dietary Omega-3 Fatty Acid Supplementation in Boys with and without Attention Deficit/Hyperactivity Disorder Combination of Omega-3 Fatty Acids and Valproic Acid in Treatment of Borderline Personality Disorder: A Follow-Up Study EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors Psychoeducational Psychotherapy and Omega-3 Supplementation Improve Co-Occurring Behavioral Problems in Youth with Depression: Results from a Pilot RCT Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids. Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism. A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia Omega-3 fatty acids in major depressive disorder: A preliminary double-blind, placebo-controlled trial The effects of eicosapentaenoic acid in tardive dyskinesia: A randomized, placebo-controlled trial Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: A randomized, double-blind, placebo-controlled trial A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia Comparison between the AA/EPA ratio in depressed and non depressed elderly females: omega-3 fatty acid supplementation correlates with improved symptoms but does not change immunological parameters Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder. Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial. The effect of docosahexaenoic acid-containing food administration on symptoms of attention-deficit/hyperactivity disorder—a placebo-controlled double-blind study Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study Short-term supplementation of acute long-chain omega-3 polyunsaturated fatty acids may alter depression status and decrease symptomology among young adults with depression: A preliminary randomized and placebo controlled trial Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Long chain omega 3 polyunsaturated fatty acids supplementation in the treatment of elderly depression: Effects on depressive symptoms, on phospholipids fatty acids profile and on health-related quality of life A pilot open case series of ethyl-EPA supplementation in the treatment of anorexia nervosa. Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. Combined ω3 and ω6 Supplementation in Children With Attention-Deficit Hyperactivity Disorder (ADHD) Refractory to Methylphenidate Treatment Effect of Omega-3 Fatty Acids Supplementation on Depressive Symptoms and on Health-Related Quality of Life in the Treatment of Elderly Women with Depression: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial Effects of omega-3 fatty acid supplementation on mood and emotional information processing in recovered depressed individuals A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism Effects of Omega-3 in the treatment of violent schizophrenia patients The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension. A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties Omega-3 Fatty Acid Augmentation of Citalopram Treatment for Patients With Major Depressive Disorder A Pilot Randomized Controlled Trial of Omega-3 Fatty Acids for Autism Spectrum Disorder Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among disaster medical assistance team members after the Great East Japan Earthquake: The APOP randomized controlled trial Inflammation as a Predictive Biomarker for Response to Omega-3 Fatty Acids in Major Depressive Disorder: A Proof of Concept Study n-3 Polyunsaturated Fatty Acids Decrease Anxiety Feelings in a Population of Substance Abusers Randomized, Placebo-Controlled Clinical Trial of Omega-3 as Supplemental Treatment in Schizophrenia Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study Omega-3 Fatty Acid Supplementation in Adolescents with Borderline Personality Disorder and Ultra-High Risk Criteria for Psychosis: A Post Hoc Subgroup Analysis of a Double—Blind, Randomized Controlled Trial A double-blind, randomized controlled clinical trial comparing eicosapentaenoic acid versus docosahexaenoic acid for depression. Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. The efficacy of omega-3 supplementation for major depression: a randomized controlled trial. Dietary Docosahexaenoic Acid Supplementation in Children With Autism A placebo-controlled cross-over trial of adjunctive EPA in OCD. Effects of Large Doses of Arachidonic Acid Added to Docosahexaenoic Acid on Social Impairment in Individuals With Autism Spectrum Disorders: A Double-Blind, Placebo-Controlled, Randomized Trial A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. The Effect of Flax Seed Cultivars with Differing Content of α-Linolenic Acid and Lignans on Responses to Mental Stress A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study. Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreases in anger and anxiety in substance abusers Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia Depletion of Omega-3 Fatty Acid Levels in Red Blood Cell Membranes of Depressive Patients A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Supplementation of n-3 Polyunsaturated Fatty Acids for Major Depressive Disorder: A Randomized, Double-Blind, 12-Week, Placebo-Controlled Trial in Korea Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder Double-Blind, Randomized, Placebo-Controlled Trials of Ethyl-Eicosapentanoate in the Treatment of Bipolar Depression and Rapid Cycling Bipolar Disorder The Effect of Omega-3 Fatty Acids on Psychophysiological Assessment for the Secondary Prevention of Posttraumatic Stress Disorder: An Open-Label Pilot Study Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms High dietary ratio of omega-6 to omega-3 polyunsaturated acids during pregnancy and prevalence of post-partum depression. Fish oil supplementation in the treatment of major depression: A randomised double-blind placebo-controlled trial Blinding was judged more difficult to achieve and maintain in nonpharmacologic than pharmacologic trials. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Omega-3 Fatty Acid Treatment, With or Without Cytidine, Fails to Show Therapeutic Properties in Bipolar Disorder: A Double-Blind, Randomized Add-on Clinical Trial Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial. Preliminary evidence that acute long-chain omega-3 supplementation reduces cardiovascular reactivity to mental stress: A randomized and placebo controlled trial Omega-3 Fatty Acids as a Treatment for Perinatal Depression: Randomized Double-Blind Placebo-Controlled Trial A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. Omega-3 supplements reduce self-reported physical aggression in healthy adults A Double-Blind Placebo-Controlled Trial of Omega-3 Fatty Acids as a Monotherapy for Adolescent Depression. Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders - Results from a double-blind, randomized and placebo-controlled clinical trial. A pilot randomized controlled trial of omega‐3 fatty acid supplementation for the treatment of anxiety in adolescents with anorexia nervosa A randomised controlled trial of vitamin D and omega-3 long chain polyunsaturated fatty acids in the treatment of irritability and hyperactivity among children with autism spectrum disorder Omega-3 polyunsaturated fatty acids and psychological intervention for workers with mild to moderate depression: A double-blind randomized controlled trial. The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial. Improving autism perinatal risk factors: A systematic review. Predictors of Hospitalization of Individuals With First-Episode Psychosis: Data From a 2-Year Follow-Up of the RAISE-ETP. Comparison of Therapeutic Effects of Omega-3 Fatty Acid Eicosapentaenoic Acid and Fluoxetine, Separately and in Combination, in Major Depressive Disorder A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. Oxidative stress reduction related to the efficacy of n-3 polyunsaturated fatty acids in first episode schizophrenia: Secondary outcome analysis of the OFFER randomized trial. Telomerase level increase is related to n-3 polyunsaturated fatty acid efficacy in first episode schizophrenia: Secondary outcome analysis of the OFFER randomized clinical trial Neuroprotective effects of ethyl-eicosapentaenoic acid in first episode psychosis: A longitudinal T2 relaxometry pilot study
OBJECTIVE Docosahexaenoic acid ( DHA ) might help prevent or attenuate posttraumatic stress disorder ( PTSD ) symptoms . We examined the efficacy and safety of DHA for preventing PTSD ( DSM-IV ) after severe accidental injury . METHOD From December 2008 to August 2013 , we conducted a r and omized , double-blind , placebo-controlled trial of 110 accident-injured patients consecutively admitted to an intensive care unit of the National Disaster Medical Center in Tokyo , Japan . All patients were taught about their psychological reactions to accidental injury for 20 minutes and were r and omly assigned to receive 1,470 mg/d of DHA plus 147 mg/d of eicosapentaenoic acid ( EPA ; n = 53 ) or placebo ( n = 57 ) for 12 weeks . The primary outcome was total score on the Clinician-Administered PTSD Scale ( CAPS ) at 3-month follow-up . Secondary outcomes included PTSD diagnosis ( full-blown or partial PTSD ) . Adherence to the interventions was assessed by erythrocyte fatty acid composition . RESULTS At 3 months , the CAPS total score revealed no differences between the 2 groups ( 10.78 in the DHA group vs 9.22 in the placebo group ; n = 100 ; P = .572 ) . We found that 11.1 % of the DHA group and 5.5 % of the placebo group developed PTSD . The erythrocyte level of DHA and EPA in the DHA group was significantly elevated compared to the placebo group ( P < .01 ) . CONCLUSIONS Docosahexaenoic acid supplementation was not superior to placebo for the secondary prevention of PTSD symptoms at 3 months after severe accidental injury . The efficacy of a different ratio of DHA and EPA and higher doses of omega-3 fatty acids as secondary prevention of PTSD remains to be determined . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00671099 OBJECTIVE Selective serotonin reuptake inhibitor ( SSRI ) medication does not appear to be effective in ill , malnourished anorexia nervosa ( AN ) patients . However , it may be effective in preventing relapse after weight restoration . The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects . METHOD Twenty-six subjects with AN participated in a trial of fluoxetine . In a double-blind , placebo-controlled manner , subjects received either nutritional supplements or a nutritional placebo . The nutritional supplement included tryptophan ( the precursor of serotonin ) , vitamins , minerals , and essential fatty acids believed to influence serotonin pathway function . RESULTS There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo . Moreover , there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms . DISCUSSION The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects This study investigated effects of PUFA and micronutrient supplementation on cognition in children with ADHD symptoms . In a r and omised controlled trial , 7 - 12-year-old children with symptoms 2 S.D. on Conners ' ADHD Index were given PUFA , PUFA+multivitamins/minerals ( MVM ) , or placebo for 15 weeks , and then all children were given PUFA+MVM for an additional 15 weeks . After 15 weeks there were improvements in a test of the ability to switch and control attention ( Creature Counting ) in the PUFA groups compared to placebo ( N=129 , p=0.002 ) . This improvement was also observed in the placebo group after taking PUFA from weeks 16 to 30 ( N=104 ) . There were no significant improvements in other cognitive measures , or with additional micronutrient supplementation . However , improvements in cognitive performance mediated previous parent-reported improvements in inattention , hyperactivity and impulsivity [ N. Sinn , J. Bryan , Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behaviour , J. Dev . Behav . Pediatr . 28 ( 2 ) ( 2007 ) 82 - 91 ] , suggestive of a common neurological mechanism for these symptoms BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients OBJECTIVE The purpose of this study was to compare the efficacy of ethyl-eicosapentaenoic acid ( E-EPA ) and placebo in the treatment of female subjects with borderline personality disorder . METHOD The authors conducted an 8-week , placebo-controlled , double-blind study of E-EPA in 30 female subjects meeting Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline personality disorder . RESULTS Twenty subjects were r and omly assigned to 1 g of E-EPA ; 10 subjects were given placebo . Ninety percent of those in both groups completed all 8 weeks of the trial . Analyses that used r and om-effects regression modeling and controlled for baseline severity showed E-EPA to be superior to placebo in diminishing aggression as well as the severity of depressive symptoms . CONCLUSIONS The results of this study suggest that E-EPA may be a safe and effective form of monotherapy for women with moderately severe borderline personality disorder Low dietary intakes of the n-3 long-chain PUFA ( LCPUFA ) EPA and DHA are thought to be associated with increased risk for a variety of adverse outcomes , including some psychiatric disorders . Evidence from observational and intervention studies for a role of n-3 LCPUFA in depression is mixed , with some support for a benefit of EPA and /or DHA in major depressive illness . The present study was a double-blind r and omised controlled trial that evaluated the effects of EPA+DHA supplementation ( 1.5 g/d ) on mood and cognitive function in mild to moderately depressed individuals . Of 218 participants who entered the trial , 190 completed the planned 12 weeks intervention . Compliance , confirmed by plasma fatty acid concentrations , was good , but there was no evidence of a difference between supplemented and placebo groups in the primary outcome - namely , the depression subscale of the Depression Anxiety and Stress Scales at 12 weeks . Mean depression score was 8.4 for the EPA+DHA group and 9.6 for the placebo group , with an adjusted difference of - 1.0 ( 95 % CI - 2.8 , 0.8 ; P = 0.27 ) . Other measures of mood , mental health and cognitive function , including Beck Depression Inventory score and attentional bias toward threat words , were similarly little affected by the intervention . In conclusion , substantially increasing  EPA+DHA  intake for 3 months was found not to have beneficial or harmful effects on mood in mild to moderate depression . Adding the present result to a meta- analysis of previous relevant r and omised controlled trial results confirmed an overall negligible benefit of n-3 LCPUFA supplementation for depressed mood Attention deficit/hyperactivity disorder ( ADHD ) is one of the most common child psychiatric disorders , and is often treated with stimulant medication . Nonpharmacological treatments include dietary supplementation with omega-3 fatty acids , although their effectiveness remains to be shown conclusively . In this study , we investigated the effects of dietary omega-3 fatty acid supplementation on ADHD symptoms and cognitive control in young boys with and without ADHD . A total of 40 boys with ADHD , aged 8–14 years , and 39 matched , typically developing controls participated in a 16-week double-blind r and omized placebo-controlled trial . Participants consumed 10 g of margarine daily , enriched with either 650 mg of eicosapentaenoic acid (EPA)/docosahexaenoic acid ( DHA ) each or placebo . Baseline and follow-up assessment s addressed ADHD symptoms , fMRI of cognitive control , urine homovanillic acid , and cheek cell phospholipid sampling . EPA/DHA supplementation improved parent-rated attention in both children with ADHD and typically developing children . Phospholipid DHA level at follow-up was higher for children receiving EPA/DHA supplements than placebo . There was no effect of EPA/DHA supplementation on cognitive control or on fMRI measures of brain activity . This study shows that dietary supplementation with omega-3 fatty acids  reduces symptoms of ADHD , both for individuals with ADHD and typically developing children . This effect does not appear to be mediated by cognitive control systems in the brain , as no effect of supplementation was found here . Nonetheless , this study offers support that omega-3 supplementation may be an effective augmentation for pharmacological treatments of ADHD ( NCT01554462 : The Effects of EPA/DHA Supplementation on Cognitive Control in Children with ADHD ; http:// clinical trials.gov/show/NCT01554462 ) Background and Objectives Some evidence of efficacy has been found for omega-3 fatty acids in patients with borderline personality disorder ( BPD ) . In a previous 12-week r and omized trial we assessed the efficacy of the combination of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) with valproic acid , in comparison with valproic acid monotherapy , in 43 BPD out patients . Combined therapy was superior to valproic acid monotherapy ( the control group ) in the treatment of some BPD symptoms : impulsive – behavioral dyscontrol , outbursts of anger , and self-harm . The present study is a 24-week follow-up aim ed at evaluating whether the differences in efficacy between the two subgroups were maintained after discontinuation of omega-3 fatty acids . Methods Thirty-four patients who completed the 12-week trial entered the follow-up study . Participants were evaluated at the beginning and at the end of the follow-up period using the rating scales that showed a significant difference between the groups after the 12-week trial with fatty acids supplementation : the Borderline Personality Disorder Severity Index ( BPDSI ) ( items ‘ impulsivity ’ and ‘ outbursts of anger ’ ) , Barratt Impulsiveness Scale – Version 11 ( BIS-11 ) , and Self Harm Inventory ( SHI ) . Statistical analysis was performed with analysis of variance ( ANOVA ) for repeated measures . Results At the end of the follow-up a significant difference within groups was maintained for all four variables examined , while a significant difference between groups was maintained for outbursts of anger . Concerning tolerability , no clinical ly significant adverse effects were registered during the follow-up period . Conclusions Combined therapy with omega-3 fatty acids showed long-lasting effects after discontinuation in terms of anger control . Trial registration The trial was registered in the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) and allocated the code : ACTRN12612001150831 This pilot study evaluated the effects of supplementation with PUFA on blood FA composition and behavior in children with Attention-Deficit/Hyperactivity Disorder (AD/HD)-like symptoms also reporting thirst and skin problems . Fifty children were r and omized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA , 80 mg EPA , 40 mg arachidonic acid ( AA ) , 96 mg GLA , and 24 mg α-tocopheryl acetate , or an olive oil placebo for 4 mon of doubleblind parallel treatment . Supplementation with the PUFA led to a substantial increase in the proportions of EPA , DHA , and α-tocopherol in the plasma phospholipids and red blood cell ( RBC ) total lipids , but an increase was noted in the plasma phospholipid proportions of 18∶3n-3 with olive oil as well . Significant improvements in multiple but outcomes ( as rated by parents ) were noted in both groups , but a clear benefit from PUFA supplementation for all behaviors characteristic of AD/HD was not observed . For most outcomes , improvement of the PUFA group was consistently nominally better than that of the olive oil group ; but the treatment difference was significantly , by secondary intent-to-treat analysis on only 2 out of 16 outcome measures : conduct problems rated by parents ( −42.7 vs. −9.9 % , n=47 , P=0.05 ) , and attention symptoms rated by teachers ( −14.8 vs. + 3.4 % , n=47 , P=0.03 ) . PUFA supplementation led to a greater number of participants showing improvement in oppositional defiant behavior from a clinical to a non clinical range compared with olive oil supplementation ( 8 out of 12 vs. 3 out of 11 , n=33 , P=0.02 ) . Also , significant correlations were observed when comparing the magnitude of change between increasing proportions of EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated Symptom Question naire ( ASQ ) for parents ( r=−0.38 , n=31 , P<0.05 ) , and for EPA and DHA in the RBC and the teachers ' Disruptive Behavior Disorders ( DBD ) Rating Scale for Attention ( r=−0.49 , n=24 , P<0.05 ) . Interestingly , significant correlations were observed between the magnitude of increase in α-tocopherol concentrations in the RBC and a decrease in scores for all four subscales of the teacher 's DBD ( Hyperactivity , r=−0.45 ; Attention , r=−0.60 ; Conduct , r=−0.41 ; Oppositional/Defiant Disorder , r=−0.54 ; n=24 , P<0.05 ) as well as the ASQ for teachers ( r=−0.51 , n=24 , P<0.05 ) . Thus , the results of this pilot study suggest the need for further research with both n−3 FA and vitamin E in children with behavioral disorders This pilot r and omized controlled trial ( RCT ) investigated benefits of omega-3 fatty acid supplementation and Individual-Family Psychoeducational Psychotherapy ( PEP ; a family-focused , cognitive-behavioral therapy ) for behavior problems among youth with depression . Participants aged 7–14 with DSM-IV-TR depressive disorders ( N = 72 ; 56.9 % male ) were r and omized to 1 of 4 treatment conditions : PEP + omega-3 , PEP monotherapy ( with pill placebo ) , omega-3 monotherapy , or placebo ( without active intervention ) . At screen , baseline , and 2 , 4 , 6 , 9 , and 12 weeks post-baseline , parents completed the SNAP-IV , which assesses attention-deficit/hyperactivity disorder symptoms , oppositional defiant disorder symptoms , and overall behavior problems . At screen , baseline ( r and omization ) , 6 and 12 weeks , parents completed the Eyberg Child Behavior Inventory ( ECBI ) , which includes Intensity and Problem scales for child behavior problems .  Youth who had a completed SNAP-IV or ECBI for at least two assessment s during treatment ( n = 48 and 38 , respectively ) were included in analyses of the respective outcome . Clinical Trials.gov.:NCT01341925 . Linear mixed effects models indicated a significant effect of combined PEP + omega-3  on SNAP-IV Total ( p = 0.022 , d = 0.80 ) and Hyperactivity/Impulsivity trajectories ( p = 0.008 , d = 0.80 ) , such that youth in the combined group saw greater behavioral improvement than those receiving only placebo . Similarly , youth in combined treatment had more favorable ECBI Intensity trajectories than youth who received no active treatment ( p = 0.012 , d = 1.07 ) . Results from this pilot RCT suggest that combined PEP + omega-3 is a promising treatment for co-occurring behavior symptoms in  youth with depression BACKGROUND Increasing evidence supports n-3 fatty acid ( FA ) supplementation for patients with psychiatric disorders , such as attention deficit hyperactivity disorder . However , the exact metabolic fate of dietary eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) on different glyceride carriers remains unclear . OBJECTIVE We investigated whether conjugation of EPA and DHA to phospholipid ( PL-n-3 ) or to triacylglycerol ( fish oil ; FO ) affects their incorporation in blood compartments and influences executive functioning . DESIGN Children aged 8 - 13 y with impaired visual sustained attention performance received placebo , 250 mg/d EPA + DHA esterified to PL-n-3 ( 300 mg/d phosphatidylserine ) , or FO for 3 mo in a r and omized double-blind manner . Main outcome measures included plasma and erythrocyte FA profile and continuous performance test results ( Test of Variables of Attention ; TOVA ) . RESULTS Sixty of the 83 children enrolled completed the interventions ( n = 18 - 21 per group ) . There was an enrichment of EPA ( 1.5 - 2.2-fold ) , docosapentaenoic acid ( DPA ; 1.2-fold ) , and DHA ( 1.3-fold ) in the PL fraction in the plasma of FO- and PL-n-3-fed children . In erythrocytes , only PL-n-3 result ed in a significant reduction ( approximately 30 % ) of very-long-chain saturated FAs ( C20 - 24 ) and in an increase ( 1.2- and 2.2-fold , respectively ) in linoleic acid and DPA . Total TOVA scores increased in the PL-n-3 ( mean + /- SD : 3.35 + /- 1.86 ) and FO ( 1.72 + /- 1.67 ) groups but not in the placebo group ( -0.42 + /- 2.51 ) ( PL-n-3 > FO > placebo ; P < 0.001 ) . A significant correlation between the alterations in FAs and increased TOVA scores mainly occurred in the PL-n-3 group . CONCLUSION Consumption of EPA+DHA esterified to different carriers had different effects on the incorporation of these FAs in blood fractions and on the visual sustained attention performance in children . This trial was registered at clinical trials.gov as NCT00382616 OBJECTIVE Preliminary evidence suggests that omega-3 fatty acids may reduce  hyperactivity in children with autism spectrum disorder ( ASD ) . We sought to examine the feasibility of a novel , Internet-based clinical trial design to evaluate the efficacy of this supplement . METHOD E-mail invitations were sent to parents of children aged 5 to 8 years enrolled in the Interactive Autism Network .  All study procedures , including screening , informed consent , and collection of outcome measures took place over the Internet . The primary outcome measures were parent- and teacher-rated changes in hyperactivity on the Aberrant Behavior Checklist ( ABC-H ) . RESULTS During the 6-week recruitment period , 57 children from 28 states satisfied all eligibility criteria and were r and omly assigned to 1.3 grams of  omega-3 fatty acids or an identical placebo daily for 6 weeks . Outcome assessment s were obtained from all 57 participants and 57 teachers , and the study was completed in 3 months . Children in the omega-3 fatty acid group had a greater reduction in hyperactivity ( -5.3 points ) compared to the placebo group ( -2.6 points ) , but the difference was not statistically significant ( 1.9-point greater improvement in the omega-3 group , 95 % CI = -2.2 to 5.2 ) . Adverse events were rare and not associated with omega-3 fatty acids . Participant feedback was positive . CONCLUSION Internet-based , r and omized controlled trials of therapies in children with ASD are feasible and may lead to marked reductions in the time and cost of completing trials . A larger sample size is required to definitively determine the efficacy of omega-3 fatty acids . Clinical trial registration information-Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder ; http:// clinical trials.gov ; NCT01694667 BACKGROUND While antipsychotics are effective in the maintenance treatment of schizophrenia they have safety and tolerability risks . We investigated whether a combination of omega-3 polyunsaturated fatty acids ( ω-3 PUFAs ) and a metabolic antioxidant , alpha-lipoic acid ( α-LA ) , is effective in preventing relapse after antipsychotic discontinuation in subjects who were successfully treated for 2 - 3 years after a first-episode of schizophrenia , schizo-affective or schizophreniform disorder . METHODS In this r and omized , double-blind , placebo controlled study antipsychotic treatment was tapered and discontinued and participants received either ω-3 PUFAs ( eicosapentaenoic acid 2g/day and docosahexaenoic acid 1g/day)+α-LA 300 mg/day or placebo . Subjects were followed up for two years , or until relapse . RESULTS Recruitment was terminated prematurely due to the high relapse rates in both treatment groups as well as the severity of some of the relapse episodes . Of the 33 participants , 19/21(90 % ) r and omized to ω-3 PUFAs+α-LA  relapsed and one ( 5 % ) completed two years without relapse ( p=0.6 ) ; and 9/12 ( 75 % ) r and omized to placebo relapsed and none completed two years without relapse . Mean times to relapse were 39.8 ± 25.4 and 38.3 ± 26.6 weeks for the ω-3 PUFAs+α-LA and placebo groups , respectively ( p=0.9 ) . There were no significant differences between the groups in relapse symptom severity . CONCLUSIONS We found no evidence that ω-3 PUFAs+α-LA could be a suitable alternative to maintenance antipsychotic treatment in relapse prevention , in this small study . Antipsychotic discontinuation after a single episode of schizophrenia carries a very high risk of relapse , and treatment guidelines endorsing this practice should be revised Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids ( PUFAs ) , including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents ( red blood cell membrane , plasma , etc . ) and dietary intake . However , more evidence is needed to support its relation . In this study , we conducted an 8-week , double-blind , placebo-controlled trial , comparing omega-3 PUFAs ( 6.6 g/day ) [ corrected ] with placebo , on the top of the usual treatment , in 28 patients with major depressive disorder . Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group ( P < 0.001 ) . From the preliminary findings in this study , omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder OBJECTIVE Worldwide , conventional antipsychotic medication continues to be used extensively , and tardive dyskinesia ( TD ) remains a serious complication . The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD . METHOD This was a 12-week , double-blinded , r and omized study of ethyl-EPA 2g/day versus placebo as supplemental medication , in patients with schizophrenia or schizoaffective disorder , with established TD . RESULTS Eighty-four subjects were r and omized , of whom 77 were included in the analysis . Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores , but there were no significant between-group differences ( p=0.4 ) . Response rates ( > or=30 % improvement in TD symptoms ) also did not differ significantly between EPA-treated subjects ( 45 % ) and placebo-treated subjects ( 32 % ) ( p=0.6 ) . However , a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD . The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially , although this was not sustained beyond 6 weeks . CONCLUSIONS This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure . However , a modest and transient benefit is suggested in patients with more recent onset of TD . The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low , the study being underpowered , TD being too chronic in the majority of cases , differences in dietary fatty acid intake , or that EPA lacks an anti-dyskinetic action Controversy exists as to whether eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) or both are responsible for the efficacy of n-3 polyunsaturated fatty acids in depression . We conducted a single-center , r and omized , double-blind , placebo-controlled , multi-arm , parallel-group trial , comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression . Eighty-one mild-to-moderately depressed out patients were r and omly assigned to receive either 1g/d of EPA or DHA or placebo ( coconut oil ) for 12 weeks . The primary outcome measure was the 17-item Hamilton Depression Rating Scale ( HDRS ) final score in the modified intention-to-treat population , which comprised of all r and omized patients with at least 1 post-r and omization observation ( n=62 ; 61.3 % female ; mean age 35.1 ± 1.2 years ) . Allocated treatments were well tolerated . Although there was no significant difference between groups at baseline , patients in the EPA group showed a significantly lower mean HDRS score at study endpoint compared with those in the DHA ( p<0.001 ) or placebo ( p=0.002 ) groups . Furthermore , response to treatment ( defined as a ≥ 50 % decrease from the baseline HDRS score ) was only observed in 6 patients receiving EPA , while no one in any of DHA or placebo groups responded to treatment . Overall , these data suggest greater efficacy of EPA compared to DHA or placebo as an adjunctive treatment in mild-to-moderate depression . However , further , r and omized controlled trials are needed to support these findings Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia . We examined the clinical effect of adding an omega-3 fatty acid and /or vitamins E+C to antipsychotics . It was hypothesized that lower baseline levels of polyunsaturated fatty acids ( PUFAs ) would predict more benefit from the add-on treatment . The trial had a multicenter , r and omized , double-blind , placebo-controlled 2 × 2 factorial design . Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway . They received active or placebo ethyl-eicosapentaenoate ( EPA ) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 ( vitamins ) for 16 weeks . The main outcome measures were Positive and Negative Syndrome Scale ( PANSS ) total and subscales scores , analyzed by linear mixed models . Ninety-nine patients were included . At baseline , erythrocyte PUFA were measured in 97 subjects . Given separately , EPA and vitamins  increased drop-out rates , whereas when combined they did not differ from placebo . In low PUFA patients , EPA alone impaired the course of total PANSS ( Cohen ’s d=0.29 ; P=0.03 ) and psychotic symptoms ( d=0.40 ; P=0.003 ) , especially persecutory delusions ( d=0.48 ; P=0.0004 ) . Vitamins alone impaired the course of psychotic symptoms ( d= 0.37 ; P=0.005 ) , especially persecutory delusions ( d=0.47 ; P=0.0005 ) . Adding vitamins to EPA neutralized the detrimental effect on psychosis ( interaction d=0.31 ; P=0.02 ) . In high PUFA patients , there were no significant effects of trial drugs on PANSS scales . In conclusion , given separately during an acute episode , EPA and vitamins E+C  induce psychotic symptoms in patients with low levels of PUFA . Combined , these agents seem safe Background Depression is one of the most frequently missed diagnoses in elderly people , with obvious negative effects on quality of life . Various studies have shown that long chain omega-3 polyunsaturated fatty acids ( n-3 PUFA ) may be useful in its management . Our objective was to evaluate whether a supplement containing n-3 PUFA improves depressive symptoms in depressed elderly patients , and whether the blood fatty acid pattern is correlated with these changes . Methods The severity of depressive symptoms according to the Geriatric Depression Scale ( GDS ) , blood fatty acid composition and erythrocyte phospholipids were analyzed in 46 depressed females aged 66 - 95y , diagnosed with depression according to DSMIV , within the context of a r and omized , double-blind , placebo-controlled trial . 22 depressed females were included in the intervention group ( 2.5 g/day of n-3 PUFA for 8 weeks ) , and 24 in the  placebo  group . We also measured immunological parameters ( CD2 , CD3 , CD4 , CD8 , CD16 , CD19 and cytokines ( IL-5 , IL-15 ) . Results The mean GDS score and AA/EPA ratio , in whole blood and RBC membrane phospholipids , were significantly lower after 2 months supplementation with n-3 PUFA . A significant correlation between the amelioration of GDS and the AA/EPA ratio with some immunological parameters , such as CD2 , CD19 , CD4 , CD16 and the ratio CD4/CD8 , was also found . Nevertheless , omega-3 supplementation did not significantly improve the studied immunological functions . Conclusions n-3 PUFA supplementation ameliorates symptoms in elderly depression . The n-3 PUFA status may be monitored by means of the determination of whole blood AA/EPA ratio OBJECTIVES This clinical trial evaluated whether supplementation with flax oil , containing the omega-3 fatty acid alpha-linolenic acid ( alpha-LNA ) , safely reduced symptom severity in youth with bipolar disorder . METHODS Children and adolescents aged 6 - 17 years with symptomatic bipolar I or bipolar II disorder ( n = 51 ) , manic , hypomanic , mixed , or depressed , were r and omized to either flax oil capsules containing 550 mg alpha-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy . Doses were titrated to 12 capsules per day as tolerated over 16 weeks . Primary outcomes included changes in the Young Mania Rating Scale , Child Depression Rating Scale-Revised , and Clinical Global Impressions-Bipolar ratings using Kaplan-Meier survival analyses . RESULTS There were no significant differences in primary outcome measures when compared by treatment assignment . However , clinician-rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions : % alpha-LNA ( r = -0.45 , p < 0.007 ) , % eicosapentaenoic acid ( EPA ) ( r = -0.47 , p < 0.005 ) ; and positively correlated with final arachidonic acid ( AA ) ( r = 0.36 , p < 0.05 ) and docosapentaenoic acid ( DPA ) n-6 ( r = 0.48 , p < 0.004 ) . The mean duration of treatment for alpha-LNA was 11.8 weeks versus 8 weeks for placebo ; however , the longer treatment duration for alpha-LNA was not significant after controlling for baseline variables . Subjects discontinued the study for continued depressive symptoms . CONCLUSIONS Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population . Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and /or decreased AA and DPA n-6 levels , individual variations in conversion of alpha-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice . Additionally , future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions , as opposed to group r and omization alone OBJECTIVE The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid ( E-EPA ) as add-on treatment in chronic , severe schizophrenia . METHOD A r and omized , parallel-group , double-blind , placebo-controlled , fixed-dose , add-on study was conducted over 12 weeks . Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo , in addition to their existing treatment . RESULTS At 12 weeks , the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group . CONCLUSIONS EPA may be an effective and well-tolerated add-on treatment in schizophrenia OBJECTIVE To determine whether supplementation with the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic ( EPA ) and docosahexaenoic acid ( DHA ) affects behavioral symptoms and cognitive impairments in children 6 - 12 years of age diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) . STUDY DESIGN The r and omized , double-blind placebo-controlled 16 weeks trial was conducted with 95 children diagnosed with ADHD according to DSM-IV criteria . Behavior was assessed by parents , teachers and investigators using st and ardized rating scales and question naires . Further outcome variables were working memory , speed of information processing and various measures of attention . For a subgroup of 81 participants , erythrocyte membrane fatty acid composition was analyzed before and after the intervention . RESULTS Supplementation with the omega-3 fatty acid mix increased EPA and DHA concentrations in erythrocyte membranes and improved working memory function , but had no effect on other cognitive measures and parent- and teacher-rated behavior in the study population . Improved working memory correlated significantly with increased EPA , DHA and decreased AA ( arachidonic acid ) OBJECTIVES To investigate whether docosahexaenoic acid ( DHA ) supplementation was able to ameliorate attention-deficit/hyperactivity disorder(AD/HD ) symptoms in AD/HD children . DESIGN AND SUBJECTS A placebo-controlled double-blind study with 40 AD/HD ( including eight AD/HD-suspected ) children of 6 - 12 y of age who were mostly without medication . Subjects of a DHA group ( n=20 ) took active foods containing fish oil ( fermented soybean milk , bread rolls and steamed bread ; 3.6 g DHA/week from these foods ) for 2 months , whereas those of a control group ( n=20 ) took indistinguishable control foods without fish oil . The following items were measured at the start and end of the study : ( 1 ) attention deficit , hyperactivity and impulsivity ( AD/HD-related symptoms according to DSM-IV criteria ) ; ( 2 ) aggression assessed by both parents and teachers ; ( 3 ) visual perception ( finding symbols out of a table ) ; ( 4 ) visual and auditory short-term memory ; ( 5 ) development of visual-motor integration ; ( 6 ) continuous performance ; ( 7 ) impatience . RESULTS Changes in tests 1 , 2 , 3 , 5 and 7 over time did not significantly differ between the two groups . However , visual short-term memory and errors of commission ( continuous performance ) significantly improved in the control group compared with the changes over time in the DHA group ( P=0.02 and 0.001 , respectively ) . Recalculation without AD/HD-suspected subjects ( n=4 each group ) showed similar P-values with regard to both measures . CONCLUSION DHA supplementation did not improve AD/HD-related symptoms . Treatment of ADHD with fatty acids deserves further investigation , but careful attention should be paid as to which fatty acid(s ) is used Long-chain omega-3 polyunsaturated fatty acids ( PUFAs ) are essential for neural development and function . As key components of brain tissue , omega-3 PUFAs play critical roles in brain development and function , and a lack of these fatty acids has been implicated in a number of mental health conditions over the lifespan , including schizophrenia . We have previously shown that a 12-week intervention with omega-3 PUFAs reduced the risk of progression to psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared with placebo . We have now completed a longer-term follow-up of this r and omized , double-blind , placebo-controlled trial , at a median of 6.7 years . Here we show that brief intervention with omega-3 PUFAs reduced both the risk of progression to psychotic disorder and psychiatric morbidity in general in this study . The majority of the individuals from the omega-3 group did not show severe functional impairment and no longer experienced attenuated psychotic symptoms at follow-up The current study examined the psychological effects of acute and low-dose long-chain omega-3 polyunsaturated fatty acids ( LCPUFAs ) supplementation on young adults with depressive symptoms . Participants ( N=23 , M age (SD)=20.2 ( 1.25 ) , 78 % female ) , with a Beck Depression Inventory ( BDI ) score of greater than 10 , were r and omly assigned to a placebo ( corn oil ) or LCPUFAs group ( 1.4 g of eicosapentaenoic and docosahexaeonic acids ) and were instructed to consume the assigned capsules daily for 21-days . BDI was completed prior to supplementation and at day 21 . Group differences in depression status on day 21 were analyzed using chi-square tests . After 21-days of supplementation , there was a significant difference in depression status between groups . 67 % of the LCPUFAs no longer met criteria for being depressed , while only 20 % in the placebo group were no longer depressed . A mixed ANOVA revealed a significant group x time interaction for BDI scores . Post-hoc analyses revealed the LCPFUAs group had a significant reduction in BDI scores over time , while the placebo group 's scores did not significantly change . These findings suggest that LCPUFAs may alter depression and depressive symptomology in young adults in a relatively short amount of time BACKGROUND Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate , 2 effective treatments for bipolar disorder . The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder . METHODS A 4-month , double-blind , placebo-controlled study , comparing omega3 fatty acids ( 9.6 g/d ) vs placebo ( olive oil ) , in addition to usual treatment , in 30 patients with bipolar disorder . RESULTS A Kaplan-Meier survival analysis of the cohort found that the  omega3 fatty acid  patient group had a significantly longer period of remission than the placebo group ( P = .002 ; Mantel-Cox ) . In addition , for nearly every other outcome measure , the omega3 fatty acid group performed better than the placebo group . CONCLUSION Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder Objective Recent observations showed that long chain omega 3 polyunsaturated fatty acids ( n-3 LCPUFA ) could represent a potential treatment for elderly depression . To determine if a n-3 LCPUFA containing supplement improves depressive symptoms , changes phospholipids acids profile and ameliorates Health related quality of life ( HRQoL ) in depressed elderly patients . Design Two-months , r and omized , double-blind , placebo-controlled trial . Setting Nursing home in Pavia , Italy . SubjectsForty-six depressed females , aged 66–95 years . Intervention22 depressed females were included in the  intervention group ( n-3 group , that received 2.5 g/day of n-3 LCPUFA , with 1.67 grams of EPA and 0.83 grams of DHA ) , and 24 patients in the placebo group . The primary endpoint was the improvement of depressive symptoms as evaluated by Geriatric Depression Scale ( GDS ) . Secondary endpoints were the evaluation of modifications of erythrocyte membrane phospholipids fatty acid profile and of of HRQoL , by using the Short-Form 36-Item Health Survey ( SF-36 ) . All parameters were assessed before and after the treatment period of 8 weeks . Results The mean GDS at 2 months was significantly lowered only for the n-3 group . SF-36 physical and mental components were significantly increased in the intervention group . Compliance was good , as confirmed by erythrocyte membrane phospholipid FA concentrations , with significant increase of EPA and DHA in the intervention group . Conclusion The supplementation of n-3 LCPUFA in elderly female patients reduces the occurrence of depressive symptoms , improves phospholipids fatty acids profile and healthrelated quality of life Anorexia nervosa ( AN ) carries the highest risk of morbidity and mortality amongst psychiatric disorders . The efficacy of current treatment approaches is limited . Despite the fat-phobic nature of the disease , poly-unsaturated fatty acids ( PUFAs ) have not received much research attention . Patients who consume western diet , which is rich in n-6 PUFAs and trans-fatty acids , are likely to develop severe n-3 PUFA deficiency during self-induced starvation . Re-feeding programmes do not take into consideration n-3 EFA intake , possibly leading to further n-3 PUFA deficiency during weight restoration , and this might contribute to the maintenance of the disorder . To test this hypothesis , we carried out a systematic case series of E-EPA supplementation in the treatment of AN . Seven young patients received 1g/day E-EPA in addition to st and ard treatment , and were followed up for 3 months . Three of them recovered and four improved . R and omised controlled trials are warranted to examine the effectiveness of E-EPA  in AN further OBJECTIVE To investigate if ethyl-eicosapentaenoic acid ( E-EPA ) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis ( FEP ) . METHOD We performed a 12-week , r and omized , double-blind , placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients . Sixty-nine patients were eligible for analysis ; a post hoc analysis was computed for a subgroup of nonaffective FEP patients ( N = 53 ) . The first participant was included in November 2000 and the last participant completed the trial in August 2003 . Primary outcome measures were symptom change scores and time to first response , while tolerability measures and cumulative antipsychotic dose were secondary outcome measures . RESULTS Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores . Cox regression analysis revealed a significant treatment by diagnosis interaction ( p = .024 ) for time to first response favoring E-EPA in nonaffective psychosis . Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 ( 42.9 % [ 15/35 ] vs. 17.6 % [ 6/34 ] for all participants , p = .036 ; 54.2 % [ 13/24 ] vs. 17.2 % [ 5/29 ] for the nonaffective psychosis subset , p = .008 ) ; however , the difference at week 12 was no longer significant . Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20 % less antipsychotic medication between weeks 4 through 6 ( p = .03 ) , had less extrapyramidal side effects in the initial 9 weeks ( p < .05 for all participants and for all timepoints ) , and reported less constipation ( p = .011 ) and fewer sexual side effects ( p = .016 ) than those treated with antipsychotic medication alone . CONCLUSION The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications . However , it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis , possibly due to a ceiling effect , since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone . Further controlled trials in nonaffective early psychosis seem warranted . TRIAL REGISTRATION Australian Clinical Trials Registry identifier 12605000267651 ( http://actr.org.au ) Children ( 6 - 12 years ) with attention-deficit hyperactivity disorder ( ADHD ) being treated with methylpheni date and st and ard behavior therapy for more than 6 months , whose parents reported no improvement in behavior and academic learning , were r and omly assigned to receive supplementation with a combined ω3 and ω6 preparation or a placebo . Outcome was measured at 3 and 6 months after treatment using a self- assessment checklist completed by the parents . Statistically significant improvement was found in the treatment group compared with the placebo group ( P < .01 ) in the following measures : restlessness , aggressiveness , completing work , and academic performance . Statistically significant improvement was not found at 3 months of treatment between groups but was evident at 6 months of treatment ( P < .05 ) with inattention , impulsiveness , and cooperation with parents and teachers . Distractibility failed to show improvement . Effect sizes ranged from 0.3 to 1.1 at 3 months and 0.2 to 1.4 at 6 months for individual symptom variables Objective : In elderly individuals , depression is one of the most frequently missed diagnoses with negative effects on quality of life . The authors investigated whether a supplement containing long-chain omega-3 polyunsaturated fatty acids ( n-3 LCPUFA ) improves depressive symptoms and health-related quality of life ( HRQoL ) in depressed elderly patients . Design : Eight-week , r and omized , double-blind , placebo-controlled trial . Setting : Nursing home in Pavia , Italy . Participants : Forty-six depressed women , aged 66–95 years . Intervention : Twenty-two depressed women were included in the intervention group ( n-3 group , which received 2.5 g/d of n-3 LCPUFA , with 1.67 g of eicosapentaenoic acid [ EPA ] and 0.83 g of docosahesaenoic acid [ DHA ] ) , and 24 patients were included in the placebo group . The primary endpoint was the improvement of depressive symptoms , as evaluated by the Geriatric Depression Scale ( GDS ) . Secondary endpoints were the evaluation of HRQoL , by using the Short-Form 36-Item Health Survey ( SF-36 ) , and modifications of erythrocyte membrane phospholipids fatty acid profile . All variables were assessed before and after the treatment period of 8 weeks . Results : The mean GDS at 8 weeks was significantly lower compared with the n-3 group . The SF-36 physical and mental components were significantly increased in the intervention group . Compliance was good , as confirmed by erythrocyte membrane phospholipid FA concentrations , with a significant increase of EPA and DHA in the intervention group . Conclusion : Supplementation with n-3 LCPUFA is efficacious in the amelioration of depressive symptoms and quality of life in the treatment of depressed elderly female patients Beneficial effects of omega-3 fatty acids have been reported for several psychiatric disorders , particularly for depression . Association studies show a relationship between omega-3 intake and depression risk . Meta-analyses of clinical trials have shown a moderate effect of supplementation on depressive symptoms , but not on normal mood states . Few studies have investigated effects on cognition . The purpose of this study was to examine effects of omega-3 supplements on cognition and mood of recovered depressed individuals . Seventy-one participants were r and omized to receive either omega-3 or placebo for four weeks in a r and omized double-blind design . Results showed small effects of omega-3 supplementation on aspects of emotional decision-making and on self-reported states of depression and tension . Some of the effects were confounded by learning effects . No significant effects were observed on memory , attention , cognitive reactivity and depressive symptoms . While inconclusive , the present findings may indicate that omega-3 supplementation has selective effects on emotional cognition and mood in recovered depressed participants Background Autism spectrum disorder ( ASD ) is a neurodevelopmental disorder affecting more than 1 % of children . It is characterized by social communication deficits and repetitive behaviors/restricted interests . In the absence of any medications known to improve core symptom domains , parents often use complementary alternative treatments , including omega-3 fatty acid supplements . Methods We conducted a 6-month , r and omized , placebo controlled trial of omega-3 fatty acid supplements ( 1.5 g ) vs placebo in children 2 to 5 years of age with ASD . Primary outcome measures included the autism composite score of the Pervasive Developmental Disorders Behavioral Inventory ( PDDBI ) and the externalizing problems score of the Behavior Assessment System for Children ( BASC-2 ) . Secondary outcome measures included clinical global improvement ( Clinical Global Impression-Improvement ( CGI-I ) ) , adaptive function ( Vinel and Adaptive Behavior Scale ( VABS-II ) ) , and language gains ( Preschool Language Scale ( PLS-4 ) ) , as well as safety . Exploratory analysis investigated potential correlations between changes in cytokine profiles and treatment response . Results Thirty-eight participants were r and omized in a 1:1 fashion . There was no significant difference between groups on the 0- to 24-week change in PDDBI autism composite scores ( p = 0.5 ) . There was a significant group by week interaction on the BASC-2 externalizing problem score , with participants r and omized to the treatment group demonstrating worsening scores ( p = 0.02 ) . There was no statistically significant week by group effect on either adaptive function ( p = 0.09 ) or language ( p = 0.6 ) . Omega-3s were relatively well tolerated . Changes in cytokines during the study did not significantly correlate with treatment response . Conclusions This study does not support high dose supplementation of omega-3 fatty acids in young children with ASD.Trial registration Clinical trials.gov NCT01248728 . Registered 22 November 2010 OBJECTIVE This study was design ed to explore the relationship in between the daily consumption of fish oil ( 360 mg DHA+540 mg EPA ) , and reduction of symptoms and violent behavior among patients with schizophrenia . METHOD Fifty in patients meeting ICD-10 criteria for schizophrenia and scoring more than four of Modified Overt Aggression Scale ( MOAS ) with antipsychotics treatment were r and omly assigned to receive either fish oil ( N=28 ) or a placebo ( N=22 ) in a twelve week , double-blind supplementation trial . Assessment s were performed at baseline and at weeks 4 , 8 and 12 . RESULTS The PANSS and CGI scores decreased at the week of 4 , 8 and 12 , but no differences were found between the two groups . MOAS scores declined significantly at weeks 4 , 8 and 12 . At week 12 , MOAS scores of the fish oil group declined significantly than the placebo group ( t=-2.40 , P<0.05 ) . CONCLUSIONS violent schizophrenia patients treated with fish oil ( 360 mg DHA+540 mg EPA ) demonstrated a decrease in violence , but improvement in positive and negative symptoms was no greater than patients treated with the placebo after twelve weeks OBJECTIVE To study the efficacy and safety of phosphatidylserine ( PS ) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone ( PS-Omega3 ) in reducing attention-deficit/ hyperactivity disorder ( ADHD ) symptoms in children . METHOD A 15-week , double-blind , placebo-controlled phase followed by an open-label extension of additional 15 weeks . Two hundred ADHD children were r and omized to receive either PS-Omega3 or placebo , out of them , 150 children continued into the extension .  Efficacy was assessed using Conners ' parent and teacher rating scales ( CRS-P , T ) , Strengths and Difficulties Question naire ( SDQ ) , and Child Health Question naire ( CHQ ) . Safety evaluation included adverse events monitoring . RESULTS The key finding of the double-blind phase was the significant reduction in the Global : Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional ( PE ) subscale of the CHQ , both in the PS-Omega3 group . Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior , as well as mood and behavior-dysregulation , revealed a significant reduction in the ADHD-Index and hyperactive components . Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3 . Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T , as compare to baseline scores . The treatment was well tolerated . CONCLUSIONS The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children . Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive , emotionally and behaviorally-dysregulated ADHD children ( 1 ) The authors tested the prediction that relative deficiencies in highly unsaturated fatty acids ( HUFAs ) may underlie some of the behavioral and learning problems associated with attention-deficit/hyperactivity disorder ( ADHD ) by study ing the effects of HUFA supplementation on ADHD-related symptoms in children with specific learning difficulties ( mainly dyslexia ) who also showed ADHD features . ( 2 ) Forty-one children aged 8 - 12 years with both specific learning difficulties and above-average ADHD ratings were r and omly allocated to HUFA supplementation or placebo for 12 weeks . ( 3 ) At both baseline and follow-up , a range of behavioral and learning problems associated with ADHD was assessed using st and ardized parent rating scales . ( 4 ) At baseline , the groups did not differ , but after 12 weeks mean scores for cognitive problems and general behavior problems were significantly lower for the group treated with HUFA than for the placebo group ; there were significant improvements from baseline on 7 out of 14 scales for active treatment , compared with none for placebo . Group differences in change scores all favored HUFA , reaching conventional significance levels for 3 out of 14 scales . ( 5 ) HUFA supplementation appears to reduce ADHD-related symptoms in children with specific learning difficulties . Given the safety and tolerability of this simple treatment , results from this pilot study strongly support the case for further investigations Objective The objective of this study was to explore the efficacy of combination therapy with citalopram plus omega-3 fatty acids versus citalopram plus placebo ( olive oil ) in the initial treatment of individuals with major depressive disorder ( MDD ) . We hypothesized that combination therapy would lead not only to greater efficacy but also to a more rapid onset of therapeutic response . Methods Forty-two subjects participated in this 9-week r and omized , masked , placebo-controlled study of combination therapy ( two 1 g capsules containing a blend of 900 mg of eicosapentaenoic acid , 200 mg of and docosahexaenoic acid , and 100 mg of other omega-3 fatty acids twice daily plus citalopram ) versus monotherapy ( two 1 g capsules of olive oil per day plus citalopram ) treatment of MDD . Results The combination therapy demonstrated significantly greater improvement in Hamilton Depression Rating scale scores over time ( F = 7.32 ; df 1,177 ; P = 0.008 ) beginning at week 4 ( t = −2.48 ; df 177 ; P = 0.014 ) . Conclusions Combination therapy was more effective than monotherapy in decreasing signs and symptoms of MDD during the 8 weeks of active treatment ; however , combination therapy did not seem to enhance the speed of the initial antidepressant response . These findings suggest that there may be an advantage to combining omega-3 fatty acids with a selective serotonin uptake inhibitor in the initial treatment of individuals with MDD . A larger definitive study is warranted We conducted a pilot r and omized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids ( 1.3 g/day ) for the treatment of hyperactivity in 27 children ages 3–8 with autism spectrum disorder ( ASD ) . After 12 weeks , hyperactivity , as measured by the Aberrant Behavior Checklist , improved 2.7 ( ±4.8 ) points in the omega-3 group compared to 0.3 ( ±7.2 ) points in the placebo group ( p = 0.40 ; effect size = 0.38 ) . Correlations were found between decreases in five fatty acid levels and decreases in hyperactivity , and the treatment was well tolerated . Although this pilot study did not find a statistically significant benefit from omega-3 fatty acids , the small sample size does not rule out small to moderate beneficial effects OBJECTIVE Major depressive disorder in children may be more common than previously thought , and its therapeutics are unclear . Because of success in a previous study on omega-3 fatty acids in adult major depressive disorder , the authors planned a pilot study of omega-3 fatty acids in childhood major depression . METHOD Children who entered the study were between the ages of 6 and 12 . Ratings were performed at baseline and at 2 , 4 , 8 , 12 , and 16 weeks using Children 's Depression Rating Scale ( CDRS ) , Children 's Depression Inventory ( CDI ) , and Clinical Global Impression ( CGI ) .  Children were r and omized to  omega-3 fatty acids or placebo as pharmacologic monotherapy . Twenty-eight patients were r and omized , and 20 completed at least 1 month 's ratings . RESULTS Analysis of variance showed highly significant effects of omega-3 on symptoms using the CDRS , CDI , and CGI . CONCLUSIONS Omega-3 fatty acids may have therapeutic benefits in childhood depression Background On March 11 , 2011 , a magnitude 9.0 earthquake , the most powerful ever recorded in Japan , and a massive tsunami struck off the coast of the Sanriku region . A Disaster Medical Assistance Team , a mobile medical team with specialized training that is deployed during the acute phase of a disaster , was dispatched to areas with large-scale destruction and multiple injured and sick casualties . Previous studies have reported critical incident stress ( i.e. posttraumatic stress disorder symptoms and depressive symptoms ) among rescue workers as well as the need for screening and prevention for posttraumatic stress disorder . So far we have shown in an open trial that posttraumatic stress disorder symptoms in critically injured patients can be reduced by taking omega-3 fatty acids intended to stimulate hippocampal neurogenesis . Method / Design This study is design ed to determine the effectiveness of attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among Disaster Medical Assistance Team members after the Great East Japan Earthquake , and is named the APOP r and omized controlled trial which is currently ongoing . First , we will provide psycho-education on posttraumatic distress , which is common in responders to the Disaster Medical Assistance Team members deployed to the disaster area . Second , observational research will be conducted to evaluate critical incident stress following the completion of medical activities . Third , team members who provide consent to participate in the intervention research will be r and omly divided into a group given an omega-3 fatty acid supplement and a group not given the supplements . Outcome will be evaluated at 12 weeks after the supplements are shipped to the team members . Discussion Measures that address critical incident stress in disaster responders are important , but there is no substantial evidence that links such measures with prevention of posttraumatic stress disorder . Thus , any confirmation through this study that the intake of omega-3 fatty acid supplements serves as a simple preventative measure for critical incident stress will be of great significance .Trial registration UMIN Clinical Trials Registry , This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 ( n-3 ) fatty acids in subjects with major depressive disorder ( MDD ) . One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( DSM-IV ) MDD , a baseline 17-item Hamilton Depression Rating Scale ( HAM-D-17 ) score ⩾15 and baseline biomarker data ( interleukin (IL)-1ra , IL-6 , high-sensitivity C-reactive protein ( hs-CRP ) , leptin and adiponectin ) were r and omized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day−1 , docosahexaenoic acid (DHA)-enriched n-3 900 mg day−1 or placebo . Outcomes were determined using mixed model repeated measures analysis for ‘ high ’ and ‘ low ’ inflammation groups based on individual and combined biomarkers . Results are presented in terms of st and ardized treatment effect size ( ES ) for change in HAM-D-17 from baseline to treatment week 8 . Although overall treatment group differences were negligible ( ES=−0.13 to + 0.04 ) , subjects with any ‘ high ’ inflammation improved more on EPA than placebo ( ES=−0.39 ) or DHA ( ES=−0.60 ) and less on DHA than placebo ( ES=+0.21 ) ; furthermore , EPA-placebo separation increased with increasing numbers of markers of high inflammation . Subjects r and omized to EPA with ‘ high ’ IL-1ra or hs-CRP or low adiponectin ( ‘ high ’ inflammation ) had medium ES decreases in HAM-D-17 scores vs subjects ‘ low ’ on these biomarkers . Subjects with ‘ high ’ hs-CRP , IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers ( medium to large ES differences ) . Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort . Studies are needed to replicate and extend this proof-of-concept work There is mounting evidence that low levels of n-3 polyunsaturated fatty acids ( PUFAs ) play a role in the pathophysiology of a number of psychiatric disorders . Pre clinical studies have shown that n-3 PUFAs decrease anxietylike behaviors , but there is a paucity of information about their effects on anxiety in humans . In light of our observation that substance abusers have poor dietary habits and the strong association between anxiety disorders and substance use disorders , the possibility that the administration of supplements of n-3 PUFAs would decrease the anxiety level of a group of substance abusers was explored . Thirteen patients were given on a daily basis capsules containing 3 g of n-3 PUFAS ( eicosapentaenoic acid + docosahexaenoic acid ) . Eleven patients received similarly looking placebo capsules containing vegetable oil . The trial was double-blind , r and omized , and lasted 3 months . A scale assessing anxiety feelings was administered at baseline and on a monthly basis thereafter . Six PUFA group patients and 8 placebo group patients were followed for an additional 3 months after treatment discontinuation and administered the same question naire monthly . Patients who received n-3 PUFAs for 3 months showed a progressive decline in anxiety scores . This was not the case for patients who received placebos . A comparison of the 2 groups was significant ( P = 0.010 ) . Anxiety scores remained significantly decreased in the PUFA group for 3 months after treatment discontinuation . A comparison of the 2 groups followed for 6 months was also significant ( P = 0.042 ) . In conclusion , these preliminary data indicate that n-3 PUFA supplementation could be beneficial in the treatment of some patients with anxiety disorders Introduction : Recent studies found omega-3 fatty acid deficiency in brain cell membranes of schizophrenic patients . Conventional antipsychotics have many adverse reactions . Safety , availability and low price made omega-3 as a potential supplement for treatment of these patients . This study investigated the efficacy of omega-3 fatty acid as add-on treatment in schizophrenia . Material & Methods : A r and omized , double blind , placebo controlled fixed-dose , add-on clinical trial conducted over 8 weeks . 60 patients with documented schizophrenia r and omly divided into two groups : omega-3(1000 mg/day ) ( n=30 ) and placebo ( n=30 ) . Patients received omega-3 or placebo in addition to their st and ard antipsychotic treatment . Patient follow up was done using Positive and Negative syndrome Scale ( PANSS ) . Data analyzed using SPSS software v.20 . Result : At the end of 8 weeks treatment , PANSS score decreased significantly in both groups ( p<0.05 ) in comparison to baseline . Efficacy of omega-3 in decreasing general psychopathologic and total scores was significant in comparison to placebo group from 4 and 6 weeks after onset of treatment , respectively ( p<0.05 ) . Totally , omega-3 supplement therapy efficacy in comparison to sole conventional antipsychotics was 0.86 which was not significant ( p>0.05 ) . Conclusion : We found that supplemental omega-3 might increase efficacy of conventional antipsychotics in decreasing symptoms of schizophrenia . Low price , rare adverse reactions and availability of omega-3 made this substance a potential supplement in improved treatment of schizophrenia BACKGROUND There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders . METHODS We conducted a r and omized , double-blind , placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids ( .84 g/d eicosapentaenoic acid , .7 g/d docosahexaenoic acid ) supplementation in 13 children ( aged 5 to 17 years ) with autistic disorders accompanied by severe tantrums , aggression , or self-injurious behavior . The outcome measure was the Aberrant Behavior Checklist ( ABC ) at 6 weeks . RESULTS We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy , each with a large effect size . Repeated- measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity . No clinical ly relevant adverse effects were elicited in either group . CONCLUSIONS The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism Objective : To investigate whether long-chain omega-3 ( n-3 ) polyunsaturated fatty acids ( PUFAs ) improve functioning and psychiatric symptoms in young people with borderline personality disorder ( BPD ) who also meet ultra-high risk criteria for psychosis . Methods : We conducted a post hoc subgroup analysis of a double-blind , r and omized controlled trial . Fifteen adolescents with BPD ( mean age 16.2 years , [ SD 2.1 ] ) were r and omized to either 1.2 g/day n-3 PUFAs or placebo . The intervention period was 12 weeks . Study measures included the Positive and Negative Syndrome Scale , the Montgomery – Åsberg Depression Rating Scale , and the Global Assessment of Functioning . Side effects were documented with the Udvalg for Kliniske Undersøgelser . Fatty acids in erythrocytes were analyzed using capillary gas chromatography . Results : At baseline , erythrocyte n-3 PUFA levels correlated positively with psychosocial functioning and negatively with psychopathology . By the end of the intervention , n-3 PUFAs  significantly improved functioning and reduced psychiatric symptoms , compared with placebo .  Side effects did not differ between the treatment groups . Conclusions : Long-chain n-3 PUFAs should be further explored as a viable treatment strategy with minimal associated risk in young people with BPD OBJECTIVE To compare 2 omega-3 ( n-3 ) preparations enriched with eicosapentaenoic acid ( EPA ) versus docosahexaenoic acid ( DHA ) as monotherapy for major depressive disorder ( MDD ) in a 2-site , placebo-controlled , r and omized , double-blind clinical trial . METHOD 196 adults ( 53 % female ; mean [ SD ] age = 44.7 [ 13.4 ] years ) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale ( HDRS-17 ) score ≥ 15 were r and omized equally from May 18 , 2006 , to June 30 , 2011 , to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d , DHA-enriched n-3 1,000 mg/d , or placebo . RESULTS 154 subjects completed the study . Modified intent-to-treat ( mITT ) analysis ( n = 177 subjects with ≥ 1 postbaseline visit ; 59.3 % female , mean [ SD ] age 45.8 [ 12.5 ] years ) employed mixed-model repeated measures ( MMRM ) . All 3 groups demonstrated statistically significant improvement in the HDRS-17 ( primary outcome measure ) , 16-item Quick Inventory of Depressive Symptomatology-Self Report ( QIDS-SR-16 ) , and Clinical Global Improvement-Severity Scale ( CGI-S ) ( P < .05 ) , but neither n-3 preparation separated from placebo ( P > .05 ) . Response and remission rates were in the range of 40%-50 % and 30 % , respectively , for all treatments , with no significant differences between groups . One subject receiving EPA-enriched n-3 discontinued due to worsening depression , and 1 subject receiving placebo discontinued due to an unspecified " negative reaction " to pills . CONCLUSIONS Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00517036 BACKGROUND Perinatal major depressive disorder ( MDD ) , including antenatal and postpartum depression , is common and has serious consequences . This study was design ed to investigate the feasibility , safety , and efficacy of omega-3 fatty acids for  perinatal depression  in addition to supportive psychotherapy . METHODS Perinatal women with MDD were r and omized to eicosapentaenoic ( EPA ) and docosahexaenoic acids ( DHA ) , 1.9g/day , or placebo for 8weeks . A manualized supportive psychotherapy was provided to all subjects . Symptoms were assessed with the Hamilton Rating Scale for Depression ( HAM-D ) and Edinburgh Postnatal Depression Scale ( EPDS ) biweekly . RESULTS Fifty-nine women enrolled ; N = 51 had two data collection points that allowed for evaluation of efficacy . Omega-3 fatty acids were well tolerated . Participants in both groups experienced significant decreases in EPDS and HAM-D scores ( p<.0001 ) from baseline . We did not find a benefit of omega-3 fatty acids over placebo . Dietary omega-3 fatty acid intake was low among participants . LIMITATIONS The ability to detect an effect of omega-3 fatty acids may have been limited by sample size , study length , or dose . The benefits of supportive psychotherapy may have limited the ability to detect an effect of omega-3 fatty acids . CONCLUSIONS There was no significant difference between omega-3 fatty acids and placebo in this study in which all participants received supportive psychotherapy . The manualized supportive psychotherapy warrants further study . The low intake of dietary omega-3 fatty acids among participants is of concern , in consideration of the widely established health advantages in utero and in infants OBJECTIVE To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode ( MDE ) . METHOD Inclusive , double-blind , r and omized , controlled , 8-week , parallel-group trial , conducted October 17 , 2005 through January 30 , 2009 in 8 Canadian academic and psychiatric clinics . Adult out patients ( N = 432 ) with MDE ( Mini-International Neuropsychiatric Interview , version 5.0.0 , criteria ) lasting at least 4 weeks , including 40.3 % taking antidepressants at baseline , were r and omly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid ( EPA ) and 150 mg/d of docosahexaenoic acid ( DHA ) or matched sunflower oil placebo ( 2 % fish oil ) . The primary outcome was the self-report Inventory of Depressive Symptomatology ( IDS-SR(30 ) ) ; the secondary outcome was the clinician-rated Montgomery-Åsberg Depression Rating Scale ( MADRS ) . RESULTS The adjusted mean difference between treatment and placebo was 1.32 points ( 95 % CI , -0.20 to 2.84 ; P = .088 ) on the IDS-SR(30 ) and 0.97 points ( 95 % CI , -0.012 to 1.95 ; P = .053 ) on the MADRS . Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group ( P = .035 ) . For patients without comorbid anxiety disorders ( n = 204 ) , omega-3 supplementation was superior to placebo , with an adjusted mean difference of 3.17 points on the IDS-SR(30 ) ( 95 % CI , 0.89 to 5.45 ; P = .007 ) and 1.93 points ( 95 % CI , 0.50 to 3.36 ; P = .008 ) on the MADRS . CONCLUSIONS In this heterogeneous sample of patients with MDE , there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms . However , there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders . TRIAL REGISTRATION controlled-trials.com Identifier : IS RCT N47431149 Objective : The aim of the study was to determine whether docosahexaenoic acid ( DHA ) supplementation improves the behavior of children with autism . Methods : A group of 3- to 10-year-old children with autism were r and omized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months . The parents and the investigator completed the Clinical Global Impressions-Improvement scale to rate changes in core symptoms of autism after 3 and 6 months . The parents completed the Child Development Inventory and the Aberrant Behavior Checklist , and both parents and teachers completed the Behavior Assessment Scale for Children ( BASC ) at enrollment and after 6 months . Results : A total of 48 children ( 40 [ 83 % ] boys , mean age [ st and ard deviation ] 6.1 [ 2.0 ] years ) were enrolled ; 24 received DHA and 24 placebo . Despite a median 431 % increase in total plasma DHA levels after 6 months , the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I. Based on the analysis of covariance models adjusted for the baseline rating scores , parents ( but not teachers ) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group ( P = 0.04 ) , and teachers ( but not parents ) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group ( P = 0.02 ) . Conclusions : Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism . Our results may have been limited by inadequate sample size Several clinical studies showed beneficial effects of omega-3 fatty acids in major affective disorders , including resistant depression . Some antidepressants are also effective , albeit less so , in obsessive-compulsive disorder ( OCD ) . We therefore undertook a preliminary placebo-controlled cross-over trial of adjunctive eicosapentaenoic acid ( EPA ) in OCD . Eleven patients with current obsessive-compulsive disorder , who were on a stable maximally tolerated dose of SSRI with no further improvement over at least the last two months , were recruited . Subjects were r and omly allocated to begin 6 weeks of placebo ( 2 g liquid paraffin per day ) followed by 6 weeks of 2 g of EPA or EPA followed by placebo . Patients continued their prior SSRIs at the same dose . Assessment s were performed with the Yale-Brown Obsessive-Compulsive Scale ( YBOCS ) , and the Hamilton Rating Scales for depression ( HAM-D ) and anxiety ( HAM-A ) . There were no effects of order of treatment . Time had a main effect of YBOCS scores ; mean scores declined from 26.0 ( + /-5 ) to 17.6 ( + /-6 ) by week 6 on placebo and to 18.5 ( + /-4 ) on EPA . There were no effects on HAM-D and HAM-A. No clinical ly relevant side effects were reported . The results of this study suggest that adjunctive EPA is ineffective against OCD Abstract Autism spectrum disorders are a neurodevelopmental disorders with reduced cortical functional connectivity relating to social cognition . Polyunsaturated fatty acids arachidonic acid ( ARA ) and docosahexaenoic acid ( DHA ) may have key role in brain network maturation . In particularly , ARA is important in signal transduction related to neuronal maturation . Supplementation with larger ARA doses added to DHA may therefore mitigate social impairment . In a 16-week , double-blind , r and omized , placebo-controlled trial , we evaluated the efficacy of supplementation with large doses of ARA added to DHA ( n = 7 ) or placebo ( n = 6 ) in 13 participants ( mean age , 14.6 [ SD , 5.9 ] years ) . To examine underlying mechanisms underlying the effect of our supplementation regimen , we examined plasma levels of antioxidants transferrin and superoxide dismutase , which are useful markers of signal transduction . The outcome measures were the Social Responsiveness Scale and the Aberrant Behavior Checklist – Community . Repeated- measures analysis of variance revealed that our supplementation regimen significantly improved Aberrant Behavior Checklist – Community – measured social withdrawal and Social Responsiveness Scale – measured communication . Treatment effect sizes were more favorable for the treatment group compared with the placebo group ( communication : treatment groups , 0.87 vs , placebo , 0.44 ; social withdrawal : treatment groups , 0.88 , vs placebo , 0.54 ) . There was a significant difference in the change in plasma transferrin levels and a trend toward a significant difference in the change in plasma superoxide dismutase levels between the 2 groups . This preliminary study suggests that supplementation with larger ARA doses added to DHA improves impaired social interaction in individuals with autism spectrum disorder by up-regulating signal transduction 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 r and omly assigned to receive either 3 g/day of ethyl EPA ( N=43 ) or placebo ( N=44 ) in a 16-week , double-blind supplementation trial . Assessment s 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 Background : Phytoestrogens offer a possible alternative to hormone replacement therapy . Flax seed contains large quantities of a phytoestrogen precursor , secoisolariciresinol diglucoside ( SDG ) , as well as large quantities of α-linolenic acid ; these factors may be protective against vascular disease . We have previously shown that the rise in blood pressure during mental stress is a strong predictor of atherosclerosis progression . Methods : 35 postmenopausal women with vascular disease , 62 ± 8 years of age , were treated in a r and om-sequence double-blind Latin square crossover study comparing three strains of flax seed : Fl and ers ( low in lignan and high in α-linolenic acid ) , Linola 989 ( high in lignan and low in α-linolenic acid ) and AC Linora ( intermediate in both lignan and α-linolenic acid ) . Results : Compared to the pre-treatment baseline diet , all three strains of flax  significantly reduced blood pressure during mental stress induced by a frustrating cognitive task ( Stroop color-word interference task ) ( p = 0.004 ) . Linola 989 , the strain highest in lignan and lowest in α-linolenic acid , was associated with the least increase in peripheral resistance during stress , the greatest reduction in plasma cortisol during stress and the smallest increase in plasma fibrinogen during mental stress . Conclusion : Flax phytoestrogens ameliorate certain responses to stress and thus may afford protection against atherosclerosis ; this hypothesis should be tested in clinical trials OBJECTIVE To determine whether docosahexaenoic acid ( DHA ) supplementation for 4 months decreases the symptoms of  attention-deficit/hyperactivity disorder ( ADHD ) .  STUDY DESIGN Sixty-three 6- to-12-year-old children with ADHD , all receiving effective maintenance therapy with stimulant medication , were assigned r and omly , in a double-blind fashion , to receive DHA supplementation ( 345 mg/d ) or placebo for 4 months . Outcome variables included plasma phospholipid fatty acid patterns , scores on laboratory measures of inattention and impulsivity ( Test of Variables of Attention , Children 's Color Trails test ) while not taking stimulant medication , and scores on parental behavioral rating scales ( Child Behavior Checklist , Conners ' Rating Scale ) . Differences between groups after 4 months of DHA supplementation or placebo administration were determined by analysis of variance , controlling for age , baseline value of each outcome variable , ethnicity , and ADHD subtype . RESULTS Plasma phospholipid DHA content of the DHA-supplemented group was 2.6-fold higher at the end of the study than that of the placebo group ( 4.85 + /- 1.35 vs 1.86 + /- 0.87 mol % of total fatty acids ; P < .001 ) . Despite this , there was no statistically significant improvement in any objective or subjective measure of ADHD symptoms . CONCLUSION A 4-month period of DHA supplementation ( 345 mg/d ) does not decrease symptoms of ADHD BACKGROUND Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid ( PUFA ) on patients with attention-deficit hyperactivity disorder ( ADHD ) , changes in plasma PUFA composition were not always assessed following n-3 supplementation . Furthermore , no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD . OBJECTIVES To determine fatty acid ( FA ) composition , and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children . PATIENTS AND METHODS The Strengths and Weaknesses in ADHD and Normal Behaviors ( SWAN ) and Conners ' question naires were used to assess changes in ADHD symptoms in 37 children ( only 26 children completed the study from zero to 16 weeks ) . They were divided into two groups ( A and B ) , and participated in a 16-week , double-blind , one-way , crossover r and omized study . In the first phase , group A received the n-3 PUFA supplement and group B received n-6 PUFA ( sunflower oil ) as a placebo . During the second phase , group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study . RESULTS FA differences between groups were observed in the 26 patients . Supplementation with n-3 PUFA result ed in significant increases in eicosapentaenoic and docosahexaenoic acids in group A , while group B was enriched with alpha-linolenic , gamma-linolenic and homo-gamma-linolenic acids . The n-3 PUFA supplement was tolerated without any adverse effects . A statistically significant improvement in symptoms was noted based on the parent version of the Conners ' question naire from baseline to the end of phase 1 , and this amelioration continued from phases 1 to 2 , although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2 . A subgroup of eight patients ( four in each group ) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement , particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders , Fourth edition , total Conners ' subscales . CONCLUSIONS A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control . The data of the present study also supported n-3 PUFA  safety and tolerability , but limited changes were noted in the FA profile in French Canadians with ADHD OBJECTIVE Mounting evidence indicates that low levels of n-3 polyunsaturated fatty acids ( PUFAs ) play a role in the pathophysiology of a large number of psychiatric disorders . In light of the suboptimal n-3 PUFAs intake due to poor dietary habits among substance abusers and the strong associations between aggression , anxiety and substance use disorders we examined if insurance of adequate intakes of n-3 PUFAs with supplementation would decrease their anger and anxiety scores . METHOD Substance abusers ( n=22 ) were assigned to either 3 g of n-3 PUFAs , mainly eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) or soybean oil in identically looking capsules . The trial was double-blind , r and omized and lasted 3 months . Anger and anxiety scales were administered at baseline and once a month thereafter . Blood sample s were collected at baseline and at the end of the trial . RESULTS Patients ' dietary intakes of n-3 PUFAs fell below recommended levels . Assignment to n-3 PUFA treatment was accompanied by significant decreases in anger and anxiety scores compared to placebo assignment . These changes were associated with increases in plasma levels of both EPA and DHA but an increase in EPA was more robustly correlated with low end-of-trial anxiety scores and an increase in DHA was more robustly correlated with low end-of-trial anger scores . CONCLUSION These pilot data indicate that ensuring adequate n-3 PUFA intake via supplementation benefits substance abusers by reducing their anger and anxiety levels . The strong correlations between an increase in plasma EPA and lower anxiety scores and between an increase in plasma DHA and lower anger scores suggests a need for the further exploration of the differential responses to these two n-3 PUFAs in different psychiatric conditions CONTEXT The use of antipsychotic medication for the prevention of psychotic disorders is controversial . Long-chain omega-3 ( omega-3 ) polyunsaturated fatty acids ( PUFAs ) may be beneficial in a range of psychiatric conditions , including schizophrenia . Given that omega-3 PUFAs are generally beneficial to health and without clinical ly relevant adverse effects , their preventive use in psychosis merits investigation . OBJECTIVE To determine whether omega-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis . DESIGN R and omized , double-blind , placebo-controlled trial conducted between 2004 and 2007 . SETTING Psychosis detection unit of a large public hospital in Vienna , Austria . PARTICIPANTS Eighty-one individuals at ultra-high risk of psychotic disorder . INTERVENTIONS A 12-week intervention period of 1.2-g/d omega-3 PUFA or placebo was followed by a 40-week monitoring period ; the total study period was 12 months . MAIN OUTCOME MEASURES The primary outcome measure was transition to psychotic disorder . Secondary outcomes included symptomatic and functional changes . The ratio of omega-6 to omega-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition . RESULTS Seventy-six of 81 participants ( 93.8 % ) completed the intervention . By study 's end ( 12 months ) , 2 of 41 individuals ( 4.9 % ) in the omega-3 group and 11 of 40 ( 27.5 % ) in the placebo group had transitioned to psychotic disorder ( P = .007 ) . The difference between the groups in the cumulative risk of progression to full-threshold psychosis was 22.6 % ( 95 % confidence interval , 4.8 - 40.4 ) . omega-3 Polyunsaturated fatty acids also significantly reduced positive symptoms ( P = .01 ) , negative symptoms ( P = .02 ) , and general symptoms ( P = .01 ) and improved functioning ( P = .002 ) compared with placebo . The incidence of adverse effects did not differ between the treatment groups . CONCLUSIONS Long-chain omega-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states . Trial Registration clinical trials.gov Identifier : NCT00396643 OBJECTIVE The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed . STUDY DESIGN Mothers who planned to breast-feed their infants were assigned r and omly in a double-masked fashion to receive either docosahexaenoic acid ( approximately 200 mg/d ) or placebo for the first 4 months after the delivery . Major outcome variables included plasma phospholipid fatty acid patterns and scores on a self-rating question naire of current depression symptoms . A structured clinical interview of depression , scores on another self-rating question naire of depression symptoms , and a laboratory measure of information processing were obtained in subgroups of the total population . RESULTS Plasma phospholipid contents of docosahexaenoic acid at baseline were 3.15 + /- 0.78 and 3.31 + /- 0.70 ( mg/dL of total fatty acids ) in the docosahexaenoic acid and placebo groups , respectively . After 4 months , the plasma phospholipid docosahexaenoic acid content of the docosahexaenoic acid group was 8 % higher ( 3.40 + /- 0.97 mg/dL ) , whereas that of the placebo group was 31 % lower ( 2.27 + /- 0.87 mg/dL ) . Despite the higher plasma phospholipid docosahexaenoic acid content of the supplemented group after 4 months , there was no difference between groups in either self-rating or diagnostic measures of depression ; information processing scores of the two groups also did not differ . CONCLUSION Docosahexaenoic acid supplementation ( approximately 200 mg/d ) for 4 months after the delivery prevented the usual decline in plasma phospholipid docosahexaenoic acid content of women who breastfeed but did not influence self-ratings of depression , diagnostic measures of depression , or information processing OBJECTIVE Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder . The authors studied a specific omega-3 fatty acid , the ethyl ester of eicosapentaenoic acid ( E-EPA ) , as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy . METHOD Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week , parallel-group , double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy .  Seventeen of the patients were women , and three were men . RESULTS Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment . CONCLUSIONS It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own Evidence that the metabolism of phospholipids and polyunsaturated fatty acids ( PUFA ) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation . An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies . The first study was design ed to distinguish between the possible effects of two different n-3 PUFA : eicosapentaenoic acid ( EPA ) and docohexaenoic acid ( DHA ) .  Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA , DHA or placebo for 3 months . Improvement on EPA measured by the Positive and Negative Syndrome Scale ( PANSS ) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS . EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures . In the second placebo-controlled study , EPA was used as a sole treatment , though the use of antipsychotic drugs was still permitted if this was clinical ly imperative . By the end of the study , all 12 patients on placebo  , but only eight out of 14 patients on EPA  , were taking antipsychotic drugs . Despite this , patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study . It is concluded that EPA may represent a new treatment approach to schizophrenia , and this requires investigation by large-scale placebo-controlled trials BACKGROUND It has been hypothesized that depletion of cell membrane n3 polyunsaturated fatty acids ( PUFA ) , particularly docosahexanoic acid ( DHA ) , may be of etiological importance in depression . METHODS We measured the fatty acid composition of phospholipid in cell membranes from red blood cells ( RBC ) of 15 depressive patients and 15 healthy control subjects . RESULTS Depressive patients showed significant depletions of total n3 PUFA and particularly DHA . Incubation of RBC from control subjects with hydrogen peroxide abolished all significant differences between patients and controls . CONCLUSIONS These findings suggest that RBC membranes in depressive patients show evidence of oxidative damage . Possible interpretations , and implication s for the etiology and treatment of depression , are discussed OBJECTIVE This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid ( DHA ) for the treatment of major depression . METHOD Thirty-six depressed patients were r and omly assigned to receive DHA , 2 g/day , or placebo for 6 weeks . Response was defined a priori as a > or = 50 % reduction in the score on the Montgomery-Asberg Depression Rating Scale .  Thirty-five participants were evaluable ; 18 received DHA , and 17 received placebo . RESULTS Response rates were 27.8 % in the DHA group and 23.5 % in the placebo group . The difference in response rates between groups did not reach statistical significance . CONCLUSIONS This trial failed to show a significant effect of DHA monotherapy in subjects with major depression Background : Controversy over the efficacy of n-3 polyunsaturated fatty acids ( PUFAs ) in depression continues to this day . The present study investigated the hypothesis that n-3 PUFA supplementation reduces depressive symptoms in Korean patients with major depressive disorder . Methods : In a r and omized , double-blind , placebo-controlled , 12-week , parallel-group trial , 35 patients with Center for Epidemiological Studies Depression Scale Korean version ( CES-D-K ) scores ≥25 and depression confirmed by a psychiatrist were assigned to take either 3 capsules of n-3 PUFAs ( 1,140 mg of EPA + 600 mg of DHA ; n = 18 ) or placebo ( olive oil + safflower oil ; n = 17 ) . Results : Supplementation with n-3 PUFAs significantly reduced Clinical Global Impression Improvement ( CGI-I ) scores as compared with intake of placebo using intention-to-treat analysis with last-observation-carried-forward after adjusting for energy , fat , and fish intake . However , the CES-D-K , Hamilton Depression Rating Scale-17 , and Clinical Global Impression Scale scores did not significantly differ between the n-3 PUFA and placebo groups . After supplementation with n-3 PUFAs , the erythrocyte levels of n-3 PUFAs were significantly increased , but n-6 PUFA levels were decreased . Conclusions : n-3 PUFAs demonstrated an advantage over placebo that did not reach clinical significance , although CGI-I score was significantly decreased in the n-3 PUFA group as compared with the placebo group BACKGROUND Epidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid ( EPA ) alleviates unipolar depression . AIMS To examine the efficacy of EPA in treating depression in bipolar disorder . METHOD In a12-week , double-blind study individuals with bipolar depression were r and omly assigned to adjunctive treatment with placebo ( n=26 ) or with 1 g/day ( n=24 ) or 2 g/day ( n=25 ) of ethyl-EPA . Primary efficacy was assessed by the Hamilton Rating Scale for Depression ( HRSD ) , with changes in the Young Mania Rating Scale and Clinical Global Impression Scale ( CGI ) as secondary outcome measures . RESULTS There was no apparent benefit of 2 g over 1 g ethyl-EPA daily . Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD ( P=0.04 ) and the CGI ( P=0.004 ) scores . Both doses were well tolerated . CONCLUSIONS Adjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression Objective : The aim of the study was to assess omega 3/6 fatty acids ( eye q ) in attention deficit hyperactivity disorder ( ADHD ) . Method : The study included a r and omized , 3-month , omega 3/6 placebo-controlled , one-way crossover trial with 75 children and adolescents ( 8—18 years ) , followed by 3 months with omega 3/6 for all .  Investigator-rated ADHD Rating Scale — IV and Clinical Global Impression ( CGI ) scale were outcome measures . Results : A majority did not respond to omega 3/6 treatment . However , a subgroup of 26 % responded with more than 25 % reduction of ADHD symptoms and a drop of CGI scores to the near-normal range . After 6 months , 47 % of all showed such improvement . Responders tended to have ADHD inattentive subtype and comorbid neurodevelopmental disorders . Conclusion : A subgroup of children and adolescents with ADHD , characterized by inattention and associated neurodevelopmental disorders , treated with omega 3/6 fatty acids for 6 months responded with meaningful reduction of ADHD symptoms . ( J. of Att . Dis . 2009 ; 12(5 ) 394 - 401 BACKGROUND The results of pilot trials suggest that omega-3 fatty acids may have efficacy in the treatment of mood symptoms in bipolar disorder . METHODS We conducted a 4-month , r and omized , placebo-controlled , adjunctive trial of ethyl-eicosapentanoate ( EPA ) 6 g/day in the treatment of bipolar depression and rapid cycling bipolar disorder . Subjects were receiving mood-stabilizing medications at therapeutic doses or plasma concentrations . The measures of efficacy were early study discontinuation , changes from baseline in depressive symptoms ( Inventory for Depressive Symptomology total score ) and in manic symptoms ( Young Mania Rating Scale total score ) , and manic exacerbations ( " switches " ) . We also measured side effects and bleeding time , a biomarker of drug action . RESULTS Overall , there were no significant differences on any outcome measure between the EPA and placebo groups . CONCLUSIONS This study did not find overall evidence of efficacy for adjunctive treatment with EPA 6 g/day in out patients with bipolar depression or rapid cycling bipolar disorder Our recent pilot study has shown that the supplementation of omega-3 fatty acids ( fish oil ) immediately after a traumatic event may be effective toward the secondary prevention of post-traumatic disorder ( PTSD ) . To lay the groundwork for addressing the mechanism by which omega-3 fatty acids can prevent PTSD , we analyzed its psychophysiological data . The psychophysiological data included heart rate , skin conductance , and continuous blood pressure during patient subjection to startling tones and idiographic trauma-related cues . Of the 8 patients , 1 met the diagnostic criteria for PTSD . Compared to the seven patients without PTSD , one patient with PTSD showed relatively large reactivity to the startle tones . In contrast , this patient did not show large reactivity to the trauma-related cue during script-driven imagery . The combination of psychophysiological measurements in our r and omized control trial should shed light on the underlying mechanisms by which omega-3 fatty acids can prevent PTSD OBJECTIVE The authors hypothesized that changes in brain membrane composition result ing from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity , as detected by reductions in T(2 ) values . METHOD Women with bipolar disorder ( N=12 ) received omega-3 fatty acids for 4 weeks . A cohort of bipolar subjects ( N=9 ) and a group without bipolar disorder ( N=12 ) did not receive omega-3 fatty acids .  T(2 ) values were acquired at baseline and after 4 weeks . RESULTS Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2 ) . There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts . CONCLUSIONS Omega-3 fatty acids lowered T(2 ) values , consistent with the hypothesis that the fluidity of cell membranes was altered . Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids , as reflected in T(2 ) values Converging evidence suggests that omega-3 polyunsaturated fatty acids have aetiological importance in depression . To determine the effect of adding fish oil to existing therapy in participants who were being treated for depression in a community setting , 77 participants were r and omly assigned to receive 8 g of either fish or olive oil per day in addition to their existing therapy . Fifty-nine ( 77 % ) participants completed 12 weeks of treatment . Dietary , biochemical and lifestyle factors were measured throughout the study . Mood was assessed using the Short Form Hamilton Depression Rating Scale ( HDRS-SF ) and the Beck Depression Inventory II . Sample size calculations were based on the HDRS-SF . Intention-to-treat and per protocol analyses were carried out using residual maximum likelihood . There was no evidence that fish oil improved mood when compared to the placebo oil , despite an increase in circulating omega-3 polyunsaturated fatty acids . However , mood improved significantly in both groups within the first 2 weeks of the study ( P<0.001 ) and this improvement was sustained throughout . In conclusion , fish oil was no more effective than the control as an add-on therapy for depression in this setting Delayed language development may be an early indicator of autism spectrum disorder ( ASD ) . Early intervention is critical for children with ASD , and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development , a secondary trial outcome , in children at risk for ASD . We r and omized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months , and measured their language abilities at baseline and after supplementation . Gesture use , but not word production , increased for children in the treatment group more than children in the placebo group . These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD Observational studies suggest association between low concentrations of omega-3 family fatty acids and greater risk for post-partum depression ( PPD ) .  The objective was to investigate the effect of unbalanced dietary intake of omega-6/omega-3 ratio > 9:1 in the prevalence for PPD . The study comprises a prospect i ve cohort with four waves of follow-up during pregnancy and one following delivery . PPD was evaluated according to the Edinburgh Post-partum Depression Scale ( PPD ≥ 11 )  in 106 puerperae between 2005 and 2007 , in Rio de Janeiro , Brazil . Independent variables included socio-demographic , obstetric , pre-pregnancy body mass index ( BMI ) and dietary intake data , which were obtained by means of a food frequency question naire in the first trimester of pregnancy . Statistical analysis involved calculation of PPD prevalence and multivariate Poisson regression with robust variance . PPD prevalence amounted to 26.4 % [ n = 28 ; confidence interval ( CI ) 95 % : 18.0 - 34.8 ] , and higher prevalences of PPD were observed in women who consumed an omega-6/omega-3 ratio > 9:1 ( 60.0 % ) and in those with pre-pregnancy BMI < 18.5 kg/m(2 ) ( 66.7 % ) . These variables held as factors associated to PPD in the multivariate model , elevating the chances of occurrence of the outcome in 2.50 ( CI 95 % : 1.21 - 5.14 ) and 4.01 times ( CI 95 % : 1.96 - 8.20 ) , respectively . Analyses were adjusted for age , schooling , pre-pregnancy BMI , lipids consumption and time elapsed since delivery . It verified an association between omega-6/omega-3 ratio above 9:1 , the levels recommended by the Institute of Medicine , and the prevalence of PPD . These results add to the evidence regarding the importance of omega-6 and omega-3 fatty acids in the regulation of mental health mechanisms Dietary deficiencies in essential omega-3 polyunsaturated fatty acids derived from fish are associated with depression and some fish oils may have therapeutic benefits . We aim ed to determine whether taking tuna fish oil confers any additional benefit to conventional outpatient treatment for major depression . A r and omized double-blind placebo-controlled four-month trial comparing tuna fish oil versus placebo was conducted on 83 out patients with major depression . Despite large reductions in depression there were no significant differences at any assessment time point between patients receiving fish oil compared to placebo .  Red blood cell incorporation of fatty acids indicated good compliance with oil supplementation , although this sample was not initially deficient in omega-3s . This particular dose and type of fish oil conferred no additional benefit to conventional treatment of depression in this sample . Future studies could target participants with pre-existing omega-3 deficiency and appraise alternate enriched types and higher doses of omega-3 supplementation OBJECTIVE To compare the feasibility of blinding and the perceived risk of unblinding in trials evaluating  pharmacologic ( PT ) and nonpharmacologic treatments ( NPT ) of hip or knee osteoarthritis . STUDY DESIGN AND SETTING Two independent review ers assessed the feasibility of blinding  patients , care providers , and outcome assessors , the perceived risk of unblinding , and whether blinding was reported in 110 reports of r and omized controlled trials ( RCTs ) evaluating PT and NPT in patients with hip or knee osteoarthritis . RESULTS Blinding was considered to be possible less often in NPT trials than in PT trials for patients ( 42 vs. 96 % ; P < .001 ) , care providers ( 12 vs. 96 % ; P < .001 ) , and outcome assessors ( 34 vs. 98 % ; P < .001 ) . When blinding was judged feasible , the perceived risk of unblinding was more often considered moderate or important in NPT than PT trials for patients ( 35 vs. 14 % , P=.02 ) and outcome assessors ( 44 vs. 10 % , P=.0004 ) . When blinding was judged feasible , it was reported less often in NPT reports than in PT reports for patients ( 46 vs. 98 % , P < .001 ) , care providers ( 43 vs. 83 % , P=.03 ) , and outcome assessors ( 72 vs. 98 % , P=.0006 ) . CONCLUSION Blinding appears to be more difficult to achieve and unblinding may occur more often in NPT than PT trials BACKGROUND In depressed patients , low blood levels of eicosapentaenoic acid are seen . We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients . METHODS We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a st and ard antidepressant .  Patients were r and omized on a double-blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1 , 2 , or 4 g/d for 12 weeks in addition to unchanged background medication . Patients underwent assessment using the 17-item Hamilton Depression Rating Scale , the Montgomery-Asberg Depression Rating Scale , and the Beck Depression Inventory . RESULTS Forty-six ( 88 % ) of 52 patients receiving ethyl-eicosapentaenoate and 14 ( 78 % ) of 18 patients receiving placebo completed the 12-week study with no serious adverse events . The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales . In the intention-to-treat group , 5 ( 29 % ) of 17 patients receiving placebo and 9 ( 53 % ) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50 % reduction on the Hamilton Depression Rating Scale score . In the per- protocol group , the corresponding figures were 3 ( 25 % ) of 12 patients for placebo and 9 ( 69 % ) of 13 patients for the 1-g/d group . The 2-g/d group showed little evidence of efficacy , whereas the 4-g/d group showed nonsignificant trends toward improvement . All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo , with strong beneficial effects on items rating depression , anxiety , sleep , lassitude , libido , and suicidality . CONCLUSION Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating  depression in patients who remained depressed despite adequate st and ard therapy Objective This study aim ed to test the effects of omega-3 fatty acids ( O3FA ) , given as fish oil capsules , with and without oral cytidine ( CYT ) , a pyrimidine with reported pre clinical and clinical antidepressant-like effects , in patients with bipolar disorder ( BD ) . Methods A total of 45 out patients with diagnosed BD ( type I ) according to the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition – Text Revision , were recruited for this 4-month , r and omized , double-blind , placebo-controlled , add-on study . Treatment groups were ( 1 ) oral CYT + O3FA , ( 2 ) placebo + O3FA , and ( 3 ) placebo + placebo control . O3FA was given 2 g twice a day and CYT was administered as 1 g twice a day . Results There was no statistically significant difference among the groups in the primary outcome : study retention . Clinical measures improved in all treatment groups , and there were no significant differences between groups , including change in probability of symptoms of depression or mania , change in positive ratings of depression or mania , or change in Global Assessment of Functioning scores . Neither CYT + O3FA nor placebo + O3FA treatment was superior to placebo treatment . Rather , there was a statistically nonsignificant trend for both groups treated with O3FA to do worse than the placebo group . Conclusions Despite pre clinical studies suggesting that the effect of O3FA might be augmented with pyrimidines , add-on CYT did not substantially improve mood symptoms in BD . In addition , although a power analysis indicated that the sample size would be adequate to see beneficial effects similar to those previously reported , O3FA treatment by itself was not superior to placebo for BD OBJECTIVE We previously reported that administration of fish oil rich in docosahexaenoic acid ( DHA ) increased the plasma ratio of epinephrine to norepinephrine ( NE ) at rest in young adults who were under chronic stress and that this effect was achieved mainly through depression of NE . However , not many reports have documented the effects of eicosapentaenoic acid ( EPA ) and DHA on blood catecholamine levels in healthy humans . Therefore , we performed another intervention study to test their effect on catecholamines with healthy subjects under no chronic stress . METHODS Twenty-one healthy young adults ( 15 men and 6 women ) were r and omly assigned to an omega-3 group ( n = 9 ) or a control group ( n = 12 ) in a double-blind manner . Twenty capsules of shellfish-derived lipids containing 762 mg of EPA plus DHA per day were administered to the omega-3 group for 2 mo . The controls took the same amount of placebo capsules . Fasting blood sample s after a 30-min rest with a catheter in a forearm vein were obtained at the start and the end of the study for catecholamine measurements . RESULTS  EPA but not DHA concentrations in red blood cells significantly increased in the omega-3 group compared with the control group ( P < 0.001 ) . Plasma NE concentrations were significantly decreased in the omega-3 group ( from 1.49 + /- 0.39 nmol/L to 1.05 + /- 0.14 nmol/L ) compared with the control group ( from 1.12 + /- 0.24 nmol/L to 1.39 + /- 0.32 nmol/L ) with analysis of covariance ( P < 0.001 ) . The differences remained significant ( P = 0.01 ) even after deletion of three subjects in the omega-3 group who had the highest baseline NE values and one in the control group who had the lowest baseline NE value to nullify a significant baseline differences in NE between groups . CONCLUSION This study demonstrated that EPA plus DHA supplementation lowered plasma NE concentrations in normal volunteers even at the small dose of 762 mg of EPA plus DHA per day . This effect of EPA plus DHA to lower plasma NE concentrations may be important to underst and some of the effects of fish oils on diseases OBJECTIVE Exaggerated cardiovascular reactivity predicts cardiovascular morbidity and mortality . Some evidence suggests that omega-3 fatty acids improve cardiovascular function . The objective of this study was to examine the influence of an acute low dose of long-chain omega-3 fatty acids on young , healthy individuals . METHODS Participants ( n=34 ) were r and omly assigned to either 21-days of omega-3 fatty acids ( 1.4 g EPA and DHA ) or matched placebo .  Cardiovascular measurements were obtained in the laboratory during baseline and during a st and ard mental arithmetic task , where participants were instructed to engage in serial subtractions by 17s from a four-digit number and cardiovascular reactivity to the task was calculated . RESULTS Mean arterial pressure reactivity was significantly reduced by supplementation ( F(1,32)=5 . 12 , p=.03 , η(2)=.144 ) but not by placebo . CONCLUSION Supplementation of omega-3 fatty acids may reduce cardiovascular reactivity to stress Objective : Epidemiological , biological marker and treatment studies , as well as neuroscientific theories , indicate a possible link between omega-3 fatty acids and perinatal depression ( PND ) . Hence the aim of the present study was to assess whether omega-3 fatty acid treatment is superior to placebo in the treatment of PND . Method : A double-blind r and omized placebo-controlled trial was undertaken . Women with major depression during the perinatal period received either fish oil or placebo for six weeks . Changes in depression scores were recorded weekly . Results : A total of 26 subjects were recruited and there was no significant difference in depression scores between those receiving fish oil and those receiving the placebo . Conclusions : This is formally a negative study , suggesting that there is no benefit for omega-3 fatty acids over placebo in treating PND . The reason could be that the study was underpowered due to recruitment difficulties and therefore we suggest that it may be unwise to interpret this result as conclusive . Omega-3 is a natural product that is a safe and well-tolerated treatment . Further research is therefore needed in this area to establish whether omega-3 fatty acids are an effective treatment for PND The objective was to test effects of ethyl eicosapentaenoate ( E-E ) on persistent ongoing symptoms in patients receiving different types of anti-schizophrenic drugs , typical antipsychotics , new atypical antipsychotics , and clozapine . 115 patients with DSM-IV-defined schizophrenia were studied , 31 on clozapine , 48 on new atypical drugs and 36 on typical antipsychotics . Placebo or 1 , 2 or 4 g/day of E-E was given for 12 weeks in addition to the background medication . The main assessment was change from baseline to 12 weeks on the PANSS and its sub-scales . There were no treatment-related side effects or adverse biochemical or haematological effects . Patients on 2 and 4 g/day E-E showed significant reductions in triglyceride levels which had been elevated by clozapine . In patients given 2 g/day E-E there were improvements on the PANSS and its sub-scales , but there was also a large placebo effect in patients on typical and new atypical antipsychotics and no difference between active treatment and placebo . In patients on clozapine , in contrast , there was little placebo response , but a clinical ly important and statistically significant effect of E-E on all rating scales . This effect was greatest at 2 g/day . There was a positive relationship between improvement on rating scales and rise in red blood cell arachidonic acid concentration There is emerging evidence that Omega-3 polyunsaturated fatty acids ( PUFA ) supplements can decrease aggression . However , experimental studies with adults from non-specific population s are scarce . We hypothesized that Omega-3 supplements would decrease self-reported aggression among non- clinical participants . In a double-blind r and omized trial , two groups of participants ( N = 194 ) aged 18 - 45 from the general population followed a 6-weeks treatment with 638 mg docosahexaenoic acid ( DHA ) and 772 mg eicosapentaenoic acid ( EPA ) per day or the equivalent quantity of copra oil ( placebo ) .  Self-reported aggressiveness was measured at baseline and after the 6-week treatment period . Findings showed that Omega-3 supplements significantly decreased self-reported aggressiveness at the end of the 6-week period ( d = 0.31 ) . In conclusion , this experiment indicates that Omega-3 administration has beneficial effects in reducing aggression among the general population OBJECTIVE Reports are mixed on the efficacy of omega-3 fatty acids ( O3FA ) for the treatment of major depressive disorder ( MDD ) , with only limited data in adolescents . The present trial aim ed to investigate systematic ally the efficacy of O3FA as a monotherapy , compared to a placebo , in adolescents with MDD . Secondarily , we explored O3FA effects on anhedonia , irritability , and suicidality-all key features of adolescent MDD . METHODS Fifty-one psychotropic medication-free adolescents with DSM-IV-TR diagnoses of MDD ( aged 12 - 19 years ; 57 % female ) were r and omized to receive O3FA or a placebo for 10 weeks . Data were collected between January 2006 and June 2013 .  O3FA and a placebo were administered on a fixed-flexible dose titration schedule based on clinical response and side effects . The initial dose of 1.2 g/d was increased 0.6 g/d every 2 weeks , up to a maximum of 3.6 g/d . Clinician-rated and self-rated depression severity , along with treatment response , served as primary outcome measures . Additionally , we examined O3FA effects on depression-related symptoms , including anhedonia , irritability , and suicidality . Treatment differences were analyzed via intent-to-treat analyses . RESULTS O3FA were not superior to a placebo on any clinical feature , including depression severity and levels of anhedonia , irritability , or suicidality . Additionally , response rates were comparable between treatment groups . Within-treatment analyses indicated that both treatments were associated with significant improvement in depression severity on self- ( O3FA : t = -4.38 , P < .001 ; placebo : t = -3.52 , P = .002 ) and clinician ( O3FA : t = -6.47 , P < .001 ; placebo : t = -8.10 , P < .001 ) ratings . CONCLUSIONS In adolescents with MDD , O3FA do not appear to be superior to placebo . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00962598 BACKGROUND Extant literature shows that adjuvant omega-3-polyunsaturated fatty acids ( O3PUFAs ) to a st and ard antidepressant medication impacts favorably on symptoms of depression in participants with major depressive disorders ( MDD ) . The aim of the present study was to investigate , if and to what extent compared to placebo adjuvant O3PUFAs had a favorable impact on symptoms of depression , anxiety , sleep and emotion regulation among out patients with MDD . METHOD A total of 50 out patients ( mean age : M = 42.46 ; 68 % females ) took part in this r and omized , double-blind and placebo-controlled study . They were r and omly assigned either to the O3PUFA- or to the placebo-condition . St and ard medication was sertraline at therapeutic dosages . At baseline , six weeks and 12 weeks later at study completion participants completed question naires covering symptoms of depression , anxiety sensitivity , intolerance of uncertainty , sleep disturbances , and emotion regulation . In parallel , experts blind to participants ' group assignment rated participants ' depression with the Montgomery-Asberg Depression Scale . RESULTS Symptoms of depression ( self- and experts ' ratings ) decreased over time , but more so in the O3PUFA condition , compared to the placebo condition . Likewise , anxiety sensitivity , intolerance of uncertainty and sleep disturbances improved , but again more so in the O3PUFA condition . Further , regulation and control of emotions and perception of other 's emotions improved over time , but more so in the O3PUFA condition . CONCLUSIONS Among out patients with MDD , and compared to placebo , adjuvant O3PUFAs to a st and ard medication improved not only symptoms of depression , but also dimensions of anxiety and sleep , and above all patients ' competencies to regulate their emotions OBJECTIVE To evaluate the effectiveness and tolerability of omega-3 polyunsaturated fatty acid ( PUFA ) supplementation for treatment of trait anxiety among adolescent females with restrictive anorexia nervosa ( AN ) . METHOD A pilot double-blind , placebo-controlled r and omized trial of adolescent females with AN ( N = 24 ) entering Partial Hospitalization Program ( PHP ) from January 2015 to February 2016 . Participants were r and omized to four daily PUFA ( 2,120 mg eicosapentaenoic acid/600 mg docosohexaenoic acid ) or placebo capsules for 12 weeks . A 9-item question naire of side effect frequency assessed medication tolerability . The Beck Anxiety Inventory-Trait measured anxiety at baseline , 6 , and 12 weeks . Linear mixed models evaluated associations between r and omization group and study outcomes . Twenty-two and 18 participants completed 6 and 12 weeks of data collection , respectively . RESULTS Medication side effect scores were low and were not significantly different between r and omization groups at Week 6 ( p = .20 ) or 12 ( p = .41 ) . Mean trait anxiety score significantly ( p < .01 ) decreased from baseline to 12 weeks in both groups , and the rate of change over the course of time did not differ between omega-3 PUFA and placebo groups ( p = .55 ) . CONCLUSION Omega-3 PUFA supplementation was well tolerated in adolescent females with AN . Although power to detect differences was limited , we found no evidence that omega-3 PUFA benefited anxiety beyond nutritional restoration Irritability and hyperactivity are common in children with Autism Spectrum Disorder ( ASD ) . Because pharmacological treatments may have adverse effects , and despite limited evidence , caregivers/parents often use dietary supplements such as vitamin D and omega-3 fatty acids to address these behavioural symptoms . As a secondary objective of the VIDOMA ( Vitamin D and Omega-3 in ASD ) trial , we evaluated the efficacy of vitamin D , omega-3 long chain polyunsaturated fatty acid [ omega-3 LCPUFA ; docosahexaenoic acid ( DHA ) ] , or both on irritability and hyperactivity .  New Zeal and children with ASD ( aged 2.5 - 8 years ) participated in a 12-month r and omized , double-blind , placebo-controlled trial of vitamin D ( 2000 IU/day , VID ) , omega-3 LCPUFA ( 722 mg/day DHA , OM ) , or both ( 2000 IU/day vitamin D + 722 mg/day DHA , VIDOM ) . The primary outcomes were the Aberrant Behaviour Checklist ( ABC ) domains of irritability and hyperactivity . Biomarkers ( serum 25-hydroxyvitamin D [ 25(OH)D ] and omega-3 index ) and primary outcomes were measured at baseline and 12-months . Out of 111 children who completed baseline data collection , 66 % completed the study ( VID = 19 , OM = 23 , VIDOM = 15 , placebo = 16 ) . After 12 months , children receiving OM ( -5.0 ± 5.0 , P = 0.001 ) and VID ( -4.0±4.9 , P = 0.01 ) had greater reduction in irritability than placebo ( 0.8±6.1 ) . Compared to placebo , children on VID also had greater reduction in hyperactivity ( -5.2±6.3 vs. -0.8±5.6 , P = 0.047 ) . Serum 25(OH)D concentration ( nmol/L , mean±SD ) increased by 27±14 in VID and by 36±17 in VIDOM groups ( P < 0.0001 ) , and omega-3 index ( % , median ( 25th , 75th percentiles ) ) by 4.4 ( 3.3 , 5.9 ) in OM and by 4.0 ( 2.0 , 6.0 ) in VIDOM groups ( P < 0.0001 ) , indicating a good compliance rate . The results indicate that vitamin D and omega-3 LCPUFA reduced irritability symptoms in children with ASD . Vitamin D also reduced hyperactivity symptoms in these children BACKGROUND This study assessed whether a combined intervention of omega-3 polyunsaturated fatty acids ( PUFAs ) and psychoeducation better improved  mild to moderate depression in workers compared to psychoeducation alone . METHODS This study was a double-blinded , parallel group , r and omized controlled trial that compared the intervention group , receiving omega-3 fatty acids , with a control group , receiving a placebo supplement . Participants receiving omega-3 fatty acids took 15 × 300 mg capsules per day for 12 weeks . The total daily dose of omega-3 PUFAs was 500 mg docosahexaenoic acid and 1000 mg eicosapentaenoic acid ( EPA ) . The Beck Depression Inventory ® -II ( BDI-II ) was used to assess the severity of depression after treatment . RESULTS After 12 weeks of treatment , BDI-II scores were significantly lower in the placebo and omega-3 group , when compared to their respective baseline scores ( Placebo : t = - 4.6 , p < 0.01 ; Omega-3 : t = - 7.3 , p < 0.01 ) . However , after 12 weeks of treatment , we found no significant difference between both groups with respect to changes in the BDI-II scores ( 0.7 ; 95 % CI , - 0.7 to 2.1 ; p = 0.30 ) . LIMITATIONS This study did not measure blood omega-3 fatty acid concentration and presented a high-dropout rate . Moreover , our results may not be generalizable to other regions . CONCLUSIONS The results show that a combination of omega-3 fatty acids and psychoeducation and psychoeducation alone can contribute to an improvement in symptoms in people with mild to moderate depression . However , there is no difference between the interventions in ameliorating symptoms of depression OBJECTIVES Maternal deficiency of the omega-3 fatty acid , docosahexaenoic acid ( DHA ) , has been associated with perinatal depression , but there is evidence that supplementation with eicosapentaenoic acid ( EPA ) may be more effective than DHA in treating depressive symptoms . This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression . STUDY DESIGN We enrolled 126 pregnant women at risk for depression ( Edinburgh Postnatal Depression Scale score 9 - 19 or a history of depression ) in early pregnancy and r and omly assigned them to receive EPA-rich fish oil ( 1060 mg EPA plus 274 mg DHA ) , DHA-rich fish oil ( 900 mg DHA plus 180 mg EPA ) , or soy oil placebo . Subjects completed the Beck Depression Inventory ( BDI ) and Mini-International Neuropsychiatric Interview at enrollment , 26 - 28 weeks , 34 - 36 weeks , and at 6 - 8 weeks ' postpartum . Serum fatty acids were analyzed at entry and at 34 - 36 weeks ' gestation . RESULTS One hundred eighteen women completed the trial . There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation . The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively . Serum DHA- concentrations at 34 - 36 weeks were inversely related to BDI scores in late pregnancy . CONCLUSION EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum BACKGROUND Current underst and ing of the etiology of autism is based on the interaction of multiple genes with each other and with environmental factors , leading to a neurodevelopmental process that results in the expression of autism spectrum disorder ( ASD ) in the child . This suggests that it might be possible to strengthen resilience to environmental stressors during the perinatal period to improve outcomes and possibly prevent the development of ASD . METHODS We search ed the MEDLINE data base for multiple perinatal factors associated with the development of ASD published between January 1 , 2005 and July 1 , 2018 . The search terms used were " autism " crossed with either " perinatal , " " prenatal , " " gestational , " or " pregnancy , " and crossed again with each perinatal risk factor highlighted in this review including topics on parental health , infections , medications , and environmental stressors . We then search ed interventions that may improve neurodevelopmental outcome before and during pregnancy , including supplements , breastfeeding , and postpartum stress reduction . We identified recent or unique metanalyses and systematic review s of the identified focus and on r and omized controlled trials and summarized these using the most recent and comprehensive review s. RESULTS Folate , omega-3 , vitamin D3 , environmental toxin avoidance , correcting deficiencies , immune boosting , and prolonged breast feeding are all reported to be linked to the possible reduction of adverse pregnancy outcomes including ASD . CONCLUSIONS Studies of individual components for improving pregnancy outcomes and several uncontrolled preconception to infancy medical practice s suggest that multiple interventions might improve the outcomes of pregnancies where there is risk for developing ASD OBJECTIVE Despite treatment advances in other domains , inpatient psychiatric hospitalization rates for individuals with first-episode psychosis remain high . Even with early intervention services , a third or more of individuals are hospitalized over the first 2 years of treatment . Reducing hospitalization is desirable from the individual 's perspective and for public health reasons because hospitalization costs are a major component of treatment costs . METHODS Univariate and multivariate baseline and time-varying covariate analyses were conducted to identify predictors of hospitalization in the Recovery After an Initial Schizophrenia Episode-Early Treatment Program ( RAISE-ETP ) study , a 2-year cluster r and omized trial for participants experiencing a first episode of psychosis who were out patients at study entry . The trial compared an early intervention treatment model ( NAVIGATE ) with usual community care at 34 clinics across the United States . RESULTS RAISE-ETP enrolled 404 participants of whom 382 had one or more postbaseline assessment s that included hospitalization data . Thirty-four percent of NAVIGATE and 37 % of usual-care participants were hospitalized during the trial . Risk analyses revealed significant predictors of hospitalization to be the number of hospitalizations before study entry ; duration of untreated psychosis ; and time-varying days of substance misuse , presence of positive symptoms , and beliefs about the value of medication . CONCLUSIONS These results indicate that hospital use may be decreased by reducing the duration of untreated psychosis and prior hospitalizations , minimizing residual symptoms , preventing substance misuse , and facilitating adherence to medication taking . Addressing these factors could enhance the impact of first-episode early intervention treatment models and also enhance outcomes of people with first-episode psychosis treated using other models Objective : To compare therapeutic effects of eicosapentaenoic acid ( EPA ) , fluoxetine and a combination of them in major depression . Method : Sixty out patients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score ≥15 in the 17-item Hamilton Depression Rating Scale ( HDRS )  were r and omly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine , or their combination for 8 weeks . Double dummy technique was used to double blind the study . Patients were assessed at 2 week intervals . Change in HDRS was the primary outcome measure . Results : Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study , with the last observation carried forward . Treatment , age of onset and baseline HDRS had a significant effect on HDRS at week 8 . EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment . Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms . Response rates ( ≥50 % decrease in baseline HDRS ) were 50 % , 56 % and 81 % in the fluoxetine , EPA and combination groups , respectively . Conclusions : In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder . EPA + fluoxetine combination was superior to either of them alone Short-term clinical trials of omega-3 polyunsaturated fatty acids ( n-3 PUFA ) as add-on therapy in patients with schizophrenia revealed mixed results . The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid . A r and omized placebo-controlled trial was design ed to compare the efficacy of 26-week intervention , composed of either 2.2 g/day of n-3 PUFA , or olive oil placebo , with regard to symptom severity in first-episode schizophrenia patients . Seventy-one patients ( aged 16 - 35 ) were enrolled in the study and r and omly assigned to the study arms . The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale ( PANSS ) . Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA ( p = 0.016 ; effect size ( ES ) = 0.29 ) . A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group ( 69.4 vs 40.0 % ; p = 0.017 ) . N-3 PUFA intervention was also associated with an improvement in general psychopathology , measured by means of PANSS ( p = 0.009 ; ES = 0.32 ) , depressive symptoms ( p = 0.006 ; ES = 0.34 ) , the level of functioning ( p = 0.01 ; ES = 0.31 ) and clinical global impression ( p = 0.046 ; ES = 0.29 ) . The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients Intervention studies of n-3 polyunsaturated fatty acids ( n-3 PUFA ) as add-on therapy in patients with schizophrenia have not examined changes in oxidative stress . A r and omized placebo-controlled trial of a 26-week intervention composed of 2.2g/day of n-3 PUFA was found to reduce symptom severity in first-episode schizophrenia patients . The present study is an extension of our previous report , whose secondary aim was to assess the association between the clinical effect of n-3 PUFA and changes in oxidative stress indices . Seventy-one patients aged 16 - 35 were enrolled in the study and r and omly assigned to the study arms . Total plasma antioxidant capacity and 8-epi-isoprostane F2α content were assessed at baseline and at weeks 8 and 26 of the study as secondary outcome measures . Significant changes in oxidative stress indices favouring the intervention group were observed : decreases in 8-isoprostane F2α ( p<0.001 ) and increases in total plasma antioxidant capacity ( p<0.001 ) . Significant correlations between changes in clinical scores relevant to symptom severity and changes in oxidative indices were observed . The results of the present study hence suggest that the efficacy of a six-month intervention with n-3 PUFA observed in first-episode schizophrenia may be related to improvement in oxidative stress indices & NA ; Schizophrenia is associated with shortening of the lifespan mainly due to cardiovascular events , cancer and chronic obstructive pulmonary disease . Both telomere attrition and decrease of telomerase levels were observed in schizophrenia .  Polyunsaturated fatty acids ( PUFA ) influence multiple biochemical mechanisms which are postulated to accelerate telomere shortening and limit the longevity of patients with schizophrenia . Intervention studies based on add‐on therapy with n‐3 polyunsaturated fatty acids ( n‐3 PUFA ) in patients with schizophrenia did not assess the changes in telomerase levels . A r and omized placebo‐controlled trial named OFFER was design ed to compare the efficacy of a 26‐week intervention composed of either 2.2 g/day of n‐3 PUFA or olive oil placebo with regard to symptom severity in first‐episode schizophrenia patients . The secondary outcome measure of the study was to describe the association between the clinical effect of n‐3 PUFA and changes in telomerase levels . Seventy‐one patients aged 16–35 were enrolled in the study and r and omly assigned to the study arms . The Positive and Negative Syndrome Scale ( PANSS ) was used to assess the change in symptom severity . Telomerase levels of peripheral blood mononuclear cells ( P BMC ) were assessed at three points : at baseline and at weeks 8 and 26 of the intervention . A significantly greater increase in P BMC telomerase levels in the intervention group compared to placebo was observed ( p < 0.001 ) . Changes in telomerase levels significantly and inversely correlated with improvement in depressive symptoms and severity of the illness . The efficacy of a six‐month intervention with n‐3 PUFA observed in first‐episode schizophrenia may be related to an increase in telomerase levels . HighlightsTelomerase level ( TA ) of P BMC s increased during n‐3 PUFA supplementation added to antipsychotics . Significant increase of P BMC s TA was also observed in patients treated with antipsychotics and placebo  . After 26 weeks , the change in TA was significantly higher in the n‐3 PUFA group than in the  placebo group . Changes in TA correlated significantly with changes in depressive symptoms and disease severity We used magnetic resonance imaging to examine the effect of ethyl-eicosapentaenoic acid ( E-EPA ) on hippocampal T(2 ) relaxation time in first episode psychosis patients at baseline and after 12 weeks of follow-up . There was an increase in T(2 ) in the placebo group but not in the E-EPA group , suggesting a neuroprotective effect of E-EPA treatment . In addition , the smaller the increase in T(2 ) , the greater the improvement in negative symptoms
In the central nervous system omega-3 fatty acids modulate cell signaling and affect dopaminergic and serotonergic pathways .
On this basis , a new application for omega-3 fatty acids has been proposed , concerning the treatment of several psychiatric disorders .
The present article is an up date of a previous systematic review and is aim ed to provide a complete report of data published in the period between 1980 and 2019 on efficacy and tolerability of omega-3 fatty acids in psychiatric disorders .