Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial.

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Roles of Omega-3 Polyunsaturated Fatty Acids in Managing Cognitive Impairment in Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease (COPD) contributes significantly to the death of people worldwide, especially the elderly. An essential feature of COPD is pulmonary inflammation, which results from long-term exposure to noxious substances from cigarette smoking and other environmental pollutants. Pulmonary inflammatory mediators spill over to the blood, leading to systemic inflammation, which is believed to play a significant role in the onset of a host of comorbidities associated with COPD. A substantial comorbidity of concern in COPD patients that is often overlooked in COPD management is cognitive impairment. The exact pathophysiology of cognitive impairment in COPD patients remains a mystery; however, hypoxia, oxidative stress, systemic inflammation, and cerebral manifestations of these conditions are believed to play crucial roles. Furthermore, the use of medications to treat cognitive impairment symptomatology in COPD patients has been reported to be associated with life-threatening adverse effects, hence the need for alternative medications with reduced side effects. In this Review, we aim to discuss the impact of cognitive impairment in COPD management and the potential mechanisms associated with increased risk of cognitive impairment in COPD patients. The promising roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in improving cognitive deficits in COPD patients are also discussed. Interestingly, ω-3 PUFAs can potentially enhance the cognitive impairment symptomatology associated with COPD because they can modulate inflammatory processes, activate the antioxidant defence system, and promote amyloid-beta clearance from the brain. Thus, clinical studies are crucial to assess the efficacy of ω-3 PUFAs in managing cognitive impairment in COPD patients.

Omega-3 Polyunsaturated Fatty Acids for Core Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials.

Objective: Previous studies have shown conflicting results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs) in improving attention-deficit/hyperactivity disorder (ADHD) symptoms. This inconsistency may be due to differences in dosage, composition, and treatment duration. The current meta-analysis aims to address this inconsistency by improving subtype analyses and focusing on heterogeneity in treatment duration, omega-3 PUFA composition, and eicosapentaenoic acid (EPA) dose.Data Sources and Study Selection: We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for randomized controlled trials of omega-3 PUFAs for ADHD, without publication year or language limitations, up to November 27, 2022. The primary outcome was the improvement of ADHD core symptoms. Subgroup analyses were conducted based on the formula, dosages, and composition ratios of omega-3 PUFAs. To ensure methodological quality, the Cochrane Risk-of-Bias Tool 1.0 was utilized to assess the risk of bias for each study included in the analysis. The pooled data were then analyzed using the random-effect meta-analysis, and the inverse variance method was employed.Data Extraction: The outcomes of interest were extracted using a data extraction form developed for this study.Results: Twenty-two studies with 1,789 participants were included in the analysis. Overall, omega-3 PUFAs did not significantly improve ADHD core symptoms compared to placebo (standardized mean difference [SMD]: -0.16; 95% CI, -0.34 to 0.01; P = .07). However, in the subgroup of studies with a treatment duration of at least 4 months, omega-3 PUFAs were significantly more effective than placebo (SMD: -0.35; 95% CI,-0.61 to -0.09; P = .007). Neither high eicosapentaenoic acid (EPA) dosage nor high EPA/docosahexaenoic acid (DHA) ratio was found to improve ADHD symptoms.Conclusions: Our findings indicate that omega-3 PUFAs did not improve ADHD core symptoms, but long-term supplementation may have potential benefits. The main limitation of the study was the moderate heterogeneity and small sample sizes in subgroup analyses and the lack of dietary pattern information.

Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention. This study aimed to provide a meta-analytic and comprehensive review on the adverse effects of all kinds of ω-3 PUFA supplementation reported in randomized controlled trials (RCTs) in human subjects. A systematic review of RCTs published between 1987 and 2023 was carried out based on searches of 8 electronic databases. All RCTs that compared the adverse effects of ω-3 PUFAs containing eicosapentaenoic acid, docosahexaenoic acid, or both compared with controls (a placebo or a standard treatment) were included. The primary outcome was the adverse effects related to ω-3 PUFA prescription. A total of 90 RCTs showed that the ω-3 PUFA group, when compared with the placebo, had significantly higher odds of occurrence of diarrhea (odds ratio [OR] = 1.257, P = 0.010), dysgeusia (OR = 3.478, P < 0.001), and bleeding tendency (OR = 1.260, P = 0.025) but lower rates of back pain (OR = 0.727, P < 0.001). The subgroup analysis showed that the prescription ω-3 PUFA products (RxOME3FAs) had higher ω-3 PUFA dosages than generic ω-3 PUFAs (OME3FAs) (3056.38 ± 1113.28 mg/d compared with 2315.92 ± 1725.61 mg/d), and studies on RxOME3FAs performed more standard assessments than OME3FAs on adverse effects (63% compared with 36%). There was no report of definite ω-3 PUFA-related serious adverse events. The subjects taking ω-3 PUFAs were at higher odds of experiencing adverse effects; hence, comprehensive assessments of the adverse effects may help to detect minor/subtle adverse effects associated with ω-3 PUFAs. This study was registered at PROSPERO as CRD42023401169.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), somatic and fatigue symptoms in cardiovascular diseases comorbid major depressive disorder (MDD): A randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVDs) and major depressive disorder (MDD) are the two most disabling diseases. Patients with CVDs comorbid depression had somatic and fatigue symptoms and were associated with chronic inflammation and omega-3 polyunsaturated fatty acid (n-3 PUFA) deficits. However, there have been limited studies on the effects of n-3 PUFAs on somatic and fatigue symptoms in patients with CVDs comorbid MDD. METHOD: Forty patients with CVDs comorbid MDD (58% males, mean age of 60 ± 9 years) were enrolled and randomised to receive either n-3 PUFAs (2 g of eicosapentaenoic acid [EPA] and 1 g of docosahexaenoic acid[DHA] per day) or placebo in a 12-week double-blind clinical trial. We assessed the somatic symptoms with Neurotoxicity Rating Scale (NRS) and fatigue symptoms with Fatigue Scale at baseline, weeks 1, 2, 4, 8 and 12, as well as blood levels of Brain-Derived Neurotrophic Factor (BDNF), inflammatory biomarkers and PUFAs, at the baseline and week 12. RESULTS: The n-3 PUFAs group had a greater reduction in Fatigue scores than the placebo group at Week 4 (p =.042), while there were no differences in the changes of NRS scores. N-3 PUFAs group also had a greater increase in EPA (p =.001) and a greater decrease in total n-6 PUFAs (p =.030). Moreover, in the subgroup analyses in the younger age group (age < 55), the n-3 PUFAs group had a greater reduction on NRS total scores at Week 12 (p =.012) and NRS Somatic scores at Week 2 (p =.010), Week 8 (p =.027), Week 12 (p =.012) than the placebo group. In addition, the pre- and post-treatment changes of EPA and total n-3 PUFAs levels were negatively associated with the changes of NRS scores at Weeks 2, 4, and 8 (all p <.05), and the changes of BDNF levels were negatively associated with NRS scores at Weeks 8 and 12 (both p <.05) in the younger age group. In the older age group (age ≥ 55), there were a lesser reduction on NRS scores at Weeks 1, 2 and 4 (all p <.05), but a greater reduction on Fatigue score at Week 4 (p =.026), compared to the placebo group. There was no significant correlation between the changes of blood BDNF, inflammation, PUFAs and NRS and Fatigue scores in general and in the older age group. CONCLUSION: Overall, n-3 PUFAs improved the fatigue symptoms in patients with CVDs comorbid MDD and the general somatic symptoms in specific subpopulation of younger age patients, and perhaps via the interplay between BDNF and EPA. Our findings provide promising rationales for future studies to investigate the treatment effects of omega-3 fatty acids on fatigue and somatic symptoms of chronic mental and medical diseases.

Psychological Outcomes and Quality of Life of Fibromyalgia Patients with Vitamin D Supplementation-A Meta-Analysis.

The efficacy of current pharmaceutical treatments for fibromyalgia are limited. Vitamin D has shown promise in relieving pain. However, there is a lack of comprehensive analysis of psychological outcomes with vitamin D supplementation in fibromyalgia. This study aimed to investigate the impact of vitamin D supplementation on psychological outcomes and quality of life in fibromyalgia patients, given the unmet clinical need for effective treatment options. A meta-analysis of randomized controlled trials comparing vitamin D to placebo and prospective studies examining changes before and after vitamin D supplementation for patients with fibromyalgia was conducted to evaluate the effects of vitamin D on psychological outcomes, quality of life, and pain scores in patients with fibromyalgia. Databases were searched for relevant articles published from earliest available date to October 31, 2022. (PROSPERO number, CRD42022369889). We included 8 trials with a total of 694 participants and found that vitamin D supplementation had significant positive effects on physical function (standard mean differences (SMD) = 0.44, 95% CI = [0.10, 0.77 ]), role limitations due to emotional health (SMD = 0.57, 95% CI = [0.32, 0.82]), social function (SMD = 0.50, 95% CI = [0.08, 0.93]), and general health (SMD = 0.36, 95% CI = [0.11, 0.61]). Improvement of the Fibromyalgia Impact Questionnaire (FIQ) scores was noted (SMD = -0.414, 95% CI = [-0.808, -0.021]), but not on the Visual Analog Scale (VAS) (SMD = -0.15, 95% CI = [-0.771, 0.471]) and the Beck's Depression Inventory (BDI) scores (SMD = -0.456, 95% CI = [-1.27, 0.30]). In conclusion, vitamin D supplementation might be an alternative option for improvement of psychological outcomes and quality of life in patients with fibromyalgia.

Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials.

The role of omega-3 polyunsaturated fatty acids (PUFAs) in primary and secondary prevention on major cardiovascular events (MCE) is inconclusive due to the potential heterogeneity in study designs of formulas, dosages, and ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the findings of previous randomized controlled trials (RCTs). Here we conducted a comprehensive narrative review of pre-clinical studies and updated a network meta-analysis (NMA) to determine the comparative efficacy against MCE with different EPA/DHA dosages and formulas. We found that pure EPA was ranked the best option in the secondary prevention (hazard ratio: 0.72, 95% confidence interval: 0.65 to 0.81) from the NMA of 39 RCTs with 88,359 participants. There was no evidence of omega-3 PUFAs' efficacy in primary prevention. The mechanisms of omega-3 PUFAs' cardiovascular protection might link to the effects of anti-inflammation and stabilization of endothelial function from PUFA's derivatives including eicosanoids and the special pre-resolving mediators (SPMs).

Omega-3 fatty acids in the psychological and physiological resilience against COVID-19.

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.

Nutritional Neuroscience as Mainstream of Psychiatry: The Evidence- Based Treatment Guidelines for Using Omega-3 Fatty Acids as a New Treatment for Psychiatric Disorders in Children and Adolescents.

Omega-3 polyunsaturated fatty acids (or omega-3 PUFAs, n-3 PUFAs) are essential nutrients throughout the life span. Recent studies have shown the importance of n-3 PUFAs supplementation during prenatal and perinatal period as a potential protective factor of neurodevelopmental disorders. N-3 PUFAs have been reported to be lower in youth with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD). N-3 PUFAs supplementation has shown potential effects in the improvement of clinical symptoms in youth with ADHD, ASD, and MDD, especially those with high inflammation or a low baseline n-3 index. Moreover, it has been suggested that n-3 PUFAs had positive effects on lethargy and hyperactivity symptoms in ASD. For clinical application, the following dosage and duration are recommended in youth according to available randomized controlled trials and systemic literature review: (1) ADHD: a combination of eicosapentaenoic acid (EPA) ＋ docosahexaenoic acid (DHA) ≥ 750 mg/d, and a higher dose of EPA (1,200 mg/d) for those with inflammation or allergic diseases for duration of 16-24 weeks; (2) MDD: a combination of a EPA ＋ DHA of 1,000-2,000 mg/d, with EPA:DHA ratio of 2 to 1, for 12-16 weeks; (3) ASD: a combination of EPA ＋ DHA of 1,300-1,500 mg/d for 16-24 weeks as add-on therapy to target lethargy and hyperactivity symptoms. The current review also suggested that n-3 index and inflammation may be potential treatment response markers for youth, especially in ADHD and MDD, receiving n-3 PUFA.

Plasma estradiol levels and antidepressant effects of omega-3 fatty acids in pregnant women.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) reduce depressive symptoms through an anti-inflammatory effect, and injection of both omega-3 PUFAs and estradiol (E2) induces antidepressant-like effects in rats by regulating the expression of inflammatory cytokines. The aims of this study were to examine the association of increased E2 during pregnancy with depressive symptoms and with inflammatory cytokines in women who were and were not supplemented with omega-3 PUFAs. METHODS: Pregnant women with Edinburgh Postnatal Depression Scale scores ≥9 were recruited at 12-24 weeks of gestation. The participants were randomly assigned to receive 1800 mg omega-3 fatty acids (containing 1206 mg eicosapentaenoic acid [EPA]) or placebo for 12 weeks. E2, omega-3 PUFAs, high-sensitivity C-reactive protein, interleukin-6, and adiponectin were measured at baseline and at the 12-week follow-up. Multivariable regression analyses were conducted to examine the association of the changes of E2 and omega-3 PUFAs with the changes in depressive symptoms and with the changes of inflammatory cytokines at follow-up by intervention group. RESULTS: Of the 108 participants in the trial, 100 (92.6%) completed the follow-up assessment including blood sampling. Multivariable regression analyses revealed that the increase of EPA and E2 was significantly associated with a decrease in depressive symptoms among the participants assigned to the omega-3 group, but not among those assigned to the placebo group. Neither E2 nor any PUFAs were associated with a change in inflammatory cytokines. CONCLUSION: Supplementation with EPA and increased levels of E2 during pregnancy might function together to alleviate antenatal depression through a mechanism other than anti-inflammation.

Omega-3 polyunsaturated fatty acids in cardiovascular diseases comorbid major depressive disorder - Results from a randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVDs) and major depressive disorder (MDD) will be the two most disabling diseases by 2030. Patients with CVDs comorbid depression had lower levels of total omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), and a higher omega-6 to omega-3 ratio. However, there have been limited studies on the effects n-3 PUFAs on MDD in patients with CVDs. METHOD: We have enrolled a total of 59 patients (64% males, mean age of 61.5 ±â€¯9.0 years and mean education of 10.2 ±â€¯4.2 years) with CVDs comorbid MDD. They were randomized into either receiving n-3 PUFAs (2 g per day of eicosapentaenoic acid (EPA) and 1 g of DHA) or placebo for 12 weeks. We assessed depression symptom severity with Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI), as well as blood fatty acid levels, electrocardiogram and blood biochemistry, at the baseline and at the endpoint. RESULTS: There were no differences between the n-3 PUFAs and placebo group in the changes of HAMD and BDI total scores, while PUFAs group had a greater reduction in HAMD Cognition subscale scores than the placebo group at week 8 (p < 0.05). Moreover, subgroup analyses found that the n-3 group had a greater reduction of HAMD Core subscale scores than the placebo group at the end of week 12 (p < 0.05) for the very severe DEP group (HAMD ≥ 23). CONCLUSION: Overall, n-3 PUFAs did not show a beneficial effect on depressive symptoms when compared with placebo. However, when stratified with depression severity, n-3 PUFAs supplementation improved core depression symptoms in the very severe MDD group. N-3 PUFAs supplementation may provide a treatment option for a subpopulation of patients with CVDs comorbid MDD.

High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels.

No studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6-18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.

Differences between Japan and Taiwan in the treatment of pregnant women with depressive symptoms by omega-3 fatty acids: An open-label pilot study.

OBJECTIVES: Although safe approaches for improving depression in pregnancy are required and the efficacy of omega-3 polyunsaturated fatty acids (PUFAs) has been suggested, the amount of supplemental omega-3 PUFAs has varied among previous studies and adequate amount might be different among countries. The aim of this pilot study is to explore the feasibility of using 1800 mg of omega-3 PUFAs supplementation for our future double-blind, placebo-control trial, and to clarify the clinical difference and the similarity between two sites of Japan and Taiwan. METHODS: Pregnant women between 12 and 24 weeks' gestation with depressive symptoms were recruited. Participants were supplemented daily with omega-3 PUFAs capsules containing 1206 mg eicosapentaenoic acid and 609 mg docosahexaenoic acid for 12 weeks. The primary outcome was change in total score on the 17-item Hamilton Rating Scale for Depression (HAMD) at 12 weeks after supplementation. RESULTS: Eight pregnant women in Japan and five in Taiwan participated in the study. A substantial proportion of pregnant women reported high consumption of omega-3 supplements and dietary fish were excluded in Taiwan rather than in Japan sites. The decrease in HAMD score from baseline to 12 weeks after the start of the intervention was significantly larger in Japanese participants than in Taiwanese participants (Wilcoxon rank sum test; P = 0.045). DISCUSSION: The improvement of depressive symptoms was smaller at the Taiwan site than at the Japan site. Differences in psychopathology of recruited participants identified by self-rating scales might affect the degree of population heterogeneity and the treatment efficacy. A randomized-controlled trial is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01948596.

Safety and tolerability of prescription omega-3 fatty acids: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, prescription omega-3 fatty acid products (RxOME3FAs) have been approved for medical indications. Nonetheless, there is no comprehensive analysis of safety and tolerability of RxOME3FAs so far. METHODS: A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FA products were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity. RESULTS: Among the 21 included RCTs (total 24,460 participants; 12,750 from RxOME3FA treatment cohort and 11,710 from control cohort), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (fishy taste; p = 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements [elevated fasting blood sugar (p = 0.005); elevated alanine transaminase (p = 0.022); elevated blood urea nitrogen (p = 0.047); decreased hemoglobin (p = 0.002); decreased hematocrit (p = 0.009)]. Subgroup analysis revealed that EPA/DHA combination products were associated with more treatment-related gastrointestinal adverse events [eructation (belching; p = 0.010); nausea (p = 0.044)] and low-density lipoprotein cholesterol elevation (p = 0.009; difference in means = 4.106mg/dL). CONCLUSION: RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs.

Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder: a Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies.

The role of omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) in the pathogenesis and treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD) is unclear. A systematic review followed by meta-analysis was conducted on: (1) randomized controlled trials (RCTs) assessing the effects of n-3 PUFAs on clinical symptoms and cognition in children and adolescent with ADHD; and (2) case-control studies assessing the levels of n-3 PUFAs in blood and buccal tissues of children and adolescents with ADHD. In seven RCTs, totalling n=534 randomized youth with ADHD, n-3 PUFAs supplementation improves ADHD clinical symptom scores (g=0.38, p<0.0001); and in three RCTs, totalling n=214 randomized youth with ADHD, n-3 PUFAs supplementation improves cognitive measures associated with attention (g=1.09, p=0.001). Moreover, children and adolescents with ADHD have lower levels of DHA (seven studies, n=412, g=-0.76, p=0.0002), EPA (seven studies, n=468, g=-0.38, p=0.0008), and total n-3 PUFAs (six studies, n=396, g=-0.58, p=0.0001). In summary, there is evidence that n-3 PUFAs supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD, and that these youth have a deficiency in n-3 PUFAs levels. Our findings provide further support to the rationale for using n-3 PUFAs as a treatment option for ADHD.

Polyunsaturated fatty acids and inflammatory markers in major depressive episodes during pregnancy.

INTRODUCTION: Prenatal depression (PND) is a common psychiatric disorder in pregnant women and leads to psychosocial dysfunction, high suicidal rate, and adverse childcare. Patients with PND have omega-3 polyunsaturated fatty acid (omega-3 or n-3 PUFAs) deficits, which might link to chronic low-grade inflammatory process and the pathophysiological mechanisms of depression. In this case-control study, we examined the levels of PUFAs and inflammatory cytokines in PND. METHOD: Blood samples were obtained and analyzed from 16 healthy controls and 17 depressed cases (PND group) diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Independent sample t-test and correlation analysis were performed with Statistical Package for the Social Sciences (SPSS) logistics correlation analysis. RESULTS: PND group had significantly lower levels of total n-3 (p=0.026), docosahexaenoic acid (DHA) (p=0.020) and eicosapentaenoic (EPA) (p=0.019) but a higher omega-6 (n-6)/n-3 PUFAs ratio (p=0.007) and tumor necrosis factor alpha (TNF-α) (p=0.016) level. Moreover, the duration of current PND episodes were also significantly correlated with DHA, EPA, n-3 PUFAs, n-6/n-3 ratio and TNF-α. In terms of PUFAs and cytokine levels, only DHA was inversely correlated with TNF-α. CONCLUSION: PND is significantly associated with lower DHA, EPA, and total n-3 PUFAs levels and an increased n-6/n-3 PUFAs ratio, while the duration of PND is associated with lower levels of n-3 PUFAs, including DHA and EPA. The correlation of PUFAs levels with depression and TNF-α level grant further investigation into the inflammatory process underlying PND, mediated by PUFAs.

Polyunsaturated fatty acids levels and initial presentation of somatic symptoms induced by interferon-alpha therapy in patients with chronic hepatitis C viral infection.

OBJECTIVES: Somatic symptoms are common in depressive disorder and are similar to sickness behaviors due to inflammatory activation after cytokine administration. Omega-3 polyunsaturated fatty acids (PUFAs) are natural anti-inflammatory agents and may reduce inflammation-induced behavioral changes. The aim of this study was to investigate the role of PUFAs on the development of somatic symptoms and depression in patients of hepatitis C virus infection (HCV) receiving interferon-alpha therapy (IFN-α) in a prospective manner. METHODS: In this 24-week, prospective cohort study, 43 patients with chronic HCV ongoing IFN-α therapy were assessed with the mini-international neuropsychiatric interview for major depressive episodes and neurotoxicity rating scale (NRS) for somatic symptoms. RESULTS: One-third later developed IFN-α-induced depression (depression (DEP) group). As compared to subjects without depression, DEP group had higher NRS scores (P < 0.001), lower eicosapentaenoic acid (EPA) levels (P = 0.038) at week 2. Somatic symptoms, regardless of painful/non-painful characteristics, had positive association with arachidonic acid (P < 0.05), and negative association with EPA (P < 0.05). CONCLUSION: This study implies that early intervention with omega-3 PUFAs might be a promising strategy to prevent depression and somatic symptoms in patients receiving cytokine therapy.

Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial.

BACKGROUND: Interferon (IFN)-α therapy for chronic hepatitis C virus infection is frequently associated with depression. The routine prophylaxis with antidepressants might expose patients to adverse effects, hence, the need for alternative preventive interventions. Omega-3 polyunsaturated fatty acids are safe and effective essential nutritional compounds used for the treatment of depression, putatively through an anti-inflammatory action. In addition, lower erythrocyte levels of omega-3 polyunsaturated fatty acids have been associated with an increased risk of IFN-induced depression. METHODS: We conducted a 2-week, double-blind, placebo-controlled trial comparing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and placebo for the prevention of IFN-α-induced depression. A total of 162 patients consented to participate and were randomized to the study. All of the patients completed the 2-week trial; 152 participants were followed throughout the 24 weeks of IFN-α treatment and were included in the analysis. RESULTS: Compared with placebo, the incident rates of IFN-α-induced depression were significantly lower in EPA-treated but not in DHA-treated patients (10% and 28%, respectively, versus 30% for placebo, p = .037). Both EPA and DHA significantly delayed the onset of IFN-induced depression (week of onset: 12.0 and 11.7, respectively, versus 5.3 for placebo, p = .002). EPA and DHA were both well tolerated in this population. EPA treatment increased both EPA and DHA erythrocyte levels, but DHA only increased DHA erythrocyte levels. CONCLUSIONS: EPA is effective in the prevention of depression in hepatitis C virus patients received IFN-α therapy. Our study confirms the notion that anti-inflammatory strategies are effective antidepressants in the context of depression associated with inflammation.