Stress Hormones Cortisol and Aldosterone, and Selected Markers of Oxidative Stress in Response to Long-Term Supplementation with Omega-3 Fatty Acids in Adolescent Children with Depression.

Late childhood and adolescence are crucial periods of brain development with high vulnerability to environmental insults. The aim of this study was to test the hypotheses that in adolescents with depression (a) 12 weeks-supplementation with omega-3 fatty acids results in the attenuation of salivary stress hormone concentrations; (b) the mentioned supplementation improves potentially disrupted daily rhythm of stress hormones; (c) stress hormone concentrations correlate with values of selected markers of oxidative stress. The sample consisted of 60 patients suffering from depression aged 11-18 years. Hormone concentrations in saliva were measured in the morning and midday before (baseline) and after (6, 12 weeks) food supplementation with omega-3 or omega-6 (as comparator) fatty acids. Morning cortisol decreased in response to omega-3 but not omega-6 fatty acids at 12 weeks compared to baseline. No changes were observed in aldosterone concentrations. The obtained results show that adolescent children with depression preserved the daily rhythm of both stress hormones. Baseline morning cortisol concentrations correlated positively with depression severity and lipoperoxides, and negatively with docosahexaenoic acid. Aldosterone concentrations correlated positively with 8-isoprostane. Thus, both hormones showed positive correlation with the selected markers of oxidative stress suggesting that enhanced stress hormone secretion may be associated with increased oxidative tissue damage in adolescent children with depression. This study was registered with the ISRCTN registry (DEPOXIN study, ISRCTN81655012).

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance.

BACKGROUND: Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides. METHODS: The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically. RESULTS: OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3-7 and HDL8-10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals. CONCLUSION: The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

Oxidative Stress Markers and Antioxidant Enzymes in Children and Adolescents with Depressive Disorder and Impact of Omega-3 Fatty Acids in Randomised Clinical Trial.

Oxidative stress (OS) is thought to play a role in mental disorders. However, it is not clear whether the OS is the cause or consequence of the disorder. We investigated markers of oxidative stress (8-isoprostane (8-IsoP-U), lipoperoxides (LP), advanced oxidation protein products (AOPP) and nitrotyrosine (NT)) and antioxidant protection (Trolox equivalent antioxidant capacity (TEAC), activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in 60 paediatric and adolescent patients with depressive disorder (DD) compared to healthy controls. The patients were divided into two groups (1:1). One group received an emulsion of omega-3 fatty acid (FA), and the other group an emulsion of sunflower oil with omega-6 FA for 12 weeks. The levels of 8-IsoP-U, AOPP and NT were increased, and GPx activity was decreased in patients compared to the controls. We found a significant positive correlation of the Children's Depression Inventory score with NT and a negative correlation with TEAC, SOD and GPx. NT correlated positively with the baseline omega-6/omega-3 FA ratio and a negatively with SOD. A supplementation with omega-3 FA, but not with omega-6 FA, decreased 8-IsoP-U, AOPP, NT levels and increased TEAC and SOD activity. Our results suggest that NT may play a role in the pathophysiology of DD, while elevated isoprostane is likely caused by the high omega-6/omega-3 FA ratio. Omega-3 FA supplementation reduces oxidative stress in patients with DD. This study was registered with the ISRCTN registry (ISRCTN81655012).

The Effect of Omega-3 Fatty Acids on Thromboxane, Brain-Derived Neurotrophic Factor, Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial.

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child's Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).

Lipid Profile, Lipoprotein Subfractions, and Fluidity of Membranes in Children and Adolescents with Depressive Disorder: Effect of Omega-3 Fatty Acids in a Double-Blind Randomized Controlled Study.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids such as total cholesterol (TCH), LDL-, and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. The primary endpoint of the study was the effect of omega-3 FA on the severity of depression in children and adolescents. This study aimed to investigate the secondary endpoint, relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities, and erythrocyte membrane fluidity in 58 depressed children and adolescents (calculated by the statistical program on the effect size), as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, and LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. Improvement of symptoms in the group supplemented with a fish oil emulsion rich in omega-3 FA in contrast to omega-6 FA (emulsion of sunflower oil) has been observed. We are the first to report that omega-3 FAs, but not omega-6 FA, increase large HDL subfractions (anti-atherogenic) after 12 weeks of supplementation and decrease small HDL subfractions (proatherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and the large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder. The study was registered under ISRCTN81655012.

Omega-3 fatty-acids modulate symptoms of depressive disorder, serum levels of omega-3 fatty acids and omega-6/omega-3 ratio in children. A randomized, double-blind and controlled trial.

Omega-3 fatty acids (FA) are a promising adjuvant therapy for depressive disorder (DD) in adults. The objective of this single-centre, randomized, double-blind and controlled study was to compare the efficacy of an omega-3 FA fish oil emulsion with a control oil emulsion alongside the standard treatment for depression in children and adolescents suffering from DD or mixed anxiety depressive disorder (MADD) and to analyse serum fatty acid levels and omega-6/omega-3 FA ratio before and after the intervention. 60 children were randomised 1:1 to the intervention (Om3) or active comparator (Om6) groups. Children's Depression Inventory (CDI) ratings were performed at the baseline, every 2 weeks for a 12-week intervention period. Significant reductions in CDI scores were observed after 6 and 12 weeks of intervention in the Om3 group and in the DD subgroup compared to the Om6 and MADD subgroup. Ratio of omega-6/omega-3 decreased in Om3 but not in Om6 from 24.2/1 to 7.6/1 after 6 weeks, EPA, omega-6/omega-3 ratio, but not DHA, correlated with severity symptoms at the baseline. An omega-3 fatty acid rich fish oil emulsion may be an effective adjuvant supplement during the treatment of depressive disorders in children. Trial registration: ISRCTN 81655012.