Exploring the association between whole blood Omega-3 Index, DHA, EPA, DHA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education

European Journal of Nutrition, Mar 2018

I. S. M. van der Wurff, C. von Schacky, T. Bergeland, R. Leontjevas, M. P. Zeegers, P. A. Kirschner, R. H. M. de Groot

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:


Exploring the association between whole blood Omega-3 Index, DHA, EPA, DHA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education

European Journal of Nutrition https://doi.org/10.1007/s00394 Exploring the association between whole blood Omega-3 Index, DHA, EPA, DHA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education I. S. M. van der Wurff 0 1 2 4 5 6 7 C. von Schacky 0 1 2 4 5 6 7 T. Bergeland 0 1 2 4 5 6 7 R. Leontjevas 0 1 2 4 5 6 7 M. P. Zeegers 0 1 2 4 5 6 7 P. A. Kirschner 0 1 2 4 5 6 7 R. H. M. de Groot 0 1 2 4 5 6 7 0 Omegametrix , 82 152 Martinsried , Germany 1 Welten Institute, Research Centre for Learning, Teaching, and Technology, Open University of the Netherlands , Valkenburgerweg 177, P.O. Box 2960, 6419 AT Heerlen , The Netherlands 2 Abbreviations AA Arachidonic acid , 20:4n-6 BF Bayes factor 3 I. S. M. van der Wurff 4 University of Oulu , Oulu , Finland 5 Centre for Epidemiologic Studies Depression scale Dihomo-γ-linolenic acid , C20:3n-6 6 Aker BioMarine Antarctic AS , 1327 Lysaker , Norway 7 Preventive Cardiology, Medical Clinic and Poli-Clinic I, Ludwig Maximilians-University Munich , Munich , Germany Purpose Depression is common in adolescents and long-chain polyunsaturated fatty acids (LCPUFA) are suggested to be associated with depression. However, research in adolescents is limited. Furthermore, self-esteem has never been studied in relation to LCPUFA. The objective here was to determine associations of depression and self-esteem with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), Omega-3 Index (O3I), n-6 docosapentaenoic acid (n-6 DPA, also called Osbond acid, ObA), n-3 docosapentaenoic acid (DPA), and arachidonic acid (AA) concentrations in blood of adolescents attending lower general secondary education (LGSE). Methods Baseline cross-sectional data from a krill oil supplementation trial in adolescents attending LGSE with an O3I ≤ 5% were analysed using regression models built with the BayesFactor package in R. Fatty acids and O3I were determined in blood. Participants filled out the Centre for Epidemiologic Studies Depression (CES-D) scale and the Rosenberg Self-Esteem scale (RSE). Results Scores indicative of depression (CES-D ≥ 16) were found in 29.4% of the respondents. Of all fatty acids, we found extreme evidence [Bayes factor (BF) > 100] for a weak negative association between ObA and depression score [− 0.16; 95% credible interval (CI) − 0.28 to − 0.04; BF10 = 245], and substantial evidence for a weak positive association between ObA and self-esteem score (0.09; 95% CI, − 0.03 to 0.20; BF10 = 4). When all fatty acids were put in one model as predictors of CES-D or RSE, all of the 95% CI contained 0, i.e., no significant association. Conclusion No evidence was found for associations of DHA, EPA and O3I with depression or self-esteem scores in LGSE adolescents with O3I ≤ 5%. The associations of higher ObA status with lower depression and higher self-esteem scores warrant more research. Adolescents; Depressed mood; Long-chain polyunsaturated fatty acid; Self-esteem; Omega-3 Index; Healthy youth; High schoolers; Brain functioning - CES-D DGLA 6 Faculty of Psychology and Educational Sciences, Open University of the Netherlands, 6419 AT Heerlen, The Netherlands Nutrition and Translational Research in Metabolism (School NUTRIM), Maastricht University, 6200 MD Maastricht, The Netherlands Care and Public Health Research Institute (School CAPHRI), Maastricht University, 6200 MD Maastricht, The Netherlands DHA DPA EPA LCPUFA LGSE O3I ObA RSE Docosahexaenoic acid, C22:6n-3 Docosapentaenoic acid, 22:5n-3 Eicosapentaenoic acid, C20:5n-3 Long-chain polyunsaturated fatty acid Lower general secondary education Omega 3-Index Osbond acid, n-6 docosapentaenoic acid, 22:5n-6 Rosenberg Self Esteem Questionnaire Introduction Depression affects approximately 350 million people worldwide and is especially common in adolescence [ 1, 2 ]. It has been suggested that 14–25% of adolescents will experience at least one depressive episode before the age of 18 [3]. Adolescent depression has been associated with many adverse short- and long-term outcomes such as poor social relationships, lower concentration, lower school performance, negative physical and mental health outcome, and increased risk for adult depression [ 4–7 ]. Subthreshold depression (i.e., depressive symptoms are present but criteria for a major depression are not met) is also common, with a life-time prevalence up to age 17 varying between 5.3 and 12% [8]. Subthreshold depression has also been related to poorer quality of life, socio-emotional dysfunction, and increased risk for the development of major depression [ 9, 10 ]. Depression is a complex and heterogeneous disorder and its aetiology is not completely understood. Many factors have been related to the commencement of depression: heritability, childhood adversity, acute stressful live events, and chronic stress among others [ 11–15 ]. Depression can lead to changes in brain structures, production of proinflammatory factors, neuroinflammation, alteration of the immune system, dysfunction and elevation of homocysteine levels, blood flow abnormalities, and a decrease in glucose metabolism [ 16–21 ]. Long-chain polyunsaturated fatty acids (LCPUFA) have been suggested to be associated with depression. LCPUFA are important constituents of all cell membranes and are involved in many aspects of brain functioning such as neuronal membrane fluidity, brain blood flow, signal transduction and neurotransmission [ 22, 23 ]. Moreover, LCPUFA have been suggested to modulate neuroendocrine factors, have anti-inflammatory properties and may in this way help counteract or reduce the neurobiological changes associated with depression [24]. Multiple observational studies have shown that blood and brain eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) concentrations are lower in people with a depression compared to non-depressed controls [ 25–28 ]. Moreover, a number of intervention trials have shown a positive effect of LCPUFA supplementation on depression [ 29–32 ], but not all [ 33, 34 ]. Studies in adolescents either focus on adolescents in treatment for depression [ 35, 36 ], on dietary intake of LCPUFA [ 37, 38 ], or on adolescents and adults together [ 39 ]. There is only one study, to the best of our knowledge, which investigates LCPUFA status and depressive symptoms in adolescents from the general population. Mamalakis et al. showed a negative association between EPA measured in adipose tissue and depression score measured by the Centre for Epidemiologic Studies Depression (CES-D) scale after correction for adiponectin, indicating that a lower EPA status was associated with more depression. Furthermore, they showed a positive association between dihomo-gamma linolenic acid (DGLA, C20:3n-6) in adipose tissue and depression score measured with the Beck Depression Inventory, again after correction for adiponectin, indicating that a lower DGLA status is associated with less depression. Last, depression occurs more often in adults and adolescents with a lower socioeconomic status [ 40, 41 ]. However, the association between the Omega-3 Index (O3I) measured in blood and depression in adolescents with a lower education level has, to our knowledge, not yet been studied. Thus, little is known about the association between omega-3 fatty acids and depression in healthy adolescents of a lower educational level. We investigated the association between the O3I, measured in blood and depression in a sample of second year students of lower general secondary education (LGSE). The O3I is the amount of EPA + DHA expressed as a percentage of total identified fatty acids after response factor correction and a correction for the fact that whole blood was used instead of the normally used erythrocytes. We expected that a higher O3I would be associated with less depressive feelings. Second, associations between DHA, EPA, docosapentaenoic acid (DPA, 22:5n-3), arachidonic acid (AA, 20:4n-6), and Osbond acid (ObA also called n-6 docosapentaenoic acid, 22:5n-6) measured in blood and depression were explored. We focussed on AA, DHA and EPA because they are implicated to play a role in mental health [ 42 ], whereas ObA is considered to be a functional shortage indicator of DHA [ 43 ] and DPA as the major intermediate between DHA and EPA. Therefore, it was expected that higher DHA, EPA and DPA were associated with lower depression scores, and that higher AA and ObA were associated with higher depression scores in adolescents. Furthermore, exploratively, we estimated the associations of the fatty acids with self-esteem. Self-esteem is a core construct of mental health as it represents a person’s overall evaluation of his or her own worth [ 44 ]. Low self-esteem has been associated with poor health behaviour and many forms of mental illness, including an association between low self-esteem and major depression in adolescents [ 44–46 ] and even negative long-term physical and mental health outcomes [ 45, 47 ]. However, to our knowledge, studies are lacking that explore an association between fatty acids and self-esteem. Blood analyses Methods This study used baseline data from a large double-blind, randomised, placebo controlled intervention study (Food2Learn) to study the effect of 1 year of krill oil supplementation on cognitive performance, academic achievement, and mental well-being of students in the second year of LGSE. Full details about the cohort and measurements have been reported previously [ 48 ]. Food2Learn was approved by the Medical Ethical Committee of Atrium-Orbis-Zuyd Hospital Heerlen, the Netherlands (NL45803.096.13). Each participant as well as parent(s) and/or guardian(s) provided written informed consent for participation in the study. Food2Learn is registered at The Netherlands Trial Register (NTR4082) and at Clinicaltrials.gov (NCT02240264). Data collection Students of 17 schools offering LGSE in the Netherlands participated in Food2Learn. In the Netherlands, secondary education is divided into three levels: pre-university, higher general and lower general secondary education (LGSE). Approximately 38% of all adolescents in the Netherlands attend LGSE, which is again subdivided into four levels; for the current study, students from the highest sublevel, the theoretical learning pathway (TLP), were recruited. Approximately 40% of students attending LGSE are in the TLP [ 49 ]. We approached students in the second year of the LGSE-TLP, who are between 13 and 15 years of age. LGSETLP students at participating schools were approached in a classroom setting and the study was explained orally by a research assistant who also used video material to support the presentation. Students then received an information letter and were asked to discuss their participation with their parent(s) and/or guardian(s). If students wanted to participate, they had to hand in an informed consent form signed by both themselves and their parent(s) and/or guardian(s). After informed consent was received the student received a finger prick to determine the O3I. Only students with a low O3I (defined as O3I≤ 5%) could participate in the study as this was a selection criterion of the main Food2Learn study, as it is to be expected that an effect of supplementation is more likely in those with a low baseline O3I. Thus, participants with an O3I > 5% were not included in the study. At baseline, participants filled out a number of questionnaires to determine mood status and self-esteem, and to collect information with respect to a number of covariates. A finger prick was administered by a trained researcher or research assistant with an automated one-time-use lancet; blood was collected on filtre paper specially prepared with a proprietary antioxidant. Blood acid compositions were analysed according to the HS-Omega-3 Index® methodology as described previously [ 50, 51 ]. Fatty acid methyl esters were generated by acid transesterification and analysed by gas chromatography using hydrogen as carrier gas. Fatty acids were identified by comparison with a standard mixture of fatty acids (GLC-727, Nuchek Prep, Elysian, Minnesota, USA). Results are given as the O3I, which is EPA + DHA expressed as a percentage of total identified fatty acids after response factor correction and a correction for the fact that whole blood was used instead of erythrocytes [50]. Typically, the coefficient of variation for EPA plus DHA is 5%. Analyses are quality-controlled according to DIN ISO. Furthermore, 26 other fatty acids were determined. We focussed on AA, DHA, EPA, ObA, and DPA. The O3I has been related to mental health in earlier studies investigating depression, bipolar disorder, and schizophrenia [ 52–55 ]. Questionnaires Centre for Epidemiologic Studies Depression scale Depressive feelings were assessed with the Dutch version of the CES-D scale [ 56 ], one of the most commonly used screening tools for depression that has been shown to be able to distinguish between depressed and non-depressed individuals in both clinical and community populations [ 56 ]. The questionnaire consists of 20 questions assessing whether six symptoms of depression were experienced by the participant in the last week. The CES-D has shown a high internal reliability in adolescents (α = 0.88) [ 57 ]. The measured symptoms include depressed mood, guilt/worthlessness, helplessness/hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance. For each question, the participants have to indicate whether a symptom occurred seldom or never (< 1 day), sometimes or a few times (1–2 days), often (3–4 days), or most of the time/ always (5–7 days). Each answer is scored as 0, 1, 2, or 3, respectively, and a total sum score is calculated. The score of the CES-D can thus vary between 0 and 60, with a higher score indicating more depressive feelings. It has been suggested that depression should be considered as a continuum of increasing severity [ 8 ]. Therefore, the CES-D score was taken as a continuous variable in the current study. A CES-D score of ≥ 16 is, in general, accepted as an indication of depression [ 58 ], although some have suggested that a higher cut-off point might be more appropriate in adolescents, for example, a score of ≥ 22 [ 59 ]. We used a score of ≥ 16 in descriptive analyses to indicate the number of adolescents with possible depression in our sample. The Rosenberg Self-Esteem scale Self-esteem was measured with the Dutch version of the Rosenberg Self-Esteem scale (RSE). The internal reliability for the RSE has been found to be high in adolescents (α = 0.88) [ 60, 61 ] and construct validity with other measures of self-esteem has been shown [61]. The RSE consists of 10 questions scored on a 4-point response system (from strongly disagree = 0 to strongly agree = 3) requiring participants to indicate their level of agreement with a series of statements about themselves. The total score of the RSE can vary between 0 and 30, with a higher score indicating higher self-esteem. The RSE score was also taken as a continuous variable. Additional measures Students filled out a questionnaire to assess covariates. The following variables were assessed, and included in the analyses as covariates, as they are known to be associated with depression: BMI (weight/length2, self-reported) [ 62, 63 ], sex [ 64, 65 ], age in years [ 66 ], alcohol consumption (number of days per week that alcohol was consumed times units consumed per consumption moment) [ 67 ], smoking (yes/no, yes if the participant had indicated to smoke more than 0 cigarettes per week) [ 68 ], parental level of education (subdivided into eight levels from primary school to university) [ 69 ], pubertal status according to the categorisation suggested by Petersen et al. (subdivided into five levels from prepubertal to postpubertal) [ 70 ] (association between pubertal status and depression [ 71, 72 ]), and diagnosis which might influence learning (yes/no, e.g. autism, dyslexia, ADHD) [ 73, 74 ]. Data analyses Twelve participants had a maximum of two missing data points for the CES-D, these missing points were imputed by the person average score of the other CES-D items (if necessary reversed scored) as explained by Bono et al. [ 75 ]. For the RSE the same procedure was used. For all continuous variables (all fatty acids, O3I, BMI, CES-D and RSE score) z-scores were calculated, i.e. a measure of how many standard deviations a data point is away from the mean score of the total sample. We estimated the effect sizes for the association between the fatty acids and depression score/ self-esteem using Bayesian statistical approach. This approach makes it possible to incorporate prior knowledge about relationships (called a prior), and, using a Bayes factor, to compare different models including the model representing the null hypotheses. Bayes factor10 (BF) indicates how many times the alternative hypothesis (H1, e.g. DHA is related to depression) is more likely compared to the null hypothesis (H0, e.g. DHA is not related to depression) or another hypothesis. It is, in general, accepted that a BF10 between 0.33 and 3 indicates that data do not favour either H0 or H1, the data are insensitive. A BF10 for the comparison of H1 to H0 of less than 0.33 indicates evidence in favour of the H0 and a BF10 of more than 3 indicates evidence for the H1 [ 76 ]. We considered the degree of evidence in favour of a model in accordance with Jeffrey’s classification: BF10 of 1 for no evidence; 1 to 3 (resp. when BF10 is 1/3 to 1 there is evidence in favour of null hypothesis) for anecdotal evidence in favour of alternative hypothesis; 3–10 (1/10 to 1/3) for substantial evidence; 10–30 (1/30 to 1/10) for strong evidence; 30–100 for very strong evidence, (1/100 to 1/30); > 100 (< 1/100) for extreme evidence [ 77 ]. Next to estimating BF10 indices, we also used a top-down approach in which the full model is compared with a model with all factors but one (i.e., inclusion of all fatty acids but DHA). BFomit indicates whether removing the factor from the model is deleterious, it is suggested that a BFomit < 3 indicates that the factor is beneficial for the model and a BFomit > 3 that removing the factor is better for the model [ 78 ]. Because of the same denominator, BF10 indices of different models with all possible combinations of covariates and predictors can be compared. For estimated effect sizes, a 95% credibility interval is provided that describes intervals where the parameters fall within a 95% probability given the observed data. Analyses were executed in the R statistical environment (R studio version 3.3.2) with the package BayesFactor (version 0.9.12-2). We used the standard settings of the package: the package considers the regression parameters to be distributed normally around zero, with negative effects and positive effects being equally likely, and smaller effects being more likely than larger effects. For the descriptive comparisons of characteristics between those with and without depression, ANOVA and Chi-square analyses were carried out. To explore the associations between each respective fatty acid or the O3I and depression respectively self-esteem, regression models were built predicting CES-D and RSE from the fatty acids. Next to the analyses with each fatty acid as individual predictor, two regression models were additionally built (one for depression and one for self-esteem) with all fatty acids as predictors in one analysis, which allows adjustment of the effect of a fatty acid for the effects of other fatty acids. All regression models were corrected for covariates, which were selected by comparing BFs of regression models with all possible combinations of covariates and the fatty acid. For estimation of the effect size 10.000 Monte Carlo iterations were run. Results In total, 286 students provided informed consent. For three participants no blood sample was obtained. Additionally, one participant was excluded because of severe hyperventilation after blood sampling, one participant withdrew consent before the study started, and one student quit during the first test session and was, therefore, excluded. Fourteen participants had an O3I > 5% and were, therefore, based on the protocol of the main Food2Learn study, excluded. Nine additional students did have an O3I > 5% but were not excluded before the start of the study, they were however excluded from analyses. In total 257 students started the study; however, baseline data on depression were available for 252 participants and self-esteems scores for 255 participants. Characteristics of all participants are presented in Table 1. Do note that not all participants filled out the personal questionnaire, or did not fill out all questions, and data on level of parental education (LPE) and BMI are missing for 17 participants. A total of 74 (29.4%) students (with CES-D score available) scored ≥ 16 on the CES-D indicative of a depression. When using the stricter criterion of ≥ 22, a total of 43 students (17.1%) could be classified as possibly having depression. Comparing those with a depression (CES-D ≥ 16) and those without a depression (CES-D ≤ 15), there was extreme evidence (BF10 = 1.1E + 4) that girls had more often a depression (42.3% with CES-D ≥ 16) than boys (15.6%). There was substantial evidence (BF = 5.64) that those with a depression had a higher BMI (M = 20.84, SD = 3.10) than those without depression (M = 19.64, SD = 2.93) and extreme evidence (BF10 = 3.7E + 2) that those with a depression were further in puberty (82.9% were advanced or postpubertal) than those without depression (50.9% advanced or postpubertal). There was extreme evidence (BF10 = 1.7E + 28) that self-esteem was significantly lower in those with a depression (M = 15.4, SD = 5.64) compared to those without (M = 23.88, SD = 3.96). Also when looking at the association between self-esteem and depression, their association was strong (self-esteem regressed on depression, regression coefficient = − 0.75 [95% credibility interval − 0.83 to − 0.67]; BF10 = 3.51E43). When comparing models predicting CES-D from potential confounders (namely smoking, alcohol, age, sex, BMI, LPE, pubertal status and diagnosis), the models with the highest BF10 included the variables smoking, sex and BMI. We, therefore, included these variables as covariates in the main analyses. For RSE, the best models contained smoking, sex and diagnosis, or smoking and sex. We, therefore, only included smoking, sex and diagnosis as covariates in the analyses for RSE. Excluding participants with missing data, data of 234 participants were available for CESD and data of 253 participants for RSE. Individual models that predicted CES-D scores from a fatty acid showed negative regression coefficients with 95% credibility intervals without zero for AA [regression coefficient= − 0.14 (95% credibility interval − 0.26 to − 0.03); BF10 = 2.37], DPA [− 0.13 (− 0.25 to − 0.02); BF10 = 1.08], and ObA [− 0.16 (− 0.28 to − 0.05); BF10 = 350.04] (Table 2). This indicates that higher levels of these fatty acids in blood are associated with lower depression scores. However, BF10 indicated evidence in favour of the association for ObA only (extreme evidence, BF10 > 100). For AA and DPA, BF10 showed anecdotal evidence in favour of the alternative hypothesis. The BF10 for O3I and DHA were below 0.33, which indicates that there is more evidence for the H0, i.e., no association between O3I and DHA, and depression. When all fatty acids were taken in one model as predictors of CES-D (BF10 for the model = 2.4E + 5), the regression coefficient for ObA became smaller and its 95% CI contained a zero score [− 0.10 (− 0.22 to 0.03)] (Table 2). The regression coefficient of DPA was almost identical to that in N Mean SD LPE level of parental education, O3I Omega-3 Index aSmoking was defined as anybody who indicated to smoke more than zero cigarettes per week bAlcohol units per week was operationalized as number of day per week that alcohol is consumed times units per consumption moment the individual model − 0.12 (− 0.25 to 0.02), but 95% CI for DPA, as well as for all other fatty acids, contained zero. The BFomit indicated that the model would be improved when DHA was omitted (BFomit > 3). For other acids, BFomit indices were not higher than 3 or lower than 0.33, thus removing them would not improve or worsen the model. Bayesian analyses for regressions that predicted the RSE score showed no 95% CIs that did not include zero (Table 3). When looking at the Bayes factors, there was only substantial evidence for an association between ObA and RSE (BF10 = 4.36), for all other fatty acids, and the O3I, BF10 was below 0.33 which indicates more evidence for the H0, i.e., no association between fatty acids and selfesteem. When all fatty acids were taken in one model as predictors of RSE, BFomit for DHA exceeded the threshold values (> 3), which indicates that removing this from the model would improve the model that contains all fatty acids. One fatty acid model is a model in which only one predictor of interest is entered (Omega-3 Index, DHA, EPA AA, DPA or ObA). All fatty acids model is a model in which all fatty acids (DHA, EPA, AA, DPA and ObA) are entered, i.e., for example the association between DHA and self-esteem is corrected for the other fatty acids (EPA, AA, DPA, ObA) All analyses were adjusted for smoking (yes/no), sex and diagnosis (yes/no) RSE Rosenberg Self-Esteem scale aCredibility intervals are analogous to confidence intervals in traditional statistics bBF10 refers to the evidence for the model with the specific fatty acid compared to a model with only covariates cBFomit indicates whether the model improves with the omission of that specific fatty acid. BF omit above 3 indicate that keeping the variable in the model is not preferable One fatty acid model is a model in which only one predictor of interest is entered (Omega-3 Index, DHA, EPA, AA, DPA, or ObA). All fatty acids model is a model in which all fatty acids (DHA, EPA, AA, DPA, and ObA) are entered, i.e., for example the association between DHA and self-esteem is corrected for the other fatty acids (EPA, AA, DPA, ObA) All analyses were adjusted for BMI, smoking (yes/no), and sex O3I Omega-3 Index, CES-D Centre for Epidemiologic Studies Depression scale aCredibility intervals are analogous to confidence intervals in traditional statistics bBF10 refers to the evidence for the model with the specific fatty acid compared to a model with only covariates cBFomit indicates whether the model improves with the omission of that specific fatty acid. BFomit numbers above 3 indicate that keeping the variable in the model is not preferable Discussion Analyses showed Bayes factors that indicated extreme evidence for a weak negative association between ObA levels and depression score, and substantial evidence for a weak positive association between ObA and self-esteem score. In other words, more ObA measured in blood corresponded with lower depression and higher self-esteem scores. There was no substantial evidence for an association between any of the other fatty acids and depression/ self-esteem. For DHA, EPA, and O3I there was even evidence for the absence of an association. When the associations of fatty acids were adjusted for each other’s effects, all effect sizes for tested associations decreased and 95% credible intervals for regression coefficients contained a zero-score. Note that additional non-linear analyses with quadratic fatty acid concentrations (not reported here) did not show evidence for a quadratic effect. The evidence for the relation of depression score with DHA, EPA and O3I in the current study was in favour of the null hypothesis (i.e., no association). Some earlier studies in adolescents that used the frequentist hypothesis testing showed non-significant associations between fatty acids and depression score [ 38, 79 ]. However, the disadvantage of the frequentist hypothesis testing approach is that a non-significant result can either imply that there is evidence for the null hypothesis (i.e., there is no association) or the data are insensitive in distinguishing the theory from the null hypothesis (i.e., nothing follows from the data) [80]. Our findings are in contrast to another earlier study in adolescents from the general population in which an negative association between depression measured with the Beck Depression Inventory (BDI) and EPA in adipose tissue of adolescents was found (i.e., more EPA, lower depression score; analysis was controlled for other fatty acids but no correction for multiple testing) [ 81 ]. However, some researchers have suggested that the CES-D, like used in our study, is better at discriminating depression at lower levels than the BDI and the CES-D, thus, might be a better measure of depression in the general population [ 82, 83 ]. Furthermore, an association between adipose fatty acids and brain fatty acids has, to our knowledge, not been established, while the association between blood levels and brain levels has been established in animal studies [84]. Blood levels of fatty acids might, therefore, be a better measure for assessing the association between fatty acids and depressive feelings. It is remarkable that the negative associations of ObA with depression and self-esteem score became less convincing and the relationship between ObA and depression score became weaker after correction for other fatty acids. We are not aware of earlier studies reporting the association between ObA and depression score, although studies looking at other omega-6 fatty acids mostly showed positive associations (i.e., more omega-6 fatty acids, higher depression scores) [ 85, 86 ]. ObA can, in the case of DHA deficiency, take the place of DHA in the brain [87]. Possibly the replacement of DHA by ObA does not change the brain functionality and, therefore, a negative association between ObA and depression score in the case of DHA deficiency can be found. This surprising negative association between ObA and depression score does merit more research. Our data provided evidence for absence of associations of depression score with DHA, EPA and O3I in this adolescent sample, while meta-analyses that included studies in adults have shown that LCPUFA supplementation is associated with less depressive feelings [ 42, 88, 89 ]. One of the possible explanations for an absent relationship in the current study could be that the design of this trial led us to preselect participants with an O3I ≤ 5%. In other fatty acid studies, it has been suggested that positive associations with O3I are only visible at higher O3I levels (i.e., 8% and up). For example, in cardiovascular health, an O3I of > 8% is associated with the greatest risk reduction and the study of Markhus et al. showed a linear relation between O3I and depressive symptoms during pregnancy only when the O3I was > 5.1% [ 50, 52 ]. Such O3I values seem rare in the specific population of students of LGSE as we only had to exclude 23 out of 286 students for having an O3I > 5%, with the highest O3I being around 6.09%. So, such a low O3I seems to be reality in this specific target group. Furthermore, whenever an effect of omega-3 fatty acids in trials is found it is mostly a small effect, which was also true in this sample where the effect sizes ranged between 0.001 and 0.15. Such a small effect could easily be offset by other environmental factors. This might especially be the case in adolescence, a period of life characterised by profound changes in brain development, but also social and emotional behaviour [ 90, 91 ]. Another important issue to consider is that most of the studies looking at depression that find significant associations find very small effect sizes and do not use Bayesian statistics. In the current study, we did find some regression coefficients with 95% CI that did not include 0 (e.g. AA and DPA predicting depression score). ‘Frequentist’ regressions with SPSS software showed comparable regression coefficients that were significant (not shown). However, Bayesian analyses only revealed anecdotal evidence for these associations. This could also be the case for other studies that found significant associations. This study showed that depressive feelings are common in adolescents of LGSE; in our sample 29.4% of the adolescents scored ≥ 16 on the CES-D which is indicative for a depression. When we used a stricter cut-off point (as some suggest for adolescents) of ≥ 22, 17.1% had scores indicative of depression. Although the percentage of adolescents with depression in this sample seems to be high, it is similar to percentages found in earlier studies in adolescents. Munhoz et al., for example, showed that 17% of the Brazilian adolescents had scores indicative for major depression [ 92 ]. Grant and colleagues (2015) also showed numbers comparable to the current study with 22% of the boys and 34.4% of girls showing depressive symptoms [ 93 ], and Mamalakis et al. (2016) observed a similar mean CES-D score (mean of 14.9 compared to 12.2 in our sample) [ 81 ]. Furthermore, it has long been known that, from age 13–14 years onward, there is a female preponderance of depression [ 94 ]. We also showed that girls in this sample had a higher incidence of depression than boys. In the current study, 42.3% of the girls had an indication for depression while, for boys, this was 15.6%. This observational study has a number of limitations. The low O3I of the participants and low spread in the O3I could have led to low statistical power. However, as we explained above, the low O3I seems to be the reality in this specific target group. Additionally, covariates included in the analysis such as smoking behaviour, drinking behaviour were assessed via self-reports, this could possible lead to bias in these covariates. Also note that the recruitment rate (i.e., percentage of those invited who decided to participate) was approximately 13%, this could limit the external validity. However, such recruitment rate is rather common in a school setting [ 95 ]. Moreover, this was a cross-sectional study and can thus not be used for proving causal relationships, experimental studies are needed for more insight in the effects of fatty acids in depression and self-esteem in this specific target group. One of the main strengths of the current study is the use of finger prick blood samples to determine the fatty acids status of the adolescents. Moreover, the population was rather homogenous and this study is one of the first specifically focusing on adolescents of a lower education level. Furthermore, we used the Bayesian approach that, in contrast to the frequentist approach, can be used to provide evidence for the null hypothesis and to compare different models without issues concerning multiple testing. To summarise, our data in Dutch LGSE adolescents with a low O3I in blood revealed high depression rates and provided extreme evidence for a weak association between ObA levels and depression score (more ObA, lower depression score) and substantial evidence for a weak association between ObA and self-esteem score (more ObA, higher selfesteem). This surprising result calls for more research into the role of ObA in depression. Results of the intervention study Food2Learn should shed light on the effect of krill oil supplementation (high in omega-3 fatty acids) on depressive feelings in adolescents of the LGSE. Acknowledgements We like to thank all participants and schools who participated in Food2Learn. Furthermore, we like to thank the dedicated research assistants: Marije Broens-Paffen, Denise Hofman and Annemarijn Weber. Funding The study is funded by the Grant Food, Cognition and Behaviour from the Dutch Scientific Organisation (Grant number 057-13002), Aker Biomarine (Norway) who provided the krill and placebo capsules, and Omegametrix (Germany) who was responsible for the blood analyses. CVS is owner of Omegametrix, who is responsible for the blood analyses in this study. TB is a former employee of Aker Biomarine, who is partly funding the study. Compliance with ethical standards Conflict of interest All other authors declare no conflict of interest. The sponsor had no role in the collection, analyses, or interpretation of data. Ethical approval Food2Learn was approved by the Medical Ethical Committee of Atrium-Orbis-Zuyd Hospital Heerlen, the Netherlands (NL45803.096.13). Informed consent Each participant as well as parent(s) and/or guardian(s) provided written informed consent for participation in the study. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativeco mmons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 1 3 1. Marcus M , Yasamy MT , van Ommeren M , Chisholm D ( 2012 ) Depression, a global public health concern . WHO Department of Mental Health and Substance Abuse , pp 1 - 8 . http://www.who. int/mental_health/management/depression/who_paper_depression _wfmh_ 2012 .pdf 2. Grosso G , Galvano F , Marventano S et al ( 2014 ) Omega-3 fatty acids and depression: scientific evidence and biological mechanisms . Oxid Med Cell Longev 2014 : 313570 3. Kessler RC , Walters EE ( 1998 ) Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey . Depress Anxiety 7 : 3 - 14 4. Fröjd SA , Nissinen ES , Pelkonen MUI et al ( 2008 ) Depression and school performance in middle adolescent boys and girls . J Adolesc 31 : 485 - 498 5. Fergusson DM , Woodward LJ ( 2002 ) Mental health, educational, and social role outcomes of adolescents with depression . Arch Gen Psychiatry 59 : 225 6. McLeod GFH , Horwood LJ , Fergusson DM ( 2016 ) Adolescent depression, adult mental health and psychosocial outcomes at 30 and 35 years . Psychol Med 46 : 1401 - 1412 7. Pelkonen M , Marttunen M , Aro H ( 2003 ) Risk for depression: a 6-year follow-up of Finnish adolescents . J Affect Disord 77 : 41 - 51 8. Wesselhoeft R , Sørensen MJ , Heiervang ER , Bilenberg N ( 2013 ) Subthreshold depression in children and adolescents - a systematic review . J Affect Disord 151 : 7 - 22 9. Bertha EA , Balázs J ( 2013 ) Subthreshold depression in adolescence: a systematic review . Eur Child Adolesc Psychiatry 22 : 589 - 603 10. Fergusson DM , Horwood LJ , Ridder EM , Beautrais AL ( 2005 ) Subthreshold depression in adolescence and mental health outcomes in adulthood . Arch Gen Psychiatry 62 : 66 - 72 11. Sullivan PF , Neale MC , Kendler KS ( 2000 ) Genetic epidemiology of major depression: review and meta-analysis . Am J Psychiatry 157 : 1552 - 1562 12. Norman RE , Byambaa M , De R et  al ( 2012 ) The long-term health consequences of child physical abuse, emotional abuse, and neglect: a systematic review and meta-analysis . PLoS Med 9 : e1001349 13. Kendler KS , Kessler RC , Waiters EE et  al ( 1995 ) Stressful life events, genetic liability, and onset of an episode of major depression in women . Am J Psychiatry 152 : 833 - 842 14. Kessler RC ( 1997 ) The effects of stressful live events on depression . Annu Rev Psychol 48 : 191 - 214 15. Tafet GE , Bernardini R ( 2003 ) Psychoneuroendocrinological links between chronic stress and depression . Prog Neuro-Psychopharmacol Biol Psychiatry 27 : 893 - 903 16. Maes M , Yirmyia R , Noraberg J et al ( 2009 ) The inflammatory and neurodegenerative (I&ND)hypothesis of depression: leads for future research and new drug developments in depression . Metab Brain Dis 24 : 27 - 53 17. Folstein M , Liu T , Peter I et  al ( 2007 ) The homocysteine hypothesis of depression . Am J Psychiatry 164 : 861 - 867 18. Drevets WC ( 2000 ) Neuroimaging studies of mood disorders . Biol Psychiatry 48 : 813 - 829 19. Schiepers OJG , Wichers MC , Maes M ( 2005 ) Cytokines and major depression . Prog Neuro-Psychopharmacol Biol Psychiatry 29 : 201 - 217 20. Campbell S , MacQueen G ( 2006 ) An update on regional brain volume differences associated with mood disorders . Curr Opin Psychiatry 19 : 25 - 33 21. Drevets WC , Price JL , Simpson JR Jr et al ( 1997 ) Subgenual prefrontal cortex abnormalities in mood disorders . Nature 386 : 824 - 827 22. Parletta N , Milte C , Meyer BJ ( 2013 ) Nutritional modulation of cognitive function and mental health . J Nutr Biochem 24 : 725 - 743 23. Assisi A , Banzi R , Buonocore C et al ( 2006 ) Fish oil and mental health: the role of n-3 long-chain polyunsaturated fatty acids in cognitive development and neurological disorders . Int Clin Psychopharmacol 21 : 319 - 336 24. Rechenberg K ( 2016 ) Nutritional interventions in clinical depression . Clin Psychol Sci 4 : 144 - 162 25. Lin P-Y , Huang S-Y , Su K-P ( 2010 ) A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression . Biol Psychiatry 68 : 140 - 147 26. Riemer S , Maes M , Christophe A , Rief W ( 2010 ) Lowered omega-3 PUFAs are related to major depression, but not to somatization syndrome . J Affect Disord 123 : 173 - 180 27. Tiemeier H , van Tuijl HR , Hofman A et al ( 2003 ) Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam study . Am J Clin Nutr 78 : 40 - 46 28. McNamara RK , Hahn C-G , Jandacek R et al ( 2007 ) Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder . Biol Psychiatry 62 : 17 - 24 29. Lin P-Y , Su K-P ( 2007 ) A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids . J Clin Psychiatry 68 : 1056 - 1061 30. Jazayeri S , Tehrani-Doost M , Keshavarz S et al ( 2008 ) Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder . Aust N Z J Psychiatry 42 : 192 - 198 31. Mischoulon D , Best-Popescu C , Laposata M et  al ( 2008 ) A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder . Eur Neuropsychopharmacol 18 : 639 - 645 32. Grosso G , Pajak A , Marventano S et al ( 2014 ) Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials . PLoS One 9 : e96905 33. Rogers PJ , Appleton KM , Kessler D et al ( 2008 ) No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial . Br J Nutr 99 : 421 - 431 34. Grenyer BFS , Crowe T , Meyer B et al ( 2007 ) Fish oil supplementation in the treatment of major depression: a randomised doubleblind placebo-controlled trial . Prog Neuropsychopharmacol Biol Psychiatry 31 : 1393 - 1396 35. Tsuchimine S , Saito M , Kaneko S , Yasui-Furukori N ( 2015 ) Decreased serum levels of polyunsaturated fatty acids and folate, but not brain-derived neurotrophic factor, in childhood and adolescent females with depression . Psychiatry Res 225 : 187 - 190 36. Pottala J , Talley J , Churchill S et al ( 2012 ) Red blood cell fatty acids are associated with depression in a case-control study of adolescents . Prostaglandins Leukot Essent Fat Acids 86 : 161 - 165 37. Murakami K , Miyake Y , Sasaki S et al ( 2010 ) Fish and n-3 polyunsaturated fatty acid intake and depressive symptoms: Ryukyus Child Health Study . Pediatrics 126 : e623 - 630 38. Oddy WH , Hickling S , Smith MA et al ( 2011 ) Dietary intake of omega-3 fatty acids and risk of depressive symptoms in adolescents . Depress Anxiety 28 : 582 - 588 39. Crowe FL , Skeaff CM , Green TJ , Gray AR ( 2007 ) Serum phospholipid n 3 long-chain polyunsaturated fatty acids and physical and mental health in a population-based survey of New Zealand adolescents and adults . Am J Clin Nutr 86 : 1278 - 1285 40. Fryers T , Melzer D , Jenkins R ( 2003 ) Social inequalities and the common mental disorders-a systematic review of the evidence . Soc Psychiatry Psychiatr Epidemiol 38 : 229 - 237 41. Topuzoğlu A , Binbay T , Ulaş H et al ( 2015 ) The epidemiology of major depressive disorder and subthreshold depression in Izmir, Turkey: prevalence, socioeconomic differences, impairment and help-seeking . J Affect Disord 181 : 78 - 86 42. Parker G , Neville Gibson FA , Brotchie H et al ( 2006 ) Omega-3 fatty acids and mood disorders . Am J Psychiatry 1636 : 969 - 978 43. Neuringer M. Connor WE. Lin DS . Barstad L. Luck S ( 1986 ) Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys . Proc Natl Acad Sci USA 83 : 4021 - 4025 44. Orth U , Robins RW , Roberts BW ( 2008 ) Low self-esteem prospectively predicts depression in adolescence and young adulthood . J Pers Soc Psychol 95 : 695 - 708 45. Orth U , Robins RW , Widaman KF ( 2012 ) Life-span development of self-esteem and its effects on important life outcomes . J Pers Soc Psychol 102 : 1271 - 1288 46. Orth U , Robins RW , Widaman KF , Conger RD ( 2014 ) Is low selfesteem a risk factor for depression? Findings from a longitudinal study of Mexican-origin youth . Dev Psychol 50 : 622 - 633 47. Trzesniewski KH , Donnellan MB , Moffitt TE et al ( 2006 ) Low self-esteem during adolescence predicts poor health, criminal behavior, and limited economic prospects during adulthood . Dev Psychol 42 : 381 - 390 48. van der Wurff ISM , von Schacky C , Berge K et al ( 2016 ) A protocol for a randomised controlled trial investigating the effect of increasing Omega-3 index with krill oil supplementation on learning, cognition, behaviour and visual processing in typically developing adolescents . BMJ Open 6 : e011790 49. Centraal Bureau Voor de Statistiek (Statistics Netherlands) VO ; leerlingen, onderwijssoort in detail, leerjaar (Secondary education, students, type of education in detail per teaching year) . http://statl ine.cbs.nl/StatWeb/publication/?VW= T&DM=SLnl&PA=80040 NED&LA=nl . Accessed 22 Jul 2015 50. Harris WS , Von Schacky C ( 2004 ) The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med 39 : 212 - 220 51. Harris WS , von Schacky C , Park Y ( 2013 ) Standardizing methods for assessing omega-3 fatty acid biostatus . In: McNamara RK (ed) The omega-3 fatty acid deficiency syndrome: opportunities for disease prevention . Nova Science Publishers, Inc, Hauppauge, pp 385 - 398 52. Markhus MW , Skotheim S , Graff IE et al ( 2013 ) Low omega-3 index in pregnancy is a possible biological risk factor for postpartum depression . PLoS One 8 : e67617 53. Parletta N , Zarnowiecki D , Cho J et al ( 2016 ) People with schizophrenia and depression have a low omega-3 index. Prostaglandins Leukot Essent Fat Acids . https://doi.org/10.1016/j.plefa . 2016 . 05 .007 54. Mcnamara RK , Jandacek R , Tso P et al ( 2016 ) Adolescents with or at ultra-high risk for bipolar disorder exhibit erythrocyte docosahexaenoic acid and eicosapentaenoic acid deficits: a candidate prodromal risk biomarker . Early Interv Psychiatry . https://doi. org/10.1111/eip.12282 55. Bigornia SJ , Harris WS , Falcon LM et al ( 2016 ) The omega-3 index is inversely associated with depressive symptoms among individuals with elevated oxidative stress biomarkers . J Nutr . https ://doi.org/10.3945/jn.115.222562 56. Radloff LS ( 1977 ) The CES-D Scale: a self-report depression scale for research in the general population . Appl Psychol Meas 1 : 385 - 401 57. Stockings E , Degenhardt L , Lee YY et al ( 2015 ) Symptom screening scales for detecting major depressive disorder in children and adolescents: a systematic review and meta-analysis of reliability, validity and diagnostic utility . J Affect Disord 174 : 447 - 463 58. Beekman A , Deeg DJ , Van Limbeek J et al ( 1997 ) Criterion validity of the center for epidemiologic studies depression scale (CESD): results from a community-based sample of older subjects in The Netherlands . Psychol Med 27 : 231 - 235 59. Cuijpers P , Boluijt P , Van Straten A ( 2008 ) Screening of depression in adolescents through the Internet: sensitivity and specificity of two screening questionnaires . Eur Child Adolesc Psychiatry 17 : 32 - 38 60. Gray-Little B , Williams VSL , Hancock TD ( 1997 ) An Item response theory analysis of the Rosenberg self-esteem scale . Personal Soc Psychol Bull 23 : 443 - 451 61. Robins RW , Hendin HM , Trzesniewski KH ( 2001 ) Measuring global self-esteem: construct validation of a single-item measure and the Rosenberg self-esteem scale . Personal Soc Psychol Bull 27 : 151 - 161 62. Atlantis E , Baker M ( 2008 ) Obesity effects on depression: systematic review of epidemiological studies . Int J Obes 32 : 881 - 891 63. Cortese S , Falissard B , Angriman M et al ( 2009 ) The relationship between body size and depression symptoms in adolescents . J Pediatr 154 : 86 - 90 64. Allgood-Merten B , Lewinsohn PM , Hops H ( 1990 ) Sex differences and adolescent depression . J Abnorm Psychol 99 : 55 - 63 65. Wichstrøm L ( 1999 ) The emergence of gender difference in depressed mood during adolescence: the role of intensified gender socialization . Dev Psychol 35 : 232 - 245 66. Hankin BL , Abramson LY , Moffitt TE et al ( 1998 ) Development of depression from preadolescence to young adulthood: emerging gender differences in a 10-year longitudinal study . J Abnorm Psychol 107 : 128 - 140 67. Skogen JC , Knudsen AK , Hysing M et al ( 2016 ) Trajectories of alcohol use and association with symptoms of depression from early to late adolescence: the Norwegian longitudinal health behaviour study . Drug Alcohol Rev 35 : 307 - 316 68. Munafò MR , Hitsman B , Rende R et al ( 2008 ) Effects of progression to cigarette smoking on depressed mood in adolescents: evidence from the National Longitudinal Study of Adolescent Health . Addiction 103 : 162 - 171 69. Goodman E , Slap GB , Huang B ( 2003 ) The public health impact of socioeconomic status on adolescent depression and obesity . Am J Pub Health 93 : 1844 - 1850 70. Petersen AC , Crockett L , Richards M , Boxer A ( 1988 ) A selfreport measure of pubertal status: reliability, validity, and initial norms . J Youth Adolesc 17 : 117 - 133 71. Hayward C , Gotlib IANH. , Ph D et al ( 1999 ) Ethnic differences in the association between pubertal status and symptoms of depression in adolescent girls . J Adolesc Health 25 : 143 - 149 72. Angold A , Costello EJ , Worthman CM ( 1998 ) Puberty and depression: the roles of age, pubertal status and pubertal timing . Psychol Med 28 : 51 - 61 . https://doi.org/10.1017/S003329179700593X 73. Biederman J , Ball SW , Monuteaux MC et al ( 2008 ) New insights into the comorbidity between ADHD and major depression in adolescent and young adult females . J Am Acad Child Adolesc Psychiatry 47 : 426 - 434 74. Zakopoulou V , Mavreas V , Christodoulides P et al ( 2014 ) Specific learning difficulties: a retrospective study of their co morbidity and continuity as early indicators of mental disorders . Res Dev Disabil 35 : 3496 - 3507 . https://doi.org/10.1016/j.ridd. 2014 . 07 .040 75. Bono C , Ried LD , Kimberlin C , Vogel B ( 2007 ) Missing data on the center for epidemiologic studies depression scale: a comparison of 4 imputation techniques . Res Soc Adm Pharm 3 : 1 - 27 76. Rouder JN , Morey RD ( 2012 ) Default Bayes factors for model selection in regression . Multivar Behav Res 47 : 877 - 903 77. Wagenmakers E , Wetzels R , Borsboom D , van der Maas HLJ ( 2011 ) Why psychologists must change the way they analyze their data: the case of psi: comment on Bem ( 2011 ). J Pers Soc Psychol 100 : 426 - 432 . https://doi.org/10.1037/a0022790 78. Morey RD Using the “BayesFactor” package , version 0.9.2 79. Mamalakis G , Kiriakakis M , Tsibinos G , Kafatos A ( 2004 ) Depression and adipose polyunsaturated fatty acids in an adolescent group . Prostaglandins Leukot Essent Fat Acids 71 : 289 - 294 80. Dienes Z ( 2014 ) Using Bayes to get the most out of non-significant results . Front Psychol 5 : 781 81. Mamalakis G , Kiriakakis M , Tsibinos G et al ( 2006 ) Depression and serum adiponectin and adipose omega-3 and omega-6 fatty acids in adolescents . Pharmacol Biochem Behav 85 : 474 - 479 82. Santor D , Zuroff DC , Ramsay JO et al ( 1995 ) Examining scale discriminability in the BDI and CES-D as a function of depressive severity . Psychol Assess 7 : 131 - 139 83. Olino TM , Yu L , Klein DN et al ( 2012 ) Measuring depression using item response theory: an examination of three measures of depressive symptomatology . Int J Methods Psychiatr Res 21 : 76 - 85 84. Connor WE , Neuringer M , Lin DS ( 1990 ) Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys . J Lipid Res 31 : 237 - 247 85. Conklin SM , Manuck SB , Yao JK et al ( 2007 ) High ω-6 and low ω-3 fatty acids are associated with depressive symptoms and neuroticism . Psychosom Med 69 : 932 - 934 86. Wolfe AR , Ogbonna EM , Lim S et al ( 2009 ) Dietary linoleic and oleic fatty acids in relation to severe depressed mood: 10 years follow-up of a national cohort . Prog Neuro-Psychopharmacol Biol Psychiatry 33 : 972 - 977 87. Kim H-Y , Bigelow J , Kevala JH ( 2004 ) Substrate preference in phosphatidylserine biosynthesis for docosahexaenoic acid containing species . Biochemistry 43 : 1030 - 1036 88. Sublette ME , Ellis SP , Geant AL , Mann JJ ( 2011 ) Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression . J Clin Psychiatry 72 : 1577 - 1584 89. Appleton KM , Rogers PJ , Ness AR ( 2010 ) Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood . Am J Clin Nutr 91 : 757 - 770 90. Crone EA , Dahl RE ( 2012 ) Understanding adolescence as a period of social-affective engagement and goal flexibility . Nat Rev Neurosci 13 : 636 - 650 91. Gogtay N , Giedd JN , Lusk L et al ( 2004 ) Dynamic mapping of human cortical development during childhood through early adulthood . Proc Natl Acad Sci USA 101 : 8174 - 8179 92. Munhoz TN , Santos IS , Matijasevich A ( 2013 ) Major depressive episode among Brazilian adults: a cross-sectional populationbased study . J Affect Disord 150 : 401 - 407 93. Grant R , Bilgin A , Guest J et al ( 2015 ) The relative value of measures of omega-3 index, perceived stress, cortisol and sleep time in identifying depression among a cohort of Australian adolescents . Int J Child Health Nutr 4 : 40 - 49 94. Nolen-Hoeksema S , Girgus JS ( 1994 ) Emergence of gender differences in depression during adolescence . Psychol Bull 115 : 423 - 443 95. van der Wurff ISM , Meyer BJ , de Groot RHM ( 2017 ) A review of recruitment, adherence and drop-out rates in omega-3 polyunsaturated fatty acid supplementation trials in children and adolescents . Nutrients 9 : 474

This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1007%2Fs00394-018-1667-4.pdf

I. S. M. van der Wurff, C. von Schacky, T. Bergeland, R. Leontjevas, M. P. Zeegers, P. A. Kirschner, R. H. M. de Groot. Exploring the association between whole blood Omega-3 Index, DHA, EPA, DHA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education, European Journal of Nutrition, 2018, 1-11, DOI: 10.1007/s00394-018-1667-4