Genomics Research of Lifetime Depression in the Netherlands: The BIObanks Netherlands Internet Collaboration (BIONIC) Project.

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.

Soft Drinks and Symptoms of Depression and Anxiety in Overweight Subjects: A Longitudinal Analysis of an European Cohort.

BACKGROUND: Studies about the association of carbonated/soft drinks, coffee, and tea with depression and anxiety are scarce and inconclusive and little is known about this association in European adults. Our aim was to examine the association between the consumption of these beverages and depressive and anxiety symptom severity. METHODS: A total of 941 European overweight adults (mean age, 46.8 years) with subsyndromal depression that participated in the MooDFOOD depression prevention randomized controlled trial (Clinical Trials.gov identifier: NCT2529423; date of the study: from 2014 to 2018) were analyzed. Depressive and anxiety symptom severity and beverage consumption were assessed using multilevel mixed-effects ordinal logistic regression models for each beverage consumption (carbonated/soft drink with sugar, carbonated/soft drink with non-nutritive sweeteners, coffee, and tea) with the three repeated measures of follow-up (baseline and 6 and 12 months). A case report form for participants' sociodemographic and clinical characteristics, the Food Frequency Questionnaire, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder 7-Item Scale, the MINI International Neuropsychiatric Interview 5.0, the Short Questionnaire to Assess Health-Enhancing Psychical Activity, and the Alcohol Use Disorders Identification Test were the research tools used. RESULTS: Daily consumption of carbonated/soft drinks with sugar was associated with a higher level of anxiety. Trends towards significance were found for associations between both daily consumption of carbonated/soft drinks with sugar and non-nutritive sweeteners and a higher level of depression. No relationship was found between coffee and tea consumption and the level of depression and anxiety. CONCLUSIONS: The high and regular consumption of carbonated/soft drink with sugar (amount of consumption: ≥1 unit (200 mL)/day) tended to be associated with higher level of anxiety in a multicountry sample of overweight subjects with subsyndromal depressive symptoms. It is important to point out that further research in this area is essential to provide valuable information about the intake patterns of non-alcoholic beverages and their relationship with affective disorders in the European adult population.

Prevalence, associations and health outcomes of binge eating in adults with type 1 or type 2 diabetes: Results from Diabetes MILES - The Netherlands.

AIMS: To examine the prevalence and health risks of binge eating in people with diabetes. METHODS: Self-report data were analysed from a subsample (n = 582 type 1 diabetes/735 type 2 diabetes) of Diabetes MILES - the Netherlands, an online survey. Prevalence of binge eating was compared across diabetes type and treatment and between participants with and without binges for eating styles, diabetes treatment and outcomes, weight, BMI and psychological comorbidity. Associations between binge eating, HbA1c , BMI, diabetes distress were assessed using hierarchical linear regression analyses. RESULTS: 23% (n = 308) of participants reported eating binges, with 16% at least monthly, and 6% at least weekly. Prevalence and frequency of binges did not differ across diabetes type or treatment. People reporting binges scored higher on dietary restraint, emotional and external eating and reported higher weight and BMI than those without binges. Only people with type 1 diabetes and eating binges had a higher HbA1c . Hierarchical regression analyses demonstrated that binge eating was independently associated with higher HbA1c (ß = 0.12, p=0.001), BMI (ß = 0.13, p < 0.001) but not with diabetes distress. CONCLUSIONS: This study found binge eating to be associated with eating styles, BMI and HbA1c . However, our cross-sectional data do not allow for conclusions on causality. Future studies could further examine the directions of these associations and their clinical implications.

Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms: A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts.

BACKGROUND: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share sociodemographic, lifestyle and clinical characteristics. METHODS: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed. RESULTS: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17). CONCLUSIONS: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point.

Flourishing mental health and lifestyle behaviours in adults with Type 1 and Type 2 Diabetes Mellitus: results from the Diabetes MILES - The Netherlands Study.

OBJECTIVE: To examine the associations between mental health and lifestyle in adults with type 1 and type 2 diabetes mellitus (T1DM and T2DM). METHODS: Online survey data from the cross-sectional Diabetes MILES - The Netherlands Study was analysed, including 270 adults with T1DM and 325 with T2DM. Mental health status (flourishing, moderate and languishing) in relation to diet, physical activity, alcohol consumption and smoking was analysed with ANCOVA and logistic regressions (adjusted for confounders). RESULTS: 47% of T1DM-, and 55% of T2DM participants reported flourishing mental health. Due to an insufficient number, participants with languishing mental health were excluded. In T2DM, participants with flourishing mental health had more optimal diet quality (mean ± SEM: 70 ± 1 vs 68 ± 1 diet quality score, p = 0.015), and physical activity levels (mean ± SEM: 3484 ± 269 vs 2404 ± 273 MET minutes/week, p = 0.001) than those with moderate mental health, but did not differ with respect to alcohol consumption and smoking. In T1DM, no significant associations were found. CONCLUSION: Only in T2DM, people with flourishing mental health had more optimal lifestyle behaviours compared to people with moderate mental health. Further research is needed to determine if mental health is more important for specific lifestyle behaviours, and if the mental health effect differs across diabetes types.

Fat metabolism is associated with telomere length in six population-based studies.

Telomeres are repetitive DNA sequences located at the end of chromosomes, which are associated to biological aging, cardiovascular disease, cancer and mortality. Lipid and fatty acid metabolism have been associated with telomere shortening. We have conducted an in-depth study investigating the association of metabolic biomarkers with telomere length (LTL). We performed an association analysis of 226 metabolic biomarkers with LTL using data from 11 775 individuals from six independent population-based cohorts (BBMRI-NL consortium). Metabolic biomarkers include lipoprotein lipids and subclasses, fatty acids, amino acids, glycolysis measures and ketone bodies. LTL was measured by quantitative polymerase chain reaction or FlowFISH. Linear regression analysis was performed adjusting for age, sex, lipid-lowering medication and cohort-specific covariates (model 1) and additionally for body mass index (BMI) and smoking (model 2), followed by inverse variance-weighted meta-analyses (significance threshold Pmeta = 6.5 × 10-4). We identified four metabolic biomarkers positively associated with LTL, including two cholesterol to lipid ratios in small VLDL (S-VLDL-C % and S-VLDL-CE %) and two omega-6 fatty acid ratios (FAw6/FA and LA/FA). After additionally adjusting for BMI and smoking, these metabolic biomarkers remained associated with LTL with similar effect estimates. In addition, cholesterol esters in very small VLDL (XS-VLDL-CE) became significantly associated with LTL (P = 3.6 × 10-4). We replicated the association of FAw6/FA with LTL in an independent dataset of 7845 individuals (P = 1.9 × 10-4). To conclude, we identified multiple metabolic biomarkers involved in lipid and fatty acid metabolism that may be involved in LTL biology. Longitudinal studies are needed to exclude reversed causation.

Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling.

BACKGROUND: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. METHODS: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. RESULTS: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59). CONCLUSIONS: Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk.

Effects of dietary interventions on depressive symptom profiles: results from the MooDFOOD depression prevention study.

BACKGROUND: Dietary interventions did not prevent depression onset nor reduced depressive symptoms in a large multi-center randomized controlled depression prevention study (MooDFOOD) involving overweight adults with subsyndromal depressive symptoms. We conducted follow-up analyses to investigate whether dietary interventions differ in their effects on depressive symptom profiles (mood/cognition; somatic; atypical, energy-related). METHODS: Baseline, 3-, 6-, and 12-month follow-up data from MooDFOOD were used (n = 933). Participants received (1) placebo supplements, (2) food-related behavioral activation (F-BA) therapy with placebo supplements, (3) multi-nutrient supplements (omega-3 fatty acids and a multi-vitamin), or (4) F-BA therapy with multi-nutrient supplements. Depressive symptom profiles were based on the Inventory of Depressive Symptomatology. RESULTS: F-BA therapy was significantly associated with decreased severity of the somatic (B = -0.03, p = 0.014, d = -0.10) and energy-related (B = -0.08, p = 0.001, d = -0.13), but not with the mood/cognition symptom profile, whereas multi-nutrient supplementation was significantly associated with increased severity of the mood/cognition (B = 0.05, p = 0.022, d = 0.09) and the energy-related (B = 0.07, p = 0.002, d = 0.12) but not with the somatic symptom profile. CONCLUSIONS: Differentiating depressive symptom profiles indicated that food-related behavioral interventions are most beneficial to alleviate somatic symptoms and symptoms of the atypical, energy-related profile linked to an immuno-metabolic form of depression, although effect sizes were small. Multi-nutrient supplements are not indicated to reduce depressive symptom profiles. These findings show that attention to clinical heterogeneity in depression is of importance when studying dietary interventions.

Metabolomic profiles discriminating anxiety from depression.

OBJECTIVE: Depression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations. METHODS: Data were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites. RESULTS: As compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration. CONCLUSION: While substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders.

Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses.

BACKGROUND: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease. METHODS: We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions. RESULTS: We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures. CONCLUSIONS: Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.

Medication Intake, Perceived Barriers, and Their Correlates Among Adults With Type 1 and Type 2 Diabetes: Results From Diabetes MILES - The Netherlands.

Purpose: The purpose of this study is to investigate medication intake, perceived barriers and their correlates in adults with type 1 or type 2 diabetes. Methods: In this cross-sectional study, 3,383 Dutch adults with diabetes (42% type 1; 58% type 2) completed the 12-item 'Adherence Starts with Knowledge' questionnaire (ASK-12; total score range: 12-60) and reported socio-demographics, clinical and psychological characteristics and health behaviors. Univariable and multivariable logistic regression analyses were used. Results: Adults with type 1 diabetes had a slightly lower mean ASK-12 score (i.e. more optimal medication intake and fewer perceived barriers) than adults with non-insulin-treated type 2 diabetes. After adjustment for covariates, correlates with suboptimal intake and barriers were fewer severe hypoglycemic events and more depressive symptoms and diabetes-specific distress. In type 2 diabetes, correlates were longer diabetes duration, more depressive symptoms and diabetes-specific distress. Conclusions: Adults with type 1 diabetes showed slightly more optimal medication intake and fewer perceived barriers than adults with non-insulin treated type 2 diabetes. Correlates differed only slightly between diabetes types. The strong association with depressive symptoms and diabetes-specific distress in both diabetes types warrants attention, as improving these outcomes in some people with diabetes might indirectly improve medication intake.

Associations of Non-Alcoholic Beverages with Major Depressive Disorder History and Depressive Symptoms Clusters in a Sample of Overweight Adults.

BACKGROUND: Meta-analysis of observational studies concluded that soft drinks may increase the risk of depression, while high consumption of coffee and tea may reduce the risk. Objectives were to explore the associations between the consumption of soft drinks, coffee or tea and: (1) a history of major depressive disorder (MDD) and (2) the severity of depressive symptoms clusters (mood, cognitive and somatic/vegetative symptoms). METHODS: Cross-sectional and longitudinal analysis based on baseline and 12-month-follow-up data collected from four countries participating in the European MooDFOOD prevention trial. In total, 941 overweight adults with subsyndromal depressive symptoms aged 18 to 75 years were analyzed. History of MDD, depressive symptoms and beverages intake were assessed. RESULTS: Sugar-sweetened soft drinks were positively related to MDD history rates whereas soft drinks with non-nutritive sweeteners were inversely related for the high vs. low categories of intake. Longitudinal analysis showed no significant associations between beverages and mood, cognitive and somatic/vegetative clusters. CONCLUSION: Our findings point toward a relationship between soft drinks and past MDD diagnoses depending on how they are sweetened while we found no association with coffee and tea. No significant effects were found between any studied beverages and the depressive symptoms clusters in a sample of overweight adults.

Acceptability and feasibility of two interventions in the MooDFOOD Trial: a food-related depression prevention randomised controlled trial in overweight adults with subsyndromal symptoms of depression.

OBJECTIVES: We report on the acceptability, feasibility, dose-response relationship and adherence of two nutritional strategies to improve mood (multinutrient supplements; food-related behavioural activation (F-BA)) studied in a randomised controlled depression prevention trial (the Multi-country cOllaborative project on the rOle of Diet, Food-related behaviour, and Obesity in the prevention of Depression (MooDFOOD) Trial). We also assessed baseline determinants of adherence and assessed whether better adherence resulted in lower depressive symptoms. DESIGN: Randomised controlled trial with a 2×2 factorial design conducted between 2015 and 2017. SETTING: Germany, the Netherlands, UK and Spain. PARTICIPANTS: Community sample of 1025 overweight adults with elevated depressive symptoms without a current episode of major depressive disorder. Main eligibility criteria included age (18-75 years), being overweight or obese, and having at least mild depressive symptoms, shown by a Patient Health Questionnaire Score of ≥5. A total of 76% of the sample was retained at the 12-month follow-up. INTERVENTIONS: Daily nutritional supplements versus pill placebo or an F-BA therapy, delivered in individual and group sessions versus no behavioural intervention over a 1-year period. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: self-reported acceptability of the interventions. SECONDARY OUTCOMES: adherence and self-reported depressive symptoms. RESULTS: Most participants reported that the F-BA was acceptable (83.61%), feasible to do (65.91%) and would recommend it to a friend (84.57%). Individual F-BA sessions (88.10%) were significantly more often rated as positive than group F-BA sessions (70.17%) and supplements (28.59%). There were statistically significant reductions in depressive symptoms for those who both adhered to the F-BA intervention and had a history of depression (B=-0.08, SE=0.03, p=0.012) versus those who had no history of depression. Supplement intake had no effect on depressive symptoms irrespective of adherence. CONCLUSIONS: F-BA may have scope for development as a depression prevention intervention and public health strategy but further refinement and testing are needed. TRIAL REGISTRATION NUMBER: NCT02529423.

Effects of food-related behavioral activation therapy on eating styles, diet quality and body weight change: Results from the MooDFOOD Randomized Clinical Trial.

OBJECTIVE: Depression and obesity are bi-directionally related, eating styles and diet quality are two important factors associated with both. It remains uncertain if and how these two factors can be modified. Therefore the current study aims to investigate whether food-related behavioral activation therapy (F-BA), targeting mood, dietary habits and food related behavior, can improve eating styles, and diet quality and reduce body weight in adults with overweight or obesity and subsyndromal depressive symptoms. METHODS: Data were derived from the MooDFOOD prevention trial, a 2x2 factorial RCT investigating the effect of nutritional strategies on prevention of depression. Changes in emotional, uncontrolled, and cognitive restrained eating (Three Factor Eating Questionnaire Revised), Mediterranean Diet Score (MDS), and body weight were analyzed among 1025 adults who either received F-BA or no intervention for 12 months. Intervention effect was tested by longitudinal analysis of covariance using mixed model analysis. RESULTS: The F-BA group showed a small decrease in emotional (ß=-5.68, p<.001) and uncontrolled eating (ß=-4.05, p=.03), and increase in cognitive restrained eating (ß=5.53, p<.01), compared to no F-BA. The effect of the F-BA therapy on emotional and uncontrolled eating was stronger in those with higher baseline depressive symptoms (IDS-SR). The F-BA did also lead to small improvements in MDS (ß=1.95, p<.001), but not to change in body weight. CONCLUSION: Our trial showed no reduction in bodyweight, but provides support for the possibility to improve both unhealthy eating styles and diet quality using an intervention targeting these specifically, although effects were small [Trial registration: clinicaltrials.gov NCT02529423].

Supplementation-induced increase in circulating omega-3 serum levels is not associated with a reduction in depressive symptoms: Results from the MooDFOOD depression prevention trial.

BACKGROUND: There is ambiguity on how omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with depression, and what the temporality of the association might be. The present study aimed to examine whether (intervention-induced changes in) n-3 PUFA levels were associated with (changes in) depressive symptoms. METHODS: Baseline, 6- and 12-month follow-up data on 682 overweight and subclinically depressed persons from four European countries that participated in the MooDFOOD depression prevention randomized controlled trial were used. Participants were allocated to four intervention groups: (a) placebos, (b) placebos and food-related behavioral activation therapy (F-BA), (c) multinutrient supplements (fish oil and multivitamin), and (d) multinutrient supplements and F-BA. Depressive symptoms were measured using the inventory of depressive symptomatology. PUFA levels (µmol/L) were measured using gas chromatography. Analyses were adjusted for sociodemographics, lifestyle, and somatic health. RESULTS: Increases in n-3 PUFA, docosahexaenoic acid, and eicosapentaenoic acid levels over time were significantly larger in the supplement groups than in placebo groups. Change in PUFA levels was not significantly associated with the change in depressive symptoms (ß = .002, SE = 0.003, p = .39; ß = .003, SE = 0.005, p = .64; ß = .005, SE = 0.005, p = .29; ß = -.0002, SE = 0.0004, p = .69). Baseline PUFA levels did not modify the intervention effects on depressive symptoms. CONCLUSIONS: In overweight and subclinical depressed persons, multinutrient supplements led to significant increases in n-3 PUFA levels over time, which were not associated with changes in depressive symptoms. Multinutrient supplements do not seem to be an effective preventive strategy in lowering depressive symptoms over time in these at-risk groups.

Depressive and anxiety symptoms and following of the Dutch Dietary Guidelines 2015 in adults with diabetes: Results from Diabetes MILES-The Netherlands.

OBJECTIVE: This study aims to examine the associations between following of the Dutch dietary guidelines 2015 and elevated depressive and anxiety symptoms in adults with diabetes. METHODS: Cross-sectional data of 3174 people (47% men, mean age 55 ± 14 years) with type 1 diabetes (n = 1369) and type 2 diabetes (n = 1805) participating in Diabetes MILES-The Netherlands were analysed. Following of the Dutch dietary guidelines 2015 was quantified using the Dutch Healthy Diet 2015 (DHD15)-index (12 food components; total score range 0-120 points), calculated from a 32-item food frequency questionnaire. Cases with elevated depressive and anxiety symptoms (cutoff ≥ 10) were measured using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Cox regression models were used to estimate the prevalence ratios (PRs) adjusted for demographical, lifestyle related, clinical and biomedical factors. RESULTS: Elevated depressive and anxiety symptoms were present in 167 (12%) and 89 (7%) of participants with type 1 diabetes and 215 (12%) and 97 (5%) of those with type 2 diabetes, respectively. In the total sample (n = 3174), a DHD15-index score in the highest quartile was associated with lower prevalence of elevated depressive symptoms, compared to the lowest quartile with an adjusted PR [95% CI] of 0.73 [0.55-0.98]. The inverse association was more pronounced among participants with type 2 diabetes and among non-smokers. There was no association with elevated anxiety symptoms (adjusted PR [95% CI]: 1.03 [0.68-1.55]). CONCLUSION: Closer following of the Dutch dietary guidelines 2015 was associated with a lower likelihood of elevated depressive symptoms in adults with type 2 diabetes.

Bidirectional longitudinal associations of omega-3 polyunsaturated fatty acid plasma levels with depressive disorders.

BACKGROUND: Temporality of the association of low omega-3 polyunsaturated fatty acid (n-3 PUFA) plasma levels with depression remains questionable. To determine the underlying nature of these associations, this study examined the bidirectional longitudinal associations of n-3 PUFA plasma levels with (presence, onset and course of) depressive disorders and symptoms. METHODS: Baseline (n = 2912, 28.6% with current depressive disorder) and 6-year follow-up data (n = 1966, 13.0% with current depressive disorder) of the Netherlands Study of Depression and Anxiety (NESDA) were used. Depression diagnoses and symptoms were based on psychiatric interviews and self-report questionnaires. N-3 PUFA levels (ratio of total fatty acids (mmol%)), were assessed using nuclear magnetic resonance. RESULTS: Using two waves of data, n-3 PUFA levels were lower among depressed persons, as compared to healthy controls (Beta = -0.047, SE = 0.011, p < .001). Nevertheless, baseline n-3 PUFA levels were not consistently associated with subsequent change in depressive symptoms, onset or remission of depressive disorders over 6 years. Furthermore, the difference in n-3 PUFA levels detected at baseline between depressed and non-depressed participants tended to dissipate over 6 years (depression-by-time estimate: p = .011). Finally, subjects depressed both at baseline and at 6-year follow up had consistently lower n-3 PUFA levels over the entire follow-up as compared to those who had never been depressed. Change in depressive disorders across waves was not consistently accompanied by change in n-3 PUFA levels over time. LIMITATIONS: No data on intermediate time points and EPA levels were available. CONCLUSIONS: Despite significant cross-sectional associations between n-3 PUFA plasma levels and depressive disorders and severity, this 6-year longitudinal study could not confirm an uni- or bidirectional association over time. The association between depression and n-3 PUFA plasma levels is unlikely to be causal.

Measurement and genetic architecture of lifetime depression in the Netherlands as assessed by LIDAS (Lifetime Depression Assessment Self-report).

BACKGROUND: Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression. METHODS: Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n ≈ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS). RESULTS: Estimates of current and lifetime MDD prevalence were 6.7% and 18.1%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95% CI 1.15-1.32, R2 = 1.47%). CONCLUSIONS: By assessing MDD status in the Netherlands using the LIDAS instrument, we were able to confirm previously reported MDD prevalence and heritability estimates, which suggests that this instrument can be used in epidemiological and genetic association studies of depression.

Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas.

Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug-metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug-metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/).