The efficacy of fish oil supplements in the treatment of depression: food for thought.

A recent meta-analysis and meta-regression of 13 randomized clinical trials by Mocking et al.1 concluded that supplementation with omega-3 fatty acids, found naturally in fatty fish, has a beneficial effect in patients with major depressive disorder (MDD), especially for higher doses of the eicosapentaenoic acid (EPA) and in patients taking antidepressants. Novel treatments for MDD are certainly desired. However, in our view the evidence in this study does not solve the academic debate on the efficacy of omega-3 fatty acids for MDD. Some food for thought

Association between adolescent oral contraceptive use and future major depressive disorder: a prospective cohort study

Background Because of the widespread use of oral contraceptives (OCs) and the devastating effects of depression both on an individual and a societal level, it is crucial to understand the nature of the previously reported relationship between OC use and depression risk. Insight into the impact of analytical choices on the association is important when interpreting available evidence. Hence, we examined the association between adolescent OC use and subsequent depression risk in early adulthood analyzing all theoretically justifiable models. Methods Data from the prospective cohort study TRacking Adolescents' Individual Lives Survey, among women aged 13-25 years were used. Adolescent OC use (ages 16-19 years) was used as a predictor and major depressive disorder (MDD) in early adulthood (ages 20-25 years), as assessed by the Diagnostic and Statistical Manual of Mental Disorders-IV oriented Lifetime Depression Assessment Self-Report and the Composite International Diagnostic Interview, was used as an outcome. A total of 818 analytical models were analyzed using Specification Curve Analysis in 534 adolescent OC users and 191 nonusers. Results Overall, there was an association of adolescent OC use and an episode of MDD in early adulthood [median odds ratio (OR)(median) = 1.41; ORmin = 1.08; ORmax = 2.18, p < .001], which was driven by the group of young women with no history of MDD (ORmedian = 1.72; ORmin = 1.21; ORmax = 2.18, p < .001). Conclusions In summary, adolescent OC use was associated with a small but robust increased risk for experiencing an episode of MDD, especially among women with no history of MDD in adolescence. Understanding the potential side effects of OCs will help women and their doctors to make informed choices when deciding among possible methods of birth control

Bayesian evidence synthesis in case of multi-cohort datasets: An illustration by multi-informant differences in self-control

The trend toward large-scale collaborative studies gives rise to the challenge of combining data from different sources efficiently. Here, we demonstrate how Bayesian evidence synthesis can be used to quantify and compare support for competing hypotheses and to aggregate this support over studies. We applied this method to study the ordering of multi-informant scores on the ASEBA Self Control Scale (ASCS), employing a multi-cohort design with data from four Dutch cohorts. Self-control reports were collected from mothers, fathers, teachers and children themselves. The available set of reporters differed between cohorts, so in each cohort varying components of the overarching hypotheses were evaluated. We found consistent support for the partial hypothesis that parents reported more self-control problems than teachers. Furthermore, the aggregated results indicate most support for the combined hypothesis that children report most problem behaviors, followed by their mothers and fathers, and that teachers report the fewest problems. However, there was considerable inconsistency across cohorts regarding the rank order of children's reports. This article illustrates Bayesian evidence synthesis as a method when some of the cohorts only have data to ev

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197

Childhood abuse v. neglect and risk for major psychiatric disorders

Background Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders. Methods Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473). Results Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17-5.67) and neglect for BD (OR 2.69, 95% CI 2.09-3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55-3.01) and suicide attempts (OR 2.16, 95% CI 1.55-3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02-1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08-2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01-0.24). Conclusions Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

Background So far, more than 170 loci have been associated with circulating lipid levels through genomewide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ~60 000 individuals in the discovery stage and ~90 000 samples in the replication stage. Results Our study resu

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

HapMap imputed genome-wide association studies (GWAS) have revealed &gt;50 loci at which common variants with minor allele frequency &gt;5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value &lt; 5 × 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR &lt; 0.05) genes and 127 significantly (FDR &lt; 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples

ein Rückblick auf meine Mitarbeit im Gebiete der Sprach- und Religionswissenschaft

Digitalisat der Ausgabe von 1927, erschienen 201