Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies

Abstract

Background Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. Method We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20-or 10-item CES-D scale (32 528 persons). Results One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery +replication = 1.10 × 10−6) with evidence of heterogeneity. Conclusions Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

REM sleep fragmentation associated with depressive symptoms and genetic risk for depression in a community-based sample of adolescents

“…However, due to the logistical difficulties inherent in assessing sleep architecture in large samples of adolescents, data on the link between depressive symptoms and REM fragmentation are scarce. The current study explored how REM sleep fragmentation, density, and latency are related to self-reported depressive symptoms and to a genetic predisposition to depression, using an adolescent birth cohort and a polygenic risk score (PRS) derived from a recent genome-wide association study (GWAS) for depressive symptoms (Demirkan et al 2016).…”

“…We performed a weighted polygenic risk score (PRS) analysis using betas from GWAS summary statistics data of CHARGE Consortium GWAS for dimensions of depressive symptoms (Demirkan et al 2016). The dimensions were three subscales from The Center for Epidemiologic Studies Depression Scale (CES-D), namely negative emotion, lack of positive emotion, and somatic complaints.…”

“…We also examined whether the effect of depressive symptoms on REM sleep would be enhanced by genetic vulnerability to depression. Towards this aim, we built a polygenic risk score (PRS) derived from a recent genome-wide association study (GWAS) for depressive symptoms (Demirkan et al 2016). The asset in polygenic scores is that they combine together many genetic variants obtained from large, already existing genome-wide association studies.…”

The intergenerational production of depression in South Korea: results from a cross-sectional study

“…The CES-D scale was developed to diagnose depression by way of assessing a range of depressive symptoms. This scale is a widely used measure of depression and several short CES-D forms have been developed from it [30, 31]. Each item was answered using a 4-point scale (0 = less than one day in the past week; 1 = two or three days in the past week; 2 = four or five days in the past week; 3 = six or seven days in the past week).…”

Genetic basis of depressive disorders

“…According to the subsequent genome-wide association studies, SNPs residing the genes involved in circadian rhythms regulation such as sirtuin 1 (SIRT1), melatonin receptor 1A gene (MTNR1A), fragile histidine triad (FHIT) (CONVERGE consortium, 2015;Demirkan et al, 2016;Direk et al, 2017) are of interest. These findings suggest a significant role of circadian rhythms in the regulation of individual psychoemotional sphere and point to the necessity to consider them in the DD research for the understanding of biological mechanisms causing this affective disorder.…”