Depression Treatment: Genetic Predictors of Response to Serotonergic and Noradrenergic Antidepressants in Major Depressive Disorder: A Genome-Wide Analysis of Individual-Level Data and a Meta-Analysis.

Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

Filed under: Depression Treatment

PLoS Med. 2012 Oct; 9(10): e1001326
Tansey KE, Guipponi M, Perroud N, Bondolfi G, Domenici E, Evans D, Hall SK, Hauser J, Henigsberg N, Hu X, Jerman B, Maier W, Mors O, O’Donovan M, Peters TJ, Placentino A, Rietschel M, Souery D, Aitchison KJ, Craig I, Farmer A, Wendland JR, Malafosse A, Holmans P, Lewis G, Lewis CM, Stensbøl TB, Kapur S, McGuffin P, Uher R

It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8)). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8)) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary. HubMed – depression


Sleep quality, depression, and quality of life in elderly hemodialysis patients.

Filed under: Depression Treatment

Int J Nephrol Renovasc Dis. 2012; 5: 135-42
Turkmen K, Erdur FM, Guney I, Gaipov A, Turgut F, Altintepe L, Saglam M, Tonbul HZ, Abdel-Rahman EM

Both the incidence and the prevalence of end-stage renal disease (ESRD) in elderly patients are increasing worldwide. Elderly ESRD patients have been found to be more prone to depression than the general population. There are many studies that have addressed the relationship between sleep quality (SQ), depression, and health related quality of life (HRQoL) in ESRD patients, but previous studies have not confirmed the association in elderly hemodialysis (HD) patients. Therefore, the aim of the present study was to demonstrate this relationship in elderly HD patients.Sixty-three elderly HD patients (32 females and 31 males aged between 65 and 89 years) were included in this cross-sectional study. A modified Post-Sleep Inventory (PSI), the Medical Outcomes Study 36-item short form health survey, and the Beck Depression Inventory (BDI) were applied.The prevalence of poor sleepers (those with a PSI total sleep score [PSI-4 score] of 4 or higher) was 71% (45/63), and the prevalence of depression was 25% (16/63). Of the 45 poor sleepers, 15 had depression, defined as a BDI score of 17 or higher. Poor sleepers had a significantly higher rate of diabetes mellitus (P = 0.03), significantly higher total BDI scores, and lower Physical Component Scale scores (ie, lower HRQoL) than good sleepers. The PSI-4 score correlated negatively with Physical Component Scale (r = -0.500, P < 0.001) and Mental Component Scale scores (r = -0.527, P < 0.001) and it correlated positively with the BDI score (r = 0.606, P < 0.001). In multivariate analysis, independent variables of PSI-4 score were BDI score (beta value [?] = 0.350, P < 0.001), Mental Component Scale score (? = -0.291, P < 0.001), and age (? = 0.114, P = 0.035).Poor SQ is a very common issue and is associated with both depression and lower HRQoL in elderly HD patients. HubMed – depression


Heterozygosity-Fitness Correlations in Adult and Juvenile Zenaida Dove, Zenaida aurita.

Filed under: Depression Treatment

J Hered. 2012 Oct 22;
Monceau K, Wattier R, Dechaume-Moncharmont FX, Dubreuil C, Cézilly F

Understanding how fitness is related to genetic variation is of crucial importance in both evolutionary ecology and conservation biology. We report a study of heterozygosity-fitness correlations in a wild, noninbred population of Zenaida Doves, Zenaida aurita, based on a sample comprising 489 individuals (382 adults and 107 juveniles) typed at 13 microsatellite loci, resulting in a data set comprising 5793 genotypes. In both adults and juveniles, and irrespective of sex, no evidence was found for an effect of either multilocus or single-locus heterozygosity on traits potentially related to fitness such as foraging tactic, competitive ability, and fluctuating asymmetry. In contrast, a significant negative correlation between body condition and multilocus heterozygosity, indicative of outbreeding depression, was found in juveniles, whereas no such trend was observed in adults. However, the frequency distribution of heterozygosity did not differ between the two age classes, suggesting compensatory growth by heterozygous juveniles. We discuss our results in relation to some practical limitations associated with studies of heterozygosity-fitness correlations, and suggest that tropical bird species with allopatric divergence between island populations may provide a good biological model for the detection of outbreeding depression.
HubMed – depression



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