Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies

Shyn, Stanley I.; Shi, Jianxin; Kraft, Jeffrey B.; Potash, James B.; Knowles, James A.; Weissman, Myrna M.; Garriock, Holly A.; Yokoyama, Jennifer S.; McGrath, Patrick J.; Peters, Eric; Scheftner, William A.; Coryell, William; Lawson, William B.; Jancic, Dubravka; Gejman, Pablo V.; Sanders, Alan R.; Holmans, Peter Alan; Slager, Susan L.; Levinson, Douglas F.; Hamilton, Steven P.

doi:10.1038/mp.2009.125

Cited by 241 publications

(181 citation statements)

References 61 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…However, this finding was not replicated by Shyn et al on a different cohort of European ancestry [37]. Differences in inclusion criteria may be crucial in these different findings.…”

Section: Genetic Techniques To Detect Variantscontrasting

confidence: 51%

The Genetics of MDD – A Review of Challenges and Opportunities

Heutink¹

2014

J Depress Anxiety

View full text Add to dashboard Cite

Abstract:Major depressive disorder (MDD) is a psychiatric disorder characterized among others by prolonged depressed mood, a loss of interest in enjoyable activities, psychomotor retardation and various cognitive symptoms. Although exact numbers of prevalence may differ between various western countries, partly due to a social taboo of the illness, the life-time prevalence in the USA and Western Europe lies around 15%. Women are more likely to be struck by MDD than men, often with a first episode between 30-40 years of age, with a smaller second peak around 50-60 years of age. Although MDD may appear as a "stand alone" disease, 33% of patients with a chronic illness report symptoms of major depression. In addition, approximately 72% of patients diagnosed with MDD also have a second mental illness diagnosed, in most cases generalized anxiety disorder or a social phobia. Although some patients may only experience a single episode, MDD often appears in multiple episodes.

show abstract

“…However, this finding was not replicated by Shyn et al on a different cohort of European ancestry [37]. Differences in inclusion criteria may be crucial in these different findings.…”

Section: Genetic Techniques To Detect Variantscontrasting

confidence: 51%

The Genetics of MDD – A Review of Challenges and Opportunities

Heutink¹

2014

J Depress Anxiety

View full text Add to dashboard Cite

show abstract

“…Indeed, genome‐wide association studies (GWAS) have shown that these disorders are highly polygenic (Barnett & Smoller, 2009; Schizophrenia Working Group of the Psychiatric Genomics, 2014; Shyn et al., 2011) with many genes exerting their influence on numerous neural pathways involved in complex aspects of brain function and likely being impacted upon by environmental events. It has been proposed that individual vulnerability and sensitization to the later development of mental health disorders may partly be regulated through variation in genes encoding proteins that impact on neurotransmitter and hormone systems such as those involved in dopamine, serotonin, and cortisol function (Caspi & Moffitt, 2006; Collip, Myin‐Germeys, & Van Os, 2008; van Winkel, Stefanis, & Myin‐Germeys, 2008; van Winkel, van Nierop, Myin‐Germeys, & van Os, 2013).…”

Section: Introductionmentioning

confidence: 99%

The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

et al. 2017

View full text Add to dashboard Cite

IntroductionPrevious research has indicated that variation in genes encoding catechol‐O‐methyltransferase (COMT) and dopamine receptor D2 (DRD2) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia. However, increasing evidence suggests environmental factors such as early life stress may interact with genetic variants in affecting these cognitive outcomes. This study investigated the effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress in healthy adults.MethodsOne hundred and twenty‐two healthy adult males (mean age 35.2 years, range 21–63) were enrolled in the study. Cognitive function was assessed using Cambridge Neuropsychological Test Automated Battery and early life stress was assessed using the Childhood Traumatic Events Scale (Pennebaker & Susman, 1988).Results DRD2 C957T was significantly associated with executive function, with CC homozygotes having significantly reduced performance in spatial working memory and spatial planning. A significant genotype–trauma interaction was found in Rapid Visual Information Processing test, a measure of sustained attention, with CC carriers who had experienced early life stress exhibiting impaired performance compared to the CC carriers without early life stressful experiences. There were no significant findings for COMT Val158Met.ConclusionsThis study supports previous findings that DRD2 C957T significantly affects performance on executive function related tasks in healthy individuals and shows for the first time that some of these effects may be mediated through the impact of childhood traumatic events. Future work should aim to clarify further the effect of stress on neuronal systems that are known to be vulnerable in mental health disorders and more specifically what the impact of this might be on cognitive function.

show abstract

“…Indeed, a number of large genome-wide association studies, and some subsequent meta-analyses, have identified genetic polymorphisms associated with both risk of depression [71][72][73] and response to antidepressant therapy. 74,75 However, these studies have been unable to demonstrate consistent and reproducible genetic associations.…”

Section: Folate Depression and Geneticsmentioning

confidence: 99%