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      Genetic determinants of depression: recent findings and future directions.

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          Abstract

          After participating in this activity, learners should be better able to: 1. Evaluate current evidence regarding the genetic determinants of depression 2. Assess findings from studies of gene-environment interaction 3. Identify challenges to gene discovery in depression Depression is one of the most prevalent, disabling, and costly mental health conditions in the United States and also worldwide. One promising avenue for preventing depression and informing its clinical treatment lies in uncovering the genetic and environmental determinants of the disorder as well as their interaction (G × E). The overarching goal of this review article is to translate recent findings from studies of genetic association and G × E related to depression, particularly for readers without in-depth knowledge of genetics or genetic methods. The review is organized into three major sections. In the first, we summarize what is currently known about the genetic determinants of depression, focusing on findings from genome-wide association studies (GWAS). In the second section, we review findings from studies of G × E, which seek to simultaneously examine the role of genes and exposure to specific environments or experiences in the etiology of depression. In the third section, we describe the challenges to genetic discovery in depression and promising strategies for future progress.

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          Most cited references93

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            Genome-wide association studies for complex traits: consensus, uncertainty and challenges.

            The past year has witnessed substantial advances in understanding the genetic basis of many common phenotypes of biomedical importance. These advances have been the result of systematic, well-powered, genome-wide surveys exploring the relationships between common sequence variation and disease predisposition. This approach has revealed over 50 disease-susceptibility loci and has provided insights into the allelic architecture of multifactorial traits. At the same time, much has been learned about the successful prosecution of association studies on such a scale. This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.
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              Cognition and depression: current status and future directions.

              Cognitive theories of depression posit that people's thoughts, inferences, attitudes, and interpretations, and the way in which they attend to and recall information, can increase their risk for depression. Three mechanisms have been implicated in the relation between biased cognitive processing and the dysregulation of emotion in depression: inhibitory processes and deficits in working memory, ruminative responses to negative mood states and negative life events, and the inability to use positive and rewarding stimuli to regulate negative mood. In this review, we present a contemporary characterization of depressive cognition and discuss how different cognitive processes are related not only to each other, but also to emotion dysregulation, the hallmark feature of depression. We conclude that depression is characterized by increased elaboration of negative information, by difficulties disengaging from negative material, and by deficits in cognitive control when processing negative information. We discuss treatment implications of these conclusions and argue that the study of cognitive aspects of depression must be broadened by investigating neural and genetic factors that are related to cognitive dysfunction in this disorder. Such integrative investigations should help us gain a more comprehensive understanding of how cognitive and biological factors interact to affect the onset, maintenance, and course of depression.
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                Author and article information

                Journal
                Harv Rev Psychiatry
                Harvard review of psychiatry
                Ovid Technologies (Wolters Kluwer Health)
                1465-7309
                1067-3229
                January 8 2015
                : 23
                : 1
                Affiliations
                [1 ] From the Department of Psychiatry, Harvard Medical School (Drs. Dunn and Smoller); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (Drs. Dunn, Rosand, and Smoller, and Ms. Dai); Stanley Center for Psychiatric Research (Drs. Dunn and Smoller) and Program in Medical and Population Genetics (Dr. Rosand), Broad Institute of Harvard and MIT, Cambridge, MA; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University (Drs. Brown and Amstadter); Department of Neurology, Massachusetts General Hospital, Boston, MA (Dr. Rosand); Department of Psychiatry and Human Behavior, Alpert Brown Medical School (Dr. Nugent); Center on the Developing Child, Harvard University (Dr. Smoller).
                Article
                00023727-201501000-00001 NIHMS645804
                10.1097/HRP.0000000000000054
                4309382
                25563565
                6aab3d28-d2a4-46d6-b218-586397879b27
                History

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