Number of risk genotypes is a risk factor for major depressive disorder: a case control study

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dc.contributor.author Holly Garriock en_US
dc.contributor.author Pedro Delgado en_US
dc.contributor.author Mitchel Kling en_US
dc.contributor.author Linda Carpenter en_US
dc.contributor.author Michael Burke en_US
dc.contributor.author William Burke en_US
dc.contributor.author Thomas Schwartz en_US
dc.contributor.author Lauren Marangell en_US
dc.contributor.author Mustafa Husain en_US
dc.contributor.author Robert Erickson en_US
dc.contributor.author Francisco Moreno en_US
dc.date.accessioned 2009-05-05T16:15:49Z
dc.date.available 2006 - en_US
dc.date.available 2009-05-05T16:15:49Z
dc.date.issued 2007-10-31 en_US
dc.identifier.citation Holly Garriock;Pedro Delgado;Mitchel Kling;Linda Carpenter;Michael Burke;William Burke;Thomas Schwartz;Lauren Marangell;Mustafa Husain;Robert Erickson;Francisco Moreno: Number of risk genotypes is a risk factor for major depressive disorder: a case control study. Behavioral and Brain Functions 2006, 2(1):24. en_US
dc.identifier.uri http://www.behavioralandbrainfunctions.com/content/2/1/24 en_US
dc.identifier.uri http://hdl.handle.net/2271/613
dc.description.abstract BACKGROUND:The objective of the study was to determine the genetic basis of Major Depressive Disorder, and the capacity to respond to antidepressant treatment. An association study of 21 candidate polymorphisms relevant to monoamine function and the mechanism of antidepressant response was conducted in 3 phenotypically distinct samples: a group with chronic or recurrent depression unable to respond to antidepressants (non-responders) (n = 58), a group capable of symptomatic improvement with or without treatment (responders) (n = 39), and volunteer controls (n = 85). The responders and non-responders constituted a larger group of depressed subjects.METHODS:A candidate gene approach was employed to asses the genetics basis of Major Depressive Disorder. The genotypic frequencies of selected polymorphisms were compared between the controls and depressed subjects. To asses the genetics basis of the capacity to respond to antidepressant treatment, the responders were compared to the non-responders. Candidate genes were chosen based on functional studies and proximity to whole genome linkage findings in the literature. Risk genotypes were identified by previous functional studies and association studies.RESULTS:A statistically significant difference in genotype frequency for the SLC6A4 intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). Surprisingly, a statistically significant difference was detected between responders and non-responders for the DRD4 exon III VNTR genotype frequencies (p = 0.009). Furthermore, a difference between the controls and depressed subjects as well as between the controls and non-responders was detected for the number and distribution of risk genotypes in each group.CONCLUSION:An association between several monoamine-related genes and Major Depressive Disorder is supported. The data suggest that the two depressive phenotypes are genetically different, inferring that the genetic basis for the capacity to respond to standard antidepressant treatment, and the genetic susceptibility to Major Depressive Disorder may be independent. In addition, a proof of concept is provided demonstrating that the number of risk genotypes may be an indication of susceptibility of major depressive disorder and the severity of the disorder. en_US
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dc.format.mimetype application/pdf
dc.format.mimetype text/plain
dc.format.mimetype application/octet-stream
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dc.language en en_US
dc.language.iso en_US
dc.publisher BioMedCentral en_US
dc.relation.ispartof 1744-9081 en_US
dc.relation.hasversion http://www.biomedcentral.com/content/pdf/1744-9081-2-24.pdf en_US
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.subject.mesh Analysis of Variance en_US
dc.subject.mesh Animals en_US
dc.subject.mesh Behavior, Animal en_US
dc.subject.mesh Brain-Derived Neurotrophic Factor/genetics/ metabolism en_US
dc.subject.mesh CREB-Binding Protein/metabolism en_US
dc.subject.mesh Extracellular Signal-Regulated MAP Kinases/metabolism en_US
dc.subject.mesh Freund's Adjuvant en_US
dc.subject.mesh Functional Laterality en_US
dc.subject.mesh Gene Expression Regulation/drug effects/ physiology en_US
dc.subject.mesh Hippocampus/ metabolism en_US
dc.subject.mesh Inflammation/chemically induced/complications en_US
dc.subject.mesh Male en_US
dc.subject.mesh Pain/etiology/ pathology en_US
dc.subject.mesh RNA, Messenger/metabolism en_US
dc.subject.mesh Rats en_US
dc.subject.mesh Rats, Sprague-Dawley en_US
dc.subject.mesh Receptors, Neurokinin-1/genetics/ metabolism en_US
dc.subject.mesh Spinal Cord/ metabolism en_US
dc.subject.mesh Time Factors en_US
dc.title Number of risk genotypes is a risk factor for major depressive disorder: a case control study en_US
dc.type article en_US
dc.date.captured 2009-04-27 en_US
dc.identifier.doi doi:10.1186/1744-9081-2-24 en_US
dc.identifier.pmid 17974009 en_US

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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